Biology, Volume 13, Issue 5 (May 2024) – 37 articles

Hyaluronic acid (HA) is a new functional food additive which has the potential to ameliorate persistent inflammation, immunosuppression and catabolism syndrome (PICS), but the biological effects of HA with various molecular weights differ dramatically. To systematically investigate the efficacy of HA in altering PICS symptoms, medium-molecular-weight (MMW) HA was specifically selected to test its intervention effect on a PICS mouse model induced by CLP through oral administration, with high-molecular-weight (HMW) and low-molecular-weight (LMW) HA also participating in the experimental validation process. The results of pathological observations and gut flora showed that MMW HA rapidly alleviated lung lesions and intestinal structural changes in PICS mice in the short term. However, although long-term MMW HA administration significantly reduced the proportions of harmful bacteria in gut flora, inflammatory responses in the intestines and lungs of PICS mice were significantly higher in the MMW HA group than in the HMW HA and LMW HA groups. The use of HMW HA not only rapidly reduced the mortality rate of PICS mice but also improved their grip strength and the recovery of spleen and thymus indices. Furthermore, it consistently promoted the recovery of lung and intestinal tissues in PICS mice, and it also assisted in the sustained restoration of their gut microbiota. These effects were superior to those of LMW HA and MMW HA. The experimental results indicate that HMW weight HA has the greatest potential to be an adjunct in alleviating PICS as a food additive, while the safety of other HAs requires further attention. Full article

P. euphratica stands as the pioneering and dominant tree within desert riparian forests in arid and semi-arid regions. The aim of our work was to reveal why dioecious P. euphratica in natural desert riparian forests in the lower Tarim River exhibits sexual spatial distribution differences combined with field investigation, tree ring techniques, isotope analysis techniques, and statistical analyses. The results showed that P. euphratica was a male-biased population, with the operational sex ratio (OSR) exhibiting spatial distribution differences to variations in drought stress resulting from groundwater depth change. The highest OSR was observed under mild drought stress (groundwater depth of 6–7 m), and it was reduced under non-drought stress (groundwater depth below 6 m) or severe drought stress (groundwater depth exceeding 7 m). As drought stress escalated, the degradation and aging of the P. euphratica forest became more pronounced. Males exhibited significantly higher growth rates and WUE_i than females under mild drought stress. However, under severe drought stress, males’ growth rates significantly slowed down, accompanied by significantly lower WUE_i than in females. This divergence determined the sexual spatial segregation of P. euphratica in the natural desert riparian forests of the lower Tarim River. Furthermore, the current ecological water conveyance project (EWCP) in the lower Tarim River was hard to fundamentally reverse the degradation and aging of the P. euphratica forest due to inadequate population regeneration. Consequently, we advocated for an optimized ecological water conveyance mode to restore, conserve, and rejuvenate natural P. euphratica forests. Full article

In this study, a commercial sodium butyrate protected by a new buffer salt solution (NSB) was tested to determine whether it can be used as an antibiotic alternative in broiler production. A total of 192 1-day-old broilers were randomly allocated to three dietary treatments: soybean meal diet (CON), antibiotic diet (ANT, basal diet + 100 mg/kg aureomycin), and NSB (basal diet + 800 mg/kg NSB). The growth performance, serum anti-inflammatory cytokines, intestinal morphology, gut barrier function, antioxidative parameters, SCFAs’ content, and cecal microbiota were analyzed. The result showed that NSB significantly improved ADFI and ADG (p < 0.01), and decreased FCR (p < 0.01). Serum anti-inflammatory cytokine IL-10 was up-regulated (p < 0.01), and pro-inflammatory TNF-α was down-regulated (p < 0.05) by NSB supplementation. H&E results showed that VH and the VH/CD ratio significantly increased (p < 0.05) in the jejunum and ileum in the NSB group. Furthermore, ZO-1 (p < 0.01), claudin-1 (p < 0.01), and occludin (p < 0.05) in the jejunum and claudin-1 (p < 0.01) and mucin-2 (p < 0.05) in the ileum were significantly up-regulated in the NSB group. Additionally, SOD (p < 0.05) and the T-AOC/MDA ratio (p < 0.01) in the jejunum and SOD in the ileum were significantly increased (p < 0.05) in the NSB group. The MDA level also significantly increased (p < 0.01) in the ANT group in the jejunum. Propionic acid (p < 0.05) and butyric acid (p < 0.01) content significantly increased in the NSB group in the jejunum and ileum segments. The 16S rRNA sequencing results showed no significant difference (p > 0.05) in alpha and beta diversity among the groups. LEFSe analysis also indicated that Peptostreptococcaceae, Colidextribacter, Firmicutes, Oscillospira, and Erysipelatoclostridiaceae, which promote SCFA production (p < 0.05), were identified as dominant taxon-enriched bacterial genera in the NSB group. The Spearman correlation analysis revealed that Colidextribacter with ADFI, ADG, VH, claudin-1 (p < 0.05), and unclassified_f__Peptostreptococcaceae with ADFI, IL-10, and ZO-1 were positively correlated (p < 0.05). Furthermore, ADFI and ADG with IL-10, claudin-1, SOD, T-AOC, and butyric acid (p < 0.05), and similarly, ADG with VH (p < 0.05), showed a positive correlation. In conclusion, NSB enhanced the growth performance by improving jejunum and ileum morphology, and serum anti-inflammatory cytokines, and by regulating the intestinal barrier function and antioxidant capacity, SCFAs’ content, and cecum microbiota, showing its potential use as an alternative to antibiotics in poultry nutrition. Full article

Serbia has recently begun facing a serious problem with the Brown Marmorated Stink Bug, Halyomorpha halys (Stål), which was first recorded in October 2015. This species belongs to the Pentomidae family and is notorious for causing extensive damage to plants. During the winter, it tends to gather in urban areas, such as houses and different man-made facilities, which has raised concerns among producers and citizens. The population of this species has rapidly increased, causing significant economic damage to cultivated plants. However, despite the alarming situation no natural enemies have yet been identified in Serbia. Therefore, research in 2022 was focused on collecting stink bug eggs to investigate the presence of egg parasitoids. The study identified two foreign Hymenoptera species for the European region, Trissolcus japonicus (Ashmead) and Tr. mitsukurii (Ashmead) (Scelionidae), recorded for the first time in Serbia. Additionally, the list of egg parasitoid species belonging to the Hymenoptera order includes seven local species: Anastatus bifasciatus (Geoffroy), from the Eupelmidae family; Ooencyrtus sp., from the Encyrtidae family; and Telenomus turesis (Walker), Tr. basalis (Wollaston), Tr. belenus (Walker), Tr. colemani (Crawford), and Tr. semistriatus (Nees von Esenbeck), from the Scelionidae family. In total, nine egg parasitoid species were, for the first time, reported as parasitizing H. halys and related species in Serbia. Full article

Traditional treatments of cancer have faced various challenges, including toxicity, medication resistance, and financial burdens. On the other hand, bioactive phytochemicals employed in complementary alternative medicine have recently gained interest due to their ability to control a wide range of molecular pathways while being less harmful. As a result, we used a network pharmacology approach to study the possible regulatory mechanisms of active constituents of Cordia myxa for the treatment of liver cancer (LC). Active constituents were retrieved from the IMPPAT database and the literature review, and their targets were retrieved from the STITCH and Swiss Target Prediction databases. LC-related targets were retrieved from expression datasets (GSE39791, GSE76427, GSE22058, GSE87630, and GSE112790) through gene expression omnibus (GEO). The DAVID Gene Ontology (GO) database was used to annotate target proteins, while the Kyoto Encyclopedia and Genome Database (KEGG) was used to analyze signaling pathway enrichment. STRING and Cytoscape were used to create protein–protein interaction networks (PPI), while the degree scoring algorithm of CytoHubba was used to identify hub genes. The GEPIA2 server was used for survival analysis, and PyRx was used for molecular docking analysis. Survival and network analysis revealed that five genes named heat shot protein 90 AA1 (HSP90AA1), estrogen receptor 1 (ESR1), cytochrome P450 3A4 (CYP3A4), cyclin-dependent kinase 1 (CDK1), and matrix metalloproteinase-9 (MMP9) are linked with the survival of LC patients. Finally, we conclude that four extremely active ingredients, namely cosmosiin, rosmarinic acid, quercetin, and rubinin influence the expression of HSP90AA1, which may serve as a potential therapeutic target for LC. These results were further validated by molecular dynamics simulation analysis, which predicted the complexes with highly stable dynamics. The residues of the targeted protein showed a highly stable nature except for the N-terminal domain without affecting the drug binding. An integrated network pharmacology and docking study demonstrated that C. myxa had a promising preventative effect on LC by working on cancer-related signaling pathways. Full article

Escherichia coli (E. coli) is a frequent gram-negative bacterium that causes nosocomial infections, affecting more than 100 million patients annually worldwide. Bacterial lipopolysaccharide (LPS) from E. coli binds to toll-like receptor 4 (TLR4) and its co-receptor’s cluster of differentiation protein 14 (CD14) and myeloid differentiation factor 2 (MD2), collectively known as the LPS receptor complex. LPCAT2 participates in lipid-raft assembly by phospholipid remodelling. Previous research has proven that LPCAT2 co-localises in lipid rafts with TLR4 and regulates macrophage inflammatory response. However, no published evidence exists of the influence of LPCAT2 on the gene expression of the LPS receptor complex induced by smooth or rough bacterial serotypes. We used RAW264.7—a commonly used experimental murine macrophage model—to study the effects of LPCAT2 on the LPS receptor complex by transiently silencing the LPCAT2 gene, infecting the macrophages with either smooth or rough LPS, and quantifying gene expression. LPCAT2 only significantly affected the gene expression of the LPS receptor complex in macrophages infected with smooth LPS. This study provides novel evidence that the influence of LPCAT2 on macrophage inflammatory response to bacterial infection depends on the LPS serotype, and it supports previous evidence that LPCAT2 regulates inflammatory response by modulating protein translocation to lipid rafts. Full article

Mycobacterium tuberculosis (Mtb) ranks as the most lethal human pathogen, able to fend off repeated attacks by the immune system or medications. PE_PGRS proteins are hallmarks of the pathogenicity of Mtb and contribute to its antigenic diversity, virulence, and persistence during infection. M. smegmatis is a nonpathogenic mycobacterium that naturally lacks PE_PGRS and is used as a model to express Mtb proteins. PE_PGRS has the capability to evade host immune responses and enhance the intracellular survival of M. smegmatis. Despite the intense investigations into PE_PGRS proteins, their role in tuberculosis remains elusive. We engineered the recombinant M. smegmatis strain Ms-PE_PGRS38. The result shows that PE_PGRS38 is expressed in the cell wall of M. smegmatis. PE_PGRS38 contributes to biofilm formation, confers permeability to the cell wall, and shows variable responses to exogenous stresses. PE_PGRS38 downregulated TLR4/NF-κB signaling in RAW264.7 macrophages and lung tissues of infected mice. In addition, PE_PGRS38 decreased NLRP3-dependent IL-1β release and limited pathogen-mediated inflammasome activity during infection. Moreover, PE_PGRS38 inhibited the apoptosis of RAW264.7 cells by downregulating the expression of apoptotic markers including Bax, cytochrome c, caspase-3, and caspase-9. In a nutshell, our findings demonstrate that PE_PGRS38 is a virulence factor for Mtb that enables recombinant M. smegmatis to survive by resisting and evading the host’s immune responses during infection. Full article

The hair follicle is a specialized appendage of the skin that is critical for multiple functions, including thermoregulation, immune surveillance, and sebum production. Mammals are born with a fixed number of hair follicles that develop embryonically. Postnatally, these hair follicles undergo regenerative cycles of regression and growth that recapitulate many of the embryonic signaling pathways. Furthermore, hair cycles have a direct impact on skin regeneration in homeostasis, cutaneous wound healing, and disease conditions such as alopecia. Here, we review the current knowledge of hair follicle formation during embryonic development and the post-natal hair cycle, with an emphasis on the molecular signaling pathways underlying these processes. We then discuss efforts to capitalize on the field’s understanding of in vivo mechanisms to bioengineer hair follicles or hair-bearing skin in vitro and how such models may be further improved to develop strategies for hair regeneration. Full article

Previous reports have shown that various oral pulmonary vasodilators are effective against canine pulmonary hypertension (PH). However, no studies have compared their hemodynamic effects. We aimed to compare the hemodynamic effects of 15 µg/kg beraprost sodium, 1.0 mg/kg sildenafil, and their combination, in dogs with experimentally induced mitral regurgitation. This experimental crossover study evaluated the hemodynamic and functional effects of oral pulmonary vasodilators by application of right-sided heart catheterization and echocardiography. Beraprost significantly decreased pulmonary and systemic vascular resistance. Additionally, beraprost increased right-ventricular stroke volume and left-ventricular cardiac output without worsening left-heart size and left-atrial pressure. The pulmonary vasodilatory effects of sildenafil were stronger, and its systemic vasodilatory effects were weaker than those of beraprost. However, sildenafil significantly increased the left-ventricular volume, left-atrial pressure indicator, and right-ventricular cardiac output. Combination therapy resulted in the strongest pulmonary and systemic vasodilating effects without worsening the left-heart size and left-atrial pressure indicators. Both beraprost and sildenafil were effective against canine PH; however, sildenafil was associated with the risk of worsening left-heart loading. Combination therapy with beraprost and sildenafil synergistically dilated pulmonary and systemic vessels, indicating a more potent treatment option for severe PH cases. Full article

Coccolithophores play a significant role in marine calcium carbonate production and carbon cycles, attributing to their unique feature of producing calcareous plates, coccoliths. Coccolithophores also possess a haplo-diplontic life cycle, presenting distinct morphology types and calcification states. However, differences in nutrient acquisition strategies and mixotrophic behaviors of the two life phases remain unclear. In this study, we conducted a series of phagocytosis experiments of calcified diploid and non-calcified haploid strains of coccolithophore Gephyrocapsa huxleyi under light and dark conditions. The phagocytosis capability of each strain was examined based on characteristic fluorescent signals from ingested beads using flow cytometry and fluorescence microscopy. The results show a significantly higher phagocytosis percentage on fluorescent beads in the bacterial prey surrogates of the non-calcified haploid Gephyrocapsa huxleyi strain, than the calcified diploid strain with or without light. In addition, the non-calcified diploid cells seemingly to presented a much higher phagocytosis percentage in darkness than under light. The differential phagocytosis capacities between the calcified diploid and non-calcified haploid Gephyrocapsa huxleyi strains indicate potential distinct nutritional strategies at different coccolithophore life and calcifying stages, which may further shed light on the potential strategies that coccolithophore possesses in unfavorable environments such as twilight zones and the expanding coccolithophore niches in the natural marine environment under the climate change scenario. Full article

Where teleost fish are concerned, studies in tryptophan immunomodulation generally point to immunosuppressive properties, thus presenting a potential anti-inflammatory dietary strategy. The goal of the present work was to evaluate the effects of tryptophan dietary supplementation on immune and neuroendocrine responses of the European seabass, Dicentrarchus labrax, undergoing chronic inflammation. Juvenile European seabass were intraperitoneally injected with either Freund’s Incomplete Adjuvant (FIA, inflamed group) or a saline solution (control group). Within each group, fish were fed a control (CTRL) and a CTRL-based diet supplemented with tryptophan (0.3% DM basis; TRP) for 4 weeks. Different tissues were sampled every week for the assessment of immune-related parameters. When TRP was provided to FIA-injected fish, mcsfr gene expression increased from 1 to 2 weeks and remained high until the end of the experiment. The same fish showed a concurrent increase in peripheral monocyte counts. Moreover, il34 expression at 1 week post-FIA injection was higher in TRP-fed than in CTRL-fed fish. After one week, molecular patterns of anti-inflammatory processes seemed to be favoured by TRP (mcsfr, gr1, il34 and tgfβ). Altogether, the results show that the feeding period seems to be critical where tryptophan supplementation is concerned since at later inflammatory stages—and longer feeding periods—fish fed TRP displayed a molecular profile similar to that of the CTRL group. In contrast, shorter administration periods might accelerate immune regulatory pathways. Full article

The cloning of resistance-related genes CsROP5/CsROP10 and the analysis of their mechanism of action provide a theoretical basis for the development of molecular breeding of disease-resistant cucumbers. The structure domains of two Rho-related guanosine triphosphatases from plant (ROP) genes were systematically analyzed using the bioinformatics method in cucumber plants, and the genes CsROP5 (Cucsa.322750) and CsROP10 (Cucsa.197080) were cloned. The functions of the two genes were analyzed using reverse-transcription quantitative PCR (RT-qPCR), virus-induced gene silencing (VIGS), transient overexpression, cucumber genetic transformation, and histochemical staining technology. The conserved elements of the CsROP5/CsROP10 proteins include five sequence motifs (G1-G5), a recognition site for serine/threonine kinases, and a hypervariable region (HVR). The knockdown of CsROP10 through VIGS affected the transcript levels of ABA-signaling-pathway-related genes (CsPYL, CsPP2Cs, CsSnRK2s, and CsABI5), ROS-signaling-pathway-related genes (CsRBOHD and CsRBOHF), and defense-related genes (CsPR2 and CsPR3), thereby improving cucumber resistance to Corynespora cassiicola. Meanwhile, inhibiting the expression of CsROP5 regulated the expression levels of ROS-signaling-pathway-related genes (CsRBOHD and CsRBOHF) and defense-related genes (CsPR2 and CsPR3), thereby enhancing the resistance of cucumber to C. cassiicola. Overall, CsROP5 and CsROP10 may participate in cucumber resistance to C. cassiicola through the ROS and ABA signaling pathways. Full article

Cancer immune evasion represents a leading hallmark of cancer, posing a significant obstacle to the development of successful anticancer therapies. However, the landscape of cancer treatment has significantly evolved, transitioning into the era of immunotherapy from conventional methods such as surgical resection, radiotherapy, chemotherapy, and targeted drug therapy. Immunotherapy has emerged as a pivotal component in cancer treatment, harnessing the body’s immune system to combat cancer and offering improved prognostic outcomes for numerous patients. The remarkable success of immunotherapy has spurred significant efforts to enhance the clinical efficacy of existing agents and strategies. Several immunotherapeutic approaches have received approval for targeted cancer treatments, while others are currently in preclinical and clinical trials. This review explores recent progress in unraveling the mechanisms of cancer immune evasion and evaluates the clinical effectiveness of diverse immunotherapy strategies, including cancer vaccines, adoptive cell therapy, and antibody-based treatments. It encompasses both established treatments and those currently under investigation, providing a comprehensive overview of efforts to combat cancer through immunological approaches. Additionally, the article emphasizes the current developments, limitations, and challenges in cancer immunotherapy. Furthermore, by integrating analyses of cancer immunotherapy resistance mechanisms and exploring combination strategies and personalized approaches, it offers valuable insights crucial for the development of novel anticancer immunotherapeutic strategies. Full article

Cyanobacteria, photoautotrophic Gram-negative bacteria, play a crucial role in aquatic and terrestrial environments, contributing significantly to fundamental ecological processes and displaying potential for various biotechnological applications. It is, therefore, critical to identify viable strains for aquaculture and establish accurate culture parameters to ensure an extensive biomass supply for biotechnology purposes. This study aims to establish optimal laboratory batch culture conditions for Nostoc 136, sourced from Alga₂O, Coimbra, Portugal. Preliminary investigations were conducted to identify the optimal culture parameters and to perform biomass analysis, including protein and pigment content. The highest growth was achieved with an initial inoculum concentration of 1 g.L⁻¹, using modified BG11 supplemented with nitrogen, resulting in a Specific Growth Rate (SGR) of 0.232 ± 0.017 μ.day⁻¹. When exposed to white, red, and blue LED light, the most favourable growth occurred under a combination of white and red LED light exhibiting an SGR of 0.142 ± 0.020 μ.day⁻¹. The protein content was determined to be 10.80 ± 2.09%. Regarding the pigments, phycocyanin reached a concentration of 200.29 ± 30.07 µg.mL⁻¹, phycoerythrin 148.29 ± 26.74 µg.mL⁻¹, and allophycocyanin 10.69 ± 6.07 µg.mL⁻¹. This study underscores the influence of light and nutrient supplementation on the growth of the Nostoc biomass. Full article

The assassin bug Sycanus bifidus has a wide distribution across southern China. This study explored its distribution and evolution by analyzing mitochondrial and nuclear ribosomal RNA genes, revealing how Pleistocene climate and geological changes shaped its phylogeography. We identified two main clades, A and B, that diverged in the Middle Pleistocene. Hainan Island’s populations form a unique group within Clade A, suggesting that the Qiongzhou Strait served as a dispersal corridor during glaciation. Rising sea levels likely separated the Hainan population afterward. Ecological niche modeling showed that both populations have been viable since the last interglacial period, with demographic analyses indicating possible expansions during the Middle and Late Pleistocene, driven by favorable climates. This study highlights the significant effects of Pleistocene sea-level and climatic changes on the distribution and evolution of S. bifidus in China. Full article

Thyroid Cancer (TC) is the most common endocrine malignancy, with increasing incidence globally. Papillary thyroid cancer (PTC), a differentiated form of TC, accounts for approximately 90% of TC and occurs predominantly in women of childbearing age. Although responsive to current treatments, recurrence of PTC by middle age is common and is much more refractive to treatment. Undifferentiated TC, particularly anaplastic thyroid cancer (ATC), is the most aggressive TC subtype, characterized by it being resistant and unresponsive to all therapeutic and surgical interventions. Further, ATC is one of the most aggressive and lethal malignancies across all cancer types. Despite the differences in therapeutic needs in differentiated vs. undifferentiated TC subtypes, there is a critical unmet need for the identification of molecular biomarkers that can aid in early diagnosis, prognosis, and actionable therapeutic targets for intervention. Advances in the field of cancer genomics have enabled for the elucidation of differential gene expression patterns between tumors and healthy tissue. A novel category of molecules, known as non-coding RNAs, can themselves be differentially expressed, and extensively contribute to the up- and downregulation of protein coding genes, serving as master orchestrators of regulated and dysregulated gene expression patterns. These non-coding RNAs have been identified for their roles in driving carcinogenic patterns at various stages of tumor development and have become attractive targets for study. The identification of specific genes that are differentially expressed can give insight into mechanisms that drive carcinogenic patterns, filling the gaps of deciphering molecular and cellular processes that modulate TC subtypes, outside of well-known driver mutations. Full article

Stress is an important risk factor for the onset of anxiety and depression. The ability to cope with stressful events varies among different subjects, probably depending on different genetic variants, sex and previous life experiences. The Val66Met variant of Brain-Derived Neurotrophic Factor (BDNF), which impairs the activity-dependent secretion of BDNF, has been associated with increased susceptibility to the development of various neuropsychiatric disorders. Adult male and female wild-type Val/Val (BDNF^V/V) and heterozygous Val/Met (BDNF^V/M) mice were exposed to two sessions of forced swimming stress (FSS) per day for two consecutive days. The mice were behaviorally tested 1 day (short-term effect) or 11 days (long-term effect) after the last stress session. Protein and mRNA levels were measured in the hippocampus 16 days after the end of stress exposure. Stressed mice showed a higher anxiety-like phenotype compared to non-stressed mice, regardless of the sex and genotype, when analyzed following the short period of stress. In the prolonged period, anxiety-like behavior persisted only in male BDNF^V/M mice (p < 0.0001). Interestingly, recovery in male BDNF^V/V mice was accompanied by an increase in pCREB (p < 0.001) and Bdnf4 (p < 0.01) transcript and a decrease in HDAC1 (p < 0.05) and Dnmt3a (p = 0.01) in the hippocampus. Overall, our results show that male and female BDNF Val66Met knock-in mice can recover from subchronic stress in different ways. Full article

Metformin, a widely used anti-diabetic drug, has garnered attention for its potential in cancer management, particularly in breast and colorectal cancer. It is established that metformin reduces mitochondrial respiration, but its specific molecular targets within mitochondria vary. Proposed mechanisms include inhibiting mitochondrial respiratory chain Complex I and/or Complex IV, and mitochondrial glycerophosphate dehydrogenase, among others. These actions lead to cellular energy deficits, redox state changes, and several molecular changes that reduce hyperglycemia in type 2 diabetic patients. Clinical evidence supports metformin’s role in cancer prevention in type 2 diabetes mellitus patients. Moreover, in these patients with breast and colorectal cancer, metformin consumption leads to an improvement in survival outcomes and prognosis. The synergistic effects of metformin with chemotherapy and immunotherapy highlights its potential as an adjunctive therapy for breast and colorectal cancer. However, nuanced findings underscore the need for further research and stratification by molecular subtype, particularly for breast cancer. This comprehensive review integrates metformin-related findings from epidemiological, clinical, and preclinical studies in breast and colorectal cancer. Here, we discuss current research addressed to define metformin’s bioavailability and efficacy, exploring novel metformin-based compounds and drug delivery systems, including derivatives targeting mitochondria, combination therapies, and novel nanoformulations, showing enhanced anticancer effects. Full article

Neurological commitment is a neglected manifestation of Chagas disease (CD). Meningoencephalitis mainly affects children and immunosuppressed patients, while stroke can occur with or without cardiac compromise. One of the possible causes of stroke development is microvascular commitment. Our group previously described that experimental Trypanossoma cruzi acute infection leads to cerebral microvasculopathy. This condition is characterized by decreased capillary density, increased leukocyte rolling and adhesion, and endothelial dysfunction. CD was discovered 114 years ago, and until today, only two drugs have been available for clinical treatment: benznidazole and nifurtimox. Both present a high cure rate for the acute phase (80%) and small cure rate for the chronic phase (20%). In addition, the high occurrence of side-effects, without proper medical follow-up, can result in treatment abandonment. Therefore, the search for new therapeutic schemes is necessary. Statins are drugs already used in the clinic that have several pleiotropic effects including endothelial function improvement, anti-inflammatory action, as well as trypanocidal effects, making them a potential alternative treatment for brain microvasculopathy in CD. Here, we investigate the effect of lovastatin (LOV) on brain microvasculopathy and inflammatory parameters. Swiss Webster mice were intraperitoneally inoculated with the Y strain of T. cruzi. Treatment with lovastatin (20 mg/kg/day) was initiated 24 h after the infection and continued for 14 consecutive days. We observed that LOV treatment did not affect parasitemia, brain microcirculation alterations, or the reduction in cerebral blood flow caused by T. cruzi infection. Also, LOV did not prevent the increased number of CD3+ cells and eNOS levels in the T. cruzi-infected brain. No alterations were observed on VCAM-1 and MCP-1 expressions, neither caused by infection nor LOV treatment. However, LOV prevented the increase in F4/80+ cells and ICAM-1 levels in the brain caused by acute infection with T. cruzi. These results suggest an anti-inflammatory activity of LOV, but more studies are needed to elucidate the role of LOV in CD acute infection. Full article

Vibrio parahaemolyticus is one of the main causative agents leading to acute hepatopancreatic necrosis disease, the severe bacterial disease that occurs during shrimp aquaculture. Hemocytes play important roles during Vibrio infection. Previously, we found that there were few differentially expressed genes (DEGs) between hemocytes from V. parahaemolyticus-resistant and -susceptible shrimp before infection. We considered that there should be different immune responses between them after a pathogen infection. Here, the transcriptome data of hemocytes from V. parahaemolyticus-resistant and -susceptible shrimp before and after a pathogen infection were compared. The results showed that there were 157 DEGs responsive to infection in V. parahaemolyticus-resistant shrimp, while 33 DEGs in V. parahaemolyticus-susceptible shrimp. DEGs in V. parahaemolyticus-resistant shrimp were mainly related to immune and glycolytic processes, while those in V. parahaemolyticus-susceptible shrimp were mainly related to metabolism, with only two DEGs in common. A further analysis of genes involved in glucose metabolism revealed that GLUT2, HK, FBP, and PCK1 were lowly expressed while PC were highly expressed in hemocytes of the V. parahaemolyticus-resistant shrimp, indicating that glucose metabolism in shrimp hemocytes was related to a V. parahaemolyticus infection. After the knockdown of PC, the expression of genes in Toll and IMD signaling pathways were down-regulated, indicating that glucose metabolism might function through regulating host immunity during V. parahaemolyticus infection. The results suggest that the immune responses between V. parahaemolyticus-resistant and -susceptible shrimp were apparently different, which probably contribute to their different V. parahaemolyticus resistance abilities. Full article

Though different types of commercial probiotics are supplemented in biofloc technology (BFT), very little information is available on their effects on the farmed fish. Therefore, this study focused on evaluating the effects of three most commonly used commercial probiotics on the growth performance, intestinal histomorphology, and intestinal microbiota of Nile tilapia (Oreochromis niloticus) reared in BFT. Tilapia fry, with an average weight of 3.02 ± 0.50 g, were stocked at a density of 60 fry/0.2 m³, and cultured for 90 days. Three commercial probiotics were administered, with three replications for each: a single-genus multi-species probiotic (Bacillus spp.) (T1), a multi-genus multi-species probiotic (Bacillus sp., Lactobacillus sp., Nitrosomonas sp., Nitrobacter sp.) (T2), and a multi-species probiotic (Bacillus spp.) combined with enzymes including amylase, protease, cellulase, and xylanase (T3). The results showed significant variations in growth and feed utilization, with T3 outperforming other treatments in terms of weight gain, liver weight, and intestine weight. Adding Bacillus spp. with enzymes (T3) to water significantly increased the histomorphological parameters (villi length, villi depth, crypt depth, muscle thickness, intestinal thickness) as well as microbes (total viable count and total lactic acid bacteria) of intestine of fish compared to T1 and T2, leading to improved digestion and absorption responses. It is concluded that the supplementation of commercial probiotics has potential benefits on farmed fish species in BFT. Full article

Connexins (Cxs) are a family of integral membrane proteins, which function as both hexameric hemichannels (HCs) and dodecameric gap junction channels (GJCs), behaving as conduits for the electrical and molecular communication between cells and between cells and the extracellular environment, respectively. Their proper functioning is crucial for many processes, including development, physiology, and response to disease and trauma. Abnormal GJC and HC communication can lead to numerous pathological states including inflammation, skin diseases, deafness, nervous system disorders, and cardiac arrhythmias. Over the last 15 years, high-resolution X-ray and electron cryomicroscopy (cryoEM) structures for seven Cx isoforms have revealed conservation in the four-helix transmembrane (TM) bundle of each subunit; an αβ fold in the disulfide-bonded extracellular loops and inter-subunit hydrogen bonding across the extracellular gap that mediates end-to-end docking to form a tight seal between hexamers in the GJC. Tissue injury is associated with cellular Ca²⁺ overload. Surprisingly, the binding of 12 Ca²⁺ ions in the Cx26 GJC results in a novel electrostatic gating mechanism that blocks cation permeation. In contrast, acidic pH during tissue injury elicits association of the N-terminal (NT) domains that sterically blocks the pore in a “ball-and-chain” fashion. The NT domains under physiologic conditions display multiple conformational states, stabilized by protein–protein and protein–lipid interactions, which may relate to gating mechanisms. The cryoEM maps also revealed putative lipid densities within the pore, intercalated among transmembrane α-helices and between protomers, the functions of which are unknown. For the future, time-resolved cryoEM of isolated Cx channels as well as cryotomography of GJCs and HCs in cells and tissues will yield a deeper insight into the mechanisms for channel regulation. The cytoplasmic loop (CL) and C-terminal (CT) domains are divergent in sequence and length, are likely involved in channel regulation, but are not visualized in the high-resolution X-ray and cryoEM maps presumably due to conformational flexibility. We expect that the integrated use of synergistic physicochemical, spectroscopic, biophysical, and computational methods will reveal conformational dynamics relevant to functional states. We anticipate that such a wealth of results under different pathologic conditions will accelerate drug discovery related to Cx channel modulation. Full article

Crassostrea hongkongensis is an economically important bivalve found in various parts of the South China Sea. A new interspecific backcross ([(Crassostrea hongkongensis ♀ × C. gigas ♂) ♂ × C. hongkongensis ♀]) variety was bred by the South China Sea Institute of Oceanology which named “South China No. 1”. This study aims to explore the effects of stocking density on the growth performance of “South China No. 1”, compared their growth performance and genetic diversity to C. hongkongensis, and found the best place breeding site for “South China No. 1” in Beibu Gulf. The results showed that stocking a density of 20 oysters/substrate can significantly increase the shell height, shell width, total weight, survival rate, daily shell height gain and daily body mass gain. It was found that the shell height and total weight of “South China No. 1” cultured in Fangchenggang were significantly higher than that of those in Beihai and Qinzhou from September 2018 to November 2018. Similarly, the shell width of oysters in Fangchenggang and Qinzhou was also significantly higher in September 2018, and the interaction between site and stocking density had significant effects on the shell width in March 2018 and November 2018. In addition, the shell height and shell width of “South China No. 1” were significantly higher than that of C. hongkongensis in all three sites. At all three sites, the phytoplankton community structure was mostly dominated by Bacillariophyta. In the Hardy–Weinberg equilibrium test, for the seven populations and ten microsatellites, in 10 of the 70 groups, the segregation distortion was significant. These results suggest that a stocking density of 20 oysters/substrate can promote the shell height, shell width and total weight of “South China No. 1” in Beibu Gulf, China. “South China No. 1” has better growth performance compared with C. hongkongensis. Fangchenggang is a suitable place to cultivate the “South China No. 1” breed according to the total weight and sum of all algal genus abundances. The results of this study can be used as a reference to further understand the stocking density and genetic diversity of the “South China No. 1” breed in Beibu Gulf, China. Full article

Background: Dysbiosis, influenced by poor diet or stress, is associated with various systemic diseases. Probiotic supplements are recognized for stabilizing gut microbiota and alleviating gastrointestinal issues, like irritable bowel syndrome (IBS). This study focused on the tryptophan pathways, which are important for the regulation of serotonin levels, and on host physiology and behavior regulation. Methods: Nanovesicles were isolated from the plasma of subjects with chronic diarrhea, both before and after 60 days of consuming a probiotic mix (Acronelle^®, Bromatech S.r.l., Milan, Italy). These nanovesicles were assessed for the presence of Tryptophan 2,3-dioxygenase 2 (TDO 2). Furthermore, the probiotics mix, in combination with H₂O₂, was used to treat HT29 cells to explore its cytoprotective and anti-stress effect. Results: In vivo, levels of TDO 2 in nanovesicles were enhanced in the blood after probiotic treatment, suggesting a role in the gut–brain axis. In the in vitro model, a typical H₂O₂-induced stress effect occurred, which the probiotics mix was able to recover, showing a cytoprotective effect. The probiotics mix treatment significantly reduced the heat shock protein 60 kDa levels and was able to preserve intestinal integrity and barrier function by restoring the expression and redistribution of tight junction proteins. Moreover, the probiotics mix increased the expression of TDO 2 and serotonin receptors. Conclusions: This study provides evidence for the gut–brain axis mediation by nanovesicles, influencing central nervous system function. Full article

The aim of this study was to investigate the effect of a series of 20 whole-body cryotherapy sessions and 20 winter swimming sessions on the level of catalase, glutathione peroxidase and superoxide dismutase. The experimental group consisted of 60 people (30 people received cryotherapy and 30 people swam in cold water). The control group—without intervention: 30 people. Each of the three groups was tested twice. Analyzing the changes in the examined indicators, a statistical increase of CAT was observed in men after the use of WBC, as well as an increase of SOD in women and a decrease of SOD in men after the winter swimming season. Regular WS does not seem to place an excessive burden on the body in terms of intensifying oxidative processes. WS sessions once a week can be recommended as an effective method of improving health by causing positive adaptive changes and strengthening the body’s antioxidant barrier. WBC may be used as an adjunct therapy in the treatment of diseases caused by oxidative stress, as it improves the body’s antioxidant capacity. Further research is needed to elucidate antioxidant mechanisms in humans and to determine the short- and long-term effects of exposure to WS and WBC. Full article

The use of organic compounds in different spheres of human activity is accompanied by their influx to and accumulation in the environment. The negative impact of those compounds can be one of the reasons for a decline in populations and biodiversity of aboveground invertebrates. Chemical compounds can potentially cause a variety of effects (attractant or repellent) on insects, including species of the Staphylinidae family. In a laboratory experiment, we identified repellent and attractant influence of 40 organic compounds and mixtures of compounds (acids, alcohols, ketones, phenols, aldehydes, aromatic carbohydrates solvents, and vehicle fuels) on Philonthus decorus Gravenhorst, 1802. The ambulatory responses of the males and females to the same chemical compounds most often varied. A strong repellent activity against both sexes of Ph. decorus was caused by oleic acid, while hexane repelled the males. Acetic acid, 1-butanol, and ammonia solution were found to be strongly repellent against females. A moderate (average) repellent activity towards male Ph. decorus was displayed by organic solvents and fuels, some alcohols (isopropanol, isoamyl alcohol, methanol, ethanol), acids (acetic, formic acid), aromatic carbohydrates (toluene, xylene), and formaldehyde. Female Ph. decorus in general were less sensitive to the odors. The list of repellents with moderate activity against the females was much shorter: solvent 646, white spirit, toluene, isopropanol, isoamyl alcohol, citric and oxalic acids, and glycerol. Moderate attractant activity for Ph. decorus was exhibited by some amino acids, alcohols, and fuel mixes: glycine and L-cysteine (for the males), and phenylalanine, methanol, and diesel fuel (for the females). The rest of the 40 chemical compounds we studied caused no ambulatory responses in Ph. decorus. The difficulties we encountered in the interpretation of the results suggest a need for further experimental studies that would expand the knowledge of the chemoecology of insects. Full article

Microplastics and nanoplastics are abundant in the environment. Further research is necessary to examine the consequences of microplastic contamination on living species, given its widespread presence. In our research, we determined the toxic effects of PET microplastics on Drosophila melanogaster at the cellular and genetic levels. Our study revealed severe cytotoxicity in the midgut of larvae and the induction of oxidative stress after 24 and 48 h of treatment, as indicated by the total protein, Cu-Zn SOD, CAT, and MDA contents. For the first time, cell damage in the reproductive parts of the ovaries of female flies, as well as in the accessory glands and testes of male flies, has been observed. Furthermore, a decline in reproductive health was noted, resulting in decreased fertility among the flies. By analyzing stress-related genes such as hsp83, hsp70, hsp60, and hsp26, we detected elevated expression of hsp83 and hsp70. Our study identified hsp83 as a specific biomarker for detecting early redox changes in cells caused by PET microplastics in all the treated groups, helping to elucidate the primary defense mechanism against PET microplastic toxicity. This study offers foundational insights into the emerging environmental threats posed by microplastics, revealing discernible alterations at the genetic level. Full article

Securing food, energy, and raw materials for a growing population is one of the most significant challenges of our century. Algae play a central role as an alternative to plants. Wastewater and flue gas can secure nutrients and CO₂ for carbon fixation. Unfortunately, algae domestication is necessary to enhance biomass production and reduce cultivation costs. Nannochloropsis spp. have increased in popularity among microalgae due to their ability to accumulate high amounts of lipids, including PUFAs. Recently, the interest in the use of Nannochloropsis spp. as a green bio-factory for producing high-value products increased proportionally to the advances of synthetic biology and genetic tools in these species. In this review, we summarized the state of the art of current nuclear genetic manipulation techniques and a few examples of their application. The industrial use of Nannochloropsis spp. has not been feasible yet, but genetic tools can finally lead to exploiting this full-of-potential microalga. Full article

The last few decades have brought contraception to the forefront of research, with great strides made in effectively targeting and optimizing the physiology, pharmacology, and delivery processes that prevent pregnancy. However, these advances still predominantly target female contraceptives for the prevention of contraception, whereas targeting the male sex has lagged far behind. This has led to a marked deficiency in safe and effective male contraceptive agents, resulting in a heavy dependence on female contraceptives to prevent unwanted and unplanned pregnancies. Current research in the veterinary field and in rodents highlights several promising avenues whereby novel, safe, and effective male contraceptive alternatives are being developed—with an emphasis on reduced side effects and reversibility potential. This review aims to discuss current and novel male contraceptives (both human and veterinary formulations) while highlighting their efficacy, advantages, and disadvantages. Full article

The evolution of facial muscles in dogs has been linked to human preferential selection of dogs whose faces appear to communicate information and emotion. Dogs who convey, especially with their eyes, a sense of perceived helplessness can elicit a caregiving response from humans. However, the facial muscles used to generate such expressions may not be uniquely present in all dogs, but rather specifically cultivated among various taxa and individuals. In a preliminary, qualitative gross anatomical evaluation of 10 canid specimens of various species, we find that the presence of two facial muscles previously implicated in human-directed canine communication, the levator anguli occuli medialis (LAOM) and the retractor anguli occuli lateralis (RAOL), was not unique to domesticated dogs (Canis familiaris). Our results suggest that these aspects of facial musculature do not necessarily reflect selection via human domestication and breeding. In addition to quantitatively evaluating more and other members of the Canidae family, future directions should include analyses of the impact of superficial facial features on canine communication and interspecies communication between dogs and humans. Full article