Search Results (7,823)

Traditional diets based on diverse edible plants are increasingly threatened by climate change, which exposes crops to abiotic and biotic stressors such as drought, soil salinity, UV radiation, microorganisms, and insect herbivory. Understanding how these conditions influence both the nutritional and nutraceutical profiles, as well as the availability of key compounds, is essential to preserve their functional value. Piper auritum Kunth, used in Mexican gastronomy, was selected to assess two abiotic stress scenarios: drought stress (DS) and salicylic acid (SA) to simulate plant defense against pathogens and/or predators. We evaluated proximate composition, dietary fiber, total phenolics, total flavonoids, antioxidant capacity, low molecular weight carbohydrates (LMWCs), monomeric composition, and essential oil volatiles. Additionally, the simulated gastrointestinal digestion (INFOGEST) with an additional rat small-intestine extract (RSIE) revealed that both SA and DS shifted sugar distribution, especially for soluble and structural pools. SA treatment correlated with synthesis of secondary metabolites, particularly oxygenated and hydrocarbon terpenes. Both abiotic stressors modulated LMWC release during digestion, altering the distribution of sugars such as raffinose and galacturonic acid, with potential prebiotic implications. Essential oil analysis revealed stress-specific shifts in volatile composition, particularly in safrole, β-caryophyllene, and related terpenes. Beyond individual compound changes, the combined evaluation of composition, antioxidant properties, and volatile profile provides a comprehensive view of how abiotic stress can reshape the functional potential of P. auritum. To our knowledge, this is the first report on LMWC relative abundance across INFOGEST stages for a quelite species and on the integrated effect of DS and SA on its chemical profile. These findings highlight the importance of including compound release and functional traits, alongside chemical characterization, in future assessments of traditional plants under climate-related stress to safeguard their contribution to sustainable diets. Full article

Filoviruses are among the most lethal viral human pathogens known, with significant relevance to public health, yet their evolutionary history remains poorly resolved. This study applied a multiprotein molecular phylogenetic approach to investigate the evolutionary and temporal dynamics of the family Filoviridae. Amino acid sequences from the proteome and seven individual proteins (NP, VP35, VP40, GP, VP30, VP24, L) were analyzed using MEGA 12, with RelTime inference anchored on uniform calibrations, and integration of epidemiological data (cases, fatalities, case fatality). The phylogenetic reconstructions revealed robust topologies for most proteins, though selective pressures on GP, VP30 and VP40 generated more variable patterns. Temporal inferences supported the classification of filoviruses into three groups: an ancestral lineage (>1 MYA, fish- and reptile-associated), an intermediate lineage (BCE–1 MYA, bat-associated), and a contemporary lineage (CE, ebolaviruses and marburgviruses). VP30 and VP40 showed consistent associations with epidemiological outcomes in Orthoebolavirus zairense, suggesting their interplay may underlie enhanced dispersal and virulence. Contrariwise, Orthoebolavirus restonense emerged as a natural counterpoint for comparison with other potential human pathogenic filoviruses. Taken together, these findings highlight that filoviral evolution is intrinsically linked not only to viral biology but also to the ecology and history of their hosts. Full article

Although bovine respiratory syncytial virus (BRSV) is a key contributor to bovine respiratory disease (BRD) worldwide, there are few detailed reports of BRSV-related outbreaks in Brazil. This study describes the clinical, pathological, immunohistochemical (IHC), and molecular findings from a BRD outbreak in adult dairy cows from Southern Brazil. The affected cattle had dyspnea, nasal discharge, and coughing. One cow died, and samples were collected for diagnosis. Histopathology revealed interstitial pneumonia with multinucleated giant cells. IHC identified BRSV antigens in pulmonary tissue. A multiplex real-time PCR identified BRSV, Histophilus somni, and Pasteurella multocida in nasal and oral swabs, while only BRSV and H. somni were detected in the tissues of the cow that died. All animals had co-infections involving BRSV. The average cycle threshold (Cq) values for BRSV were 27.43 (nasal) and 32.68 (oral), with significant differences (p = 0.016), indicating higher nasal shedding. This qPCR assay was effective for detecting BRD pathogens, the quantification of viral and bacterial loads in animals with BRD and can be used for the rapid detection of respiratory pathogens. The elevated BRSV detection in oral samples suggests that this route may be an alternative for the collection of samples in cattle with profuse nasal discharge. Full article

Cyclic di-GMP (c-di-GMP), a universal second messenger in bacteria, orchestrates a wide array of essential life processes. Its intracellular dynamics are meticulously regulated by diguanylate cyclases (DGCs) and phosphodiesterases (PDEs), ensuring precise spatiotemporal control. The functional output of c-di-GMP signaling hinges on effector proteins—molecular decoders that translate c-di-GMP signals into specific cellular responses. This review systematically examines diverse classes of c-di-GMP effectors, using several representative bacterial species as model systems, to dissect their structural and mechanistic diversity. Particular emphasis is placed on their pivotal roles in bacterial pathogenicity, antibiotic tolerance, and host–pathogen interactions, offering fresh insights into the regulatory mechanisms underlying c-di-GMP signaling. Full article

Enteroviruses (EVs), particularly those within the species Enterovirus A and B, represent a significant global public health burden, especially in infants and young children. While often causing self-limiting hand, foot, and mouth disease (HFMD), certain serotypes can lead to severe neurological and cardiopulmonary complications. This comprehensive review focuses on the major pathogenic serotypes, including enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), coxsackievirus A6 (CV-A6), coxsackievirus B3 (CV-B3), and enterovirus D68 (EV-D68). We began by reconstructing a phylogenetic tree based on VP1 protein sequences, elucidating the genetic relationships and evolutionary patterns among these serotypes, which underpin their diverse antigenicity and epidemiology. Building upon this genetic foundation, the review then provides a detailed synthesis of their distinct pathogenesis, highlighting the five-phase clinical progression from exanthematous phase to convalescence, and their unique tropisms for target organs such as the central nervous system and heart. Progressing to the molecular mechanisms, a critical component of this work is a systematic summary of the specific host receptors that mediate viral entry, including SCARB2 for EV-A71 and CV-A16, sialic acid and ICAM-5 for EV-D68, and CAR/CD55 for CV-B3, explaining the mechanistic basis for their tissue specificity and pathogenicity. Finally, to translate these insights into clinical applications, we critically evaluate the current landscape of vaccine development, noting the high efficacy (~90%) of inactivated EV-A71 vaccines in Asia and the significant global success of poliovirus vaccines, while also addressing the stark lack of cross-protective or licensed vaccines for other prevalent serotypes like CV-A16, CV-A6, and EV-D68. The review concludes that the high genetic diversity and serotype-specific immunity of enteroviruses pose a major challenge, necessitating a concerted shift towards the development of broad-spectrum vaccines and therapeutics informed by an integrated understanding of viral evolution, receptor usage, and pathogenesis. Full article

Wheat blast, caused by Magnaporthe oryzae pathotype Triticum (MoT), poses a major threat to wheat (Triticum aestivum) cultivation, particularly in South America and Bangladesh. The rapid evolution and spread of the pathogen necessitate the development of durable and broad-spectrum resistance in wheat cultivars. This review summarizes current insights into the multi-layered defense mechanisms of wheat, encompassing resistance (R) genes, pattern-triggered immunity (PTI), and effector-triggered immunity (ETI) against MoT. The R-genes provide race-specific resistance through ETI, while both ETI and PTI are required to form integral layers of the plant immune system that synergistically reinforce host defense network. Recent advances in genomics, transcriptomics, and molecular breeding have facilitated the discovery and deployment of key R-genes and signaling components involved in PTI and ETI pathways. Integrating these immune strategies through gene pyramiding, marker-assisted selection (MAS), and genome editing offers a promising route towards enhanced and durable resistance in hosts. Harnessing and optimizing these multilayered immune systems will be pivotal to securing wheat productivity amid the growing threat of wheat blast. Full article

Background/Objectives: The growing threat of antimicrobial resistance has intensified the search for alternative therapeutic approaches. Quorum sensing (QS) inhibition, which disrupts bacterial communication and virulence, represents a promising approach to mitigating infection. Given the complexity of the sponge holobiont, sponge-associated microorganisms may demonstrate QS inhibitory properties and serve as potential sources of novel anti-virulence agents. This study aimed to investigate the QS inhibitory potential of sponge-associated Bacillus species against Pseudomonas aeruginosa, a multidrug-resistant pathogen that relies on QS for virulence regulation. Methods: Ninety-eight bacterial isolates were obtained from seven intertidal South African sponges. Biosensor-based sandwich assays using Chromobacterium violaceum identified 15 isolates with putative QS inhibition (QSI) activity, including five classified as Bacillus species via 16S rRNA gene sequencing. Crude extracts from these isolates, cultivated in medium Mannitol (Mann) and medium 5294, were screened for their ability to inhibit QS-regulated virulence factors in P. aeruginosa. Results: Extracts, particularly from medium 5294, exhibited significant QSI activity without cytotoxic effects. The five most potent extracts, i.e., Bacillus mobilis SP2-AB7 (5294), Bacillus wiedmannii SP5-AB7 (Mann), B. mobilis SP2-AB7 (Mann), and Bacillus cereus SP1-AB4 (Mann and 5294), inhibited both Las- and Rhl-regulated virulence factors, including pyocyanin, pyoverdine, elastase, protease, rhamnolipid production, motility, and initial adhesion, achieving inhibition rates of up to 93% (p < 0.05). Molecular analysis confirmed the presence of the aiiA lactonase gene in key isolates, while GC-MS and FTIR profiling revealed medium-specific differences in metabolite production. Conclusions: Sponge-associated Bacillus species from KwaZulu-Natal exhibit robust QSI activity against P. aeruginosa, highlighting their potential as sources of alternative anti-virulence agents. Further characterization and in vivo validation are needed to assess their therapeutic application in combatting resistant infections. Full article

Background/Objectives: Lower-grade gliomas, particularly IDH-mutant astrocytomas, represent a distinct molecular subtype with unique therapeutic challenges. Whole-genome sequencing (WGS) plays a crucial role in uncovering genetic alterations that drive glioma pathogenesis and therapeutic resistance. This study identifies and evaluates a novel GATA2 p.Arg396Trp mutation in a clinical sample of lower-grade glioma, assessing its structural impact and implications for drug binding. Methods: A WHO Grade II astrocytoma specimen from a 33-year-old female patient was analyzed using WGS with Oxford Nanopore sequencing, followed by comprehensive bioinformatics processing to identify genomic variants. The GATA2 p.Arg396Trp mutation was evaluated using protein modeling, structural analysis, and pathogenicity prediction tools. Drug affinity analysis was conducted using molecular docking simulations to assess the computational impact of the mutation on drug binding. Results: The GATA2 p.Arg396Trp mutation was identified as a computationally predicted pathogenic variant, potentially disrupting protein interactions within critical functional domains. Structural analysis revealed altered binding dynamics with key anti-neoplastic agents, suggesting potential implications for therapeutic response. These findings represent computational predictions requiring experimental validation. Conclusions: Our preliminary findings suggest a potential role of the GATA2 p.Arg396Trp mutation in lower-grade glioma pathogenesis. The mutation predicted impact on transcriptional regulation and drug affinity suggests GATA2 as a possible biomarker candidate. Extensive experimental validation in larger patient cohorts is needed to establish clinical relevance and explore targeted therapeutic strategies. Full article

Periodontitis is a globally prevalent oral disease and is closely associated with various systemic diseases. Periodontitis arises from dynamic and complex interactions between polymicrobial communities and host immune responses. Extracellular vesicles (EVs) are circulating subcellular particles carrying multiple signaling molecules. EVs play a key role in intercellular communication, and hold promise for diagnostic and therapeutic purposes. Bacterial extracellular vesicles (BEVs), released from oral pathogens, have been implicated in delivering virulence factors to host cells. In contrast, host cell-derived EVs (CEVs), secreted by periodontal cells, contain molecular cargo that reflect disease status. Both BEVs and CEVs contribute to periodontitis progression by exacerbating inflammation and tissue destruction, and they may also influence related systemic diseases. Moreover, the molecular components of EVs derived from saliva and gingival crevicular fluid (GCF) show potential as diagnostic biomarkers for periodontitis. In addition, mesenchymal stem cell-derived EVs (MSC-EVs) exhibit therapeutic potential in periodontitis, and engineering approaches have been developed to enhance their therapeutic efficacy and accelerate clinical translation. This review summarizes recent advances in understanding the pathogenic, diagnostic, and therapeutic roles of EVs in periodontitis and discusses current challenges and future directions toward their clinical application. Full article

Background: Enterotoxigenic Escherichia coli (ETEC) is a zoonotic pathogen causing diarrhea and mortality in infants and livestock. Its numerous serotypes necessitate the urgent development of multivalent vaccines for effective prevention, thereby reducing public health and economic threats. Methods: Computational bioinformatics analyses were conducted on five major ETEC adhesins structural subunits (FaeG, FanC, FasA, FimF41a, and FedF). Dominant epitopes were selected and concatenated via flexible linkers, incorporating the PADRE sequence and LTb adjuvant to design a multi-epitope fusion antigen (MEFA). The recombinant MEFA protein was expressed in a prokaryotic system. Furthermore, molecular dynamics simulations, docking, and immune simulations assessed structural stability and immunogenicity. Immunoreactivity was tested by Western blot. Murine immunization evaluated antibody responses, lymphocyte proliferation, cytokine secretion, and protection against ETEC challenge. Results: Structural modeling showed an extended conformation, with docking and simulations indicating strong immune activation. Western blot confirmed MEFA immunoreactivity. MEFA induced high antigen-specific antibody titers, enhanced splenocyte proliferation, and increased IFN-γ and IL-4 secretion, indicating a Th2-biased response in mice. Vaccinated mice survived lethal ETEC challenge and maintained intestinal integrity. Conclusions: The MEFA candidate vaccine effectively induces robust humoral and cellular immune responses and provides protection against ETEC infection, representing a promising strategy for next-generation multivalent ETEC vaccines. Full article

Chronickidney disease (CKD) poses a major global public health challenge, driven by a complex pathogenesis involving multiple interconnected processes—including metabolic disturbances, chronic inflammation, oxidative stress, endoplasmic reticulum stress, and ferroptosis—which collectively contribute to progressive and often irreversible loss of renal function. Although current standard therapies can ameliorate CKD progression, a substantial number of patients still advance to end-stage renal disease, highlighting the urgent need for innovative treatment strategies. Natural products have shown great promise in the prevention and management of CKD, largely attributable to their multi-target and multi-pathway synergistic effects. This review systematically outlines the core pathogenic mechanisms underlying CKD and elucidates the molecular mechanisms through which bioactive natural compounds exert renoprotective effects. Despite robust preclinical evidence, the clinical translation of these compounds remains hindered by limitations such as poor bioavailability and a lack of large-scale clinical trials. Moving forward, research should prioritize clinical translation of these compounds, aiming to provide novel therapeutic perspectives for CKD management. Full article

Bovine tuberculosis (bTB) is mainly caused by Mycobacterium bovis, which affects cattle, leading to significant economic losses. In Chile, the vaccination with the M. bovis Bacillus Calmette-Guérin (BCG) strain has been implemented in dairy herds with high prevalence of bTB. This study evaluated non-specific protection associated with BCG on the detection of pathogen-associated genes (nsp5, stx1, stx2, invA, IS1081) and mortality related to diarrhea and pneumonia in calves. A total of 186 calves from a commercial dairy farm were enrolled and grouped as vaccinated (n = 96) and non-vaccinated (n = 90). The BCG Russia strain (2–5 × 10⁵ UFC) was inoculated subcutaneously within the first 30 days after birth. Animals were monitored through fecal sampling at 3 and 6 months of age for molecular detection of gene sequences. A logistic regression analysis showed differences in detection rates of the stx1 sequence at 3 months, with a higher risk for the non-vaccinated individuals (OR 2.91, CI 1.42–5.94, p = 0.03) and for those born in the cold season (OR 9.55, CI 2.02–45.11, p = 0.004). A Kaplan–Meier survival analysis showed a significant difference in deaths in vaccinated calves compared with non-vaccinated animals (p = 0.018), suggesting that BCG confers non-specific protection during the first 3 months after birth, in field conditions. Full article

IgA nephropathy (IgAN) is the most prevalent type of primary glomerulonephritis, with heterogeneous clinical outcomes. Conventional prognostic factors, such as proteinuria, eGFR, and Oxford histologic classification, have poor sensitivity and specificity. Recently, transcriptomic profiling has been employed to provide insights into the molecular definition of IgAN and facilitate patient stratification in those at risk of disease progression. In this review, we summarize our current understanding of IgAN derived from bulk RNA sequencing, single-cell transcriptomics, spatial transcriptomics, and gene expression profiling to elucidate the molecular characteristics of IgAN. Bulk transcriptomics of glomerular and tubulointerstitial compartments highlighted consistently upregulated genes (e.g., CCL2, CXCL10, LCN2, HAVCR1, COL1A1) and altered pathways (e.g., NF-κB, TGF-β, JAK/STAT, and complement) that are associated with clinical decline. Single-cell and single-nucleus RNA-sequencing has also identified the value of pathogenic cell types and regulatory networks in mesangial cells, tubular epithelium, and immune infiltrates. Furthermore, noninvasive transcriptomic signatures developed from urine and blood may represent useful real-time surrogates of tissue activity. With the advent of integrated analyses and machine learning approaches, personalized risk models that outperform traditional metrics are now available. While challenges remain, particularly related to standardization, cohort size, and clinical deployment, transcriptomics is likely to revolutionize IgAN by providing early risk predictions and precision therapeutics. Unlike prior reviews, our work provides an integrative synthesis across bulk, single-cell, spatial, and noninvasive transcriptomics, linking molecular signatures directly to clinical translation in risk stratification and precision therapeutics. Full article

Cervical cancer is a major global health concern with serious implications for women’s health. It is most often caused by persistent infection with high-risk human papillomavirus (HPV) types. However, about 5–11% of cervical carcinoma cases are HPV-independent, entities with their own unique set of histopathological, molecular, and clinical features. The histopathological forms of HPV-independent cervical cancer include gastric-type adenocarcinoma, clear-cell, mesonephric, and endometrioid carcinoma. Unlike HPV-associated cervical cancers, which require E6 and E7 oncogenes for their expression, HPV-independent tumors exhibit specific mutations such as TP53, PIK3CA, KRAS, STK11, and PTEN. These mutations lead to alternative oncogenic pathways. Diagnosis of HPV-independent cervical adenocarcinoma is often delayed because of possible misclassification as endometrial adenocarcinomas, which frequently results from inadequate HPV testing. This often leads to advanced presentation stages, higher rates of lymphovascular invasion, and, in many cases, a reduced response to chemotherapy and immunotherapy—though outcomes can vary across histotypes and selected patient subgroups—due to the immune-cold tumor microenvironment. Although these morphologic and molecular characteristics describe tumors that are very difficult to manage, PI3K/mTOR and KRAS inhibitors may offer potential therapeutic options for selected patients. This review focuses on the pathogenic and molecular mechanisms, histopathological features, prognosis, and therapeutic difficulties of HPV-independent cervical cancers. Moreover, it provides a comprehension of contemporary issues in diagnostic methods and some new therapeutic approaches, suggesting the need for precision medicine in this aggressive type of cervical cancer. Further studies are necessary to enhance early detection, improve treatment results, and increase survival rates for patients with HPV-independent cervical cancer. Full article

Minimally invasive surgery is known to lessen postoperative stress and complications compared with open procedures, yet its molecular effects on immunity and cancer-related mechanisms remain unclear. This study examined immune and inflammatory responses after robot-assisted (RS) versus open (OS) colorectal cancer surgery. Sixty-one patients (RS = 30; OS = 31) were enrolled. Blood samples were collected before surgery and at 8, 24, and 72 h post-incision. Cytokines, growth factors, and prostanoids were measured using multiplex immunoassays and mass spectrometry to assess systemic immune and inflammatory changes. Surgery type markedly influenced perioperative immune profiles. RS induced stronger activation of Th1-associated cytokines, including IFNγ and IP-10, suggesting enhanced cellular immune responsiveness. In contrast, Th2 cytokines and other immunosuppressive mediators—such as IL-4, IL-10, and G-CSF—showed smaller or transient increases after RS, whereas OS triggered broader and more sustained elevations. Angiogenic factors (VEGF-A, PDGF-BB, FGF2) rose significantly after OS but remained comparatively lower and returned to baseline faster after RS, indicating a weaker proangiogenic response. Similarly, postoperative surges in prostaglandins linked to inflammation and tumor progression (PGE₂, PGF₂α) were blunted and resolved earlier following RS. Overall, the robotic approach was associated with reduced inflammatory and immunosuppressive activity, faster recovery of immune balance, and diminished biochemical signals favoring angiogenesis and potential tumor regrowth, suggesting a potential protective effect against pathogens and cancer-promoting mechanisms after colorectal tumor resection. Full article