Search Results (790)

Background/Objectives: Shikonin (SKN) is a potential anti-psoriatic agent, yet its clinical application is hindered by poor water solubility and low stratum corneum permeability. This study aimed to develop a reactive oxygen species (ROS)-responsive hydrogel microneedle system encapsulating SKN-loaded polymeric micelles (SKN-M@MN) to enhance transdermal delivery and evaluate its therapeutic effects in psoriasis. Methods: Shikonin-loaded micelles (SKN-M) were optimised using a thin-film hydration method. SKN-M@MN was fabricated via a two-step casting method using phenylboronic acid-modified hyaluronic acid (HA-PBA) and polyvinylpyrrolidone K90 as the tip matrix. Skin penetration, ROS-responsive release, and anti-psoriatic efficacy were assessed in an imiquimod (IMQ)-induced mouse model. Mechanistic studies included RNA-seq, qPCR, and Western blotting. Results: SKN-M achieved an encapsulation efficiency of 93.45 ± 0.24%, a particle size of 62.49 ± 0.92 nm, and a zeta potential of −36.78 ± 1.12 mV. SKN-M@MN showed 100% skin penetration, sustained drug release, and accelerated degradation under high ROS conditions. In psoriatic mice, SKN-M@MN significantly alleviated skin lesions, reduced epidermal hyperplasia (Ki67), and downregulated IL-17A and TNF-α levels both locally and systemically. Mechanistically, it inhibited the PI3K/AKT and NF-κB signalling pathways. Conclusions: The SKN-M@MN microneedle platform integrates physical skin penetration, ROS-responsive drug release, and pathway inhibition, offering an effective strategy for transdermal delivery of poorly soluble drugs in psoriasis therapy. Full article

Colorectal cancer (CRC) treatment with standard chemotherapeutics such as capecitabine (CAP) and irinotecan (IRT) is frequently limited by toxicity and resistance. To identify novel adjuvant strategies, we investigated the dichloromethane–methanol (DM) Soxhlet extract of the red alga Jania rubens, previously shown to exert intrinsic antiproliferative effects via reactive oxygen species (ROS) induction, inhibition of epithelial–mesenchymal transition (EMT), and suppression of TET enzymes. The present study evaluated the effect of the DM extract in combination with chemotherapeutic agents in HCT-116, Caco-2, and HT-29 colorectal cancer cell lines, assessing its potential to enhance treatment response. Co-treatment with the DM extract significantly enhanced the cytotoxic and anti-migratory effects of CAP and IRT in HCT-116 and Caco-2 cells. Combination treatment also impaired long-term clonogenic survival, suggesting the inhibition of therapy-resistant subpopulations. Flow cytometric analysis (Annexin V-FITC/PI) revealed a dose-dependent increase in apoptosis in HCT-116 cells following DM treatment. Western blot analysis further supported the pro-apoptotic activity of the DM extract by demonstrating reduced BCL-2 protein expression. The extract additionally modulated the mRNA expression levels of cytokines (TNF-α, IL-6, and IL-10), suggesting potential immunomodulatory effects in colorectal cancer cells. Notably, co-administration of IRT and the DM extract enhanced apoptosis, primarily through the downregulation of the anti-apoptotic gene BCL-2. Together, these findings indicate that the Jania rubens DM extract modulates multiple cellular pathways and enhances the response to conventional CRC chemotherapeutic agents. Full article

Lung cancer represents a substantial global oncology burden, exhibiting mortality rates that surpass those of prostate, pancreatic, and breast cancers. Extensive research has established a correlation between exposure to polycyclic aromatic hydrocarbon mixtures—particularly those containing benzo(a)pyrene (BaP)—and elevated risks of pulmonary and dermal malignancies across various species, including humans. Hesperidin (HSP), a prominent bioactive flavonoid found in citrus fruits and medicinal herbs such as Hypericum perforatum, is recognized for its diverse pharmacological properties. The present study aimed to elucidate the antioxidant and anti-inflammatory efficacy of HSP against BaP-induced toxicity in the A549 non-small cell lung cancer (NSCLC) cell line. Following the determination of application concentrations via MTT assay, the modulatory effects of HSP on cellular proliferation, oxidative stress markers (TAS, TOS, and OSI), and key pro-inflammatory cytokines (TNF−α, IL−1β, and TGF−β) were systematically evaluated. Isolated exposure to BaP predominantly triggered a targeted upregulation of IL-1β; however, hesperidin demonstrated unexpected pro-oxidant dynamics, characterized by a substantial drop in TAS alongside a concurrent elevation in both TOS and OSI profiles, especially at maximum-dose concentrations. Notably, combining BaP with this heightened hesperidin regimen manifested the most severe oxidative distress phenotype, implying a synergistic pro-oxidant cascade between the two agents. On the contrary, minimized concentrations of hesperidin exerted explicit cytoprotective mitigation against the BaP-induced surge in IL-1β, thereby confirming a highly delicate and narrow therapeutic index for this flavonoid. Full article

Excessive use of immunosuppressive agents compromises host immune defenses and broad-spectrum antimicrobial drugs disrupts the normal microbiota, thereby promoting the overgrowth and dissemination of Candida albicans. As an opportunistic pathogen that commonly resides in the intestinal microbiota, C. albicans can subsequently translocate across the intestinal barrier and cause intra-abdominal infections. To investigate this process, a murine model of peritoneal C. albicans infection was established, in which sodium new houttuyfonate was administered for therapeutic evaluation. The therapeutic potential of sodium new houttuyfonate against abdominal C. albicans infection was evaluated through assessment of immune cell composition, peritoneal macrophage polarization, tissue fungal burden, and histopathological features. The molecular mechanisms of sodium new houttuyfonate therapy were also investigated with cellular experiments, including colony counting, real-time quantitative PCR, Western blotting, and the detection of reactive oxygen species (ROS) in RAW264.7 macrophages. Our results revealed that sodium new houttuyfonate exerts a dual anti-infective effect through its fungicidal activity and via the immunomodulation of immunoinflammatory states. Sodium new houttuyfonate also stimulates cytokine production (e.g., IL-1β, IL-6, IL-10, TNF-α, and MCP-1) via the TLR2/p38/NF-κB pathway and promotes the release of ROS and nitric oxide. Overall, these findings highlight the potential of exogenous sodium new houttuyfonate as a therapeutic option for abdominal C. albicans infection. Full article

Gastric cancer is among the leading causes of cancer-related deaths worldwide. Modern treatment approaches include nanoparticles (NPs) designed to target cancer cells, which release a therapeutic cargo facilitating the inhibition of their expansion, thereby improving anti-tumor therapies. The success of NPs, created to deliver anticancer agents and biologically active compounds, may depend on selecting the way to target cancer cells. This study focused on examining the effects of NPs made of polylactic acid (PLA) with histamine (His) end groups and loaded with 5-fluorouracil (5-FU), a known anticancer drug (PLA-His-5-FU), on human gastric cancer AGS cells in vitro. The incubation of AGS cells with PLA-His-FU NPs resulted in diminished mitochondrial membrane potential and the induction of cell apoptosis, along with cell cycle arrest and the reduction of cell proliferation. Furthermore, the NPs tested provoked the secretion of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β by AGS cells and induced the activation of the nuclear factor kappa B (NF-κB) signaling pathway in THP-1 blue monocytes, which indicates the ability to promote the development of a milieu for the infiltration and activation of immunocompetent cells. NPs did not increase intracellular adhesion molecule (ICAM-1) deposition on AGS cells, thus potentially preventing the distribution of cancer cells. In conclusion, PLA-His-5-FU NPs show promising anticancer activity for gastric cancer AGS cells in vitro, better than PLA-OH-5-FU, and can be used in further in vivo studies to confirm this activity. Full article

Inflammatory bowel disease (IBD) is characterized by intestinal barrier dysfunction and excessive inflammation, in which STAT3 signaling plays a critical role. Berberine is clinically effective against colitis; its application is limited by low bioavailability and toxicity. Berberrubine, a major metabolite of berberine, exhibits improved pharmacological properties; however, its therapeutic potential in IBD remains unclear. The efficacy and mechanisms of berberine and berberrubine were evaluated in DSS-induced colitis mice, LPS-stimulated cells and intestinal organoids. STAT3 knockout cell lines were generated using CRISPR-Cas9 to assess the role of STAT3 in mediating the pharmacological activities of both compounds. We found that berberrubine significantly alleviated colitis, reduced pro-inflammatory cytokines (IL-6 and TNF-α), and restored intestinal barrier integrity by upregulating ZO-1 and claudin-1 in vivo and in organoids, demonstrating superior efficacy and safety to berberine. Mechanistically, both compounds inhibited STAT3 activation and nuclear translocation. STAT3 deficiency attenuated their anti-inflammatory, anti-tumor, and barrier-protective effects. Notably, berberrubine exhibited selective cytotoxicity to cancer cells over normal epithelial cells, suggesting a favorable therapeutic window. Collectively, berberrubine ameliorates intestinal barrier dysfunction and inflammation through inhibition of the STAT3 signaling pathway. Its superior efficacy and favorable safety profile compared to berberine support its potential as a novel therapeutic agent for IBD. Full article

Background: Skin photoaging, primarily induced by chronic ultraviolet (UV) radiation exposure, is characterized by dryness, wrinkle formation, pigmentation abnormalities, and reduced skin elasticity, resulting from oxidative stress, inflammation, and degradation of the extracellular matrix. Codonopsis pilosula, a traditional food–medicine homologous plant, is recognized for its anti-aging properties. However, its lipophilic components (designated as CP-L) remain insufficiently explored. Methods: Herein, we developed a thermosensitive nanogel encapsulating CP-L-loaded transferosomes (CP-L nanogel) to enhance topical delivery and evaluated its effects in both a UV-induced photoaging mouse model and UVB-irradiated HaCaT keratinocytes. Results: In UV-induced mice, topical application of the nanogel markedly reduced skin wrinkling and epidermal hyperplasia, with epidermal thickness decreased by 83.2% compared to the model group (p < 0.01), and restored skin elasticity and collagen deposition, as evidenced by a 35.5% increase in collagen area fraction (p < 0.01). Correspondingly, in UVB-irradiated HaCaT cells, it significantly increased cell viability from 53.0 ± 9.6% to 89.4 ± 1.0% (p < 0.01) and suppressed apoptosis from 30.1 ± 0.48% to 12.4 ± 0.66% (p < 0.01). Furthermore, the CP-L nanogel consistently attenuated oxidative stress, with SOD, CAT, and GSH-Px activities increased by 73.1%, 188.1%, and 18.2%, respectively (p < 0.01), and MDA levels reduced by 71.0% (p < 0.01), while inflammatory responses were suppressed, as TNF-α, IL-1α, IL-1β, and IL-6 levels decreased by 28.3%, 22.6%, 12.8% and 31.9%, respectively (p < 0.01). Mechanistically, transcriptomic and molecular analyses revealed that the nanogel potently inhibited the UV-induced activation of the FGFR/PI3K/AKT/mTOR/p70S6K signaling cascade at both transcriptional and protein levels, with the phosphorylation levels of FGFR, PI3K, AKT, mTOR, and p70S6K significantly reduced by 43.9%, 30.9%, 38.8%, 34.9%, and 57.3%, respectively (p < 0.01). Molecular docking and dynamics simulations identified isofuranodienone and aromadendrene oxide-(2) as key constituents with high-affinity, stable binding to FGFR1 and AKT1. The cytoprotective effect of the nanogel was completely abolished by co-treatment with the FGFR inhibitor PD173074, confirming functional reliance on this pathway. Enhanced cellular delivery of the formulation was directly demonstrated by flow cytometry, showing an approximately 1.8-fold increase in cellular uptake compared to the free drug (p < 0.01). Conclusions: Collectively, these results demonstrated that the CP-L nanogel alleviated skin photoaging through a multi-faceted mechanism involving enhanced cellular delivery, potent antioxidant and anti-inflammatory activities, and specific inhibition of the FGFR/PI3K/AKT/mTOR signaling cascade, highlighting its potential as a multitargeted topical agent derived from an edible plant. Full article

Background: Doxorubicin is an effective antineoplastic agent, but its use is constrained by off-target toxicities, including acute liver injury driven by mitochondrial dysfunction, oxidative stress, sterile inflammation, and redox-sensitive signaling pathways. Exenatide, a glucagon-like peptide-1 receptor agonist, exerts antioxidant and anti-inflammatory effects in several experimental liver injury models, but its role in doxorubicin-induced hepatic injury has not been investigated to our knowledge. This study evaluated whether exenatide attenuates acute doxorubicin-induced hepatic injury and examined whether the observed biochemical changes are consistent with modulation of oxidative stress and SIRT1–HMGB1/NF-κB-related signaling. Methods: Male Wistar albino rats were allocated to four groups (n = 7/group): control, exenatide, doxorubicin, and exenatide + doxorubicin. Exenatide (10 µg/kg/day, intraperitoneally) was administered for seven days. Doxorubicin was given intraperitoneally on days 5–7 at a cumulative dose of 18 mg/kg. The pretreatment design was used to test preventive attenuation rather than reversal of established injury. Hepatic injury-associated enzyme activities, serum HMGB1, hepatic SIRT1, NF-κB, TNF-α, IL-6, IL-10, malondialdehyde, glutathione, total antioxidant status, total oxidant status, nitric oxide, and hepatic ^99mTc-pyrophosphate uptake were assessed. Results: Doxorubicin substantially increased intrahepatic ALT and AST activities, serum HMGB1, hepatic NF-κB, TNF-α, IL-6, malondialdehyde, total oxidant status, nitric oxide, and hepatic ^99mTc-pyrophosphate uptake, while reducing SIRT1, IL-10, glutathione, and total antioxidant status. Relative to the doxorubicin group, exenatide lowered HMGB1 by 48.3%, hepatic ^99mTc-pyrophosphate uptake by 48.7%, malondialdehyde by 45.0%, total oxidant status by 37.3%, nitric oxide by 40.7%, NF-κB by 40.4%, TNF-α by 48.6%, and IL-6 by 41.1%, while increasing SIRT1 by 91.7%, IL-10 by 115%, glutathione by 115%, and total antioxidant status by 87.8%. None of the altered parameters returned completely to control levels, indicating attenuation rather than full normalization of acute injury-related changes. Conclusions: Exenatide attenuated doxorubicin-induced acute hepatic injury in this rat model and was associated with reduced oxidative stress, reduced inflammatory activation, higher hepatic SIRT1 levels, lower serum HMGB1 levels, and reduced hepatic ^99mTc-pyrophosphate uptake. The findings are consistent with involvement of SIRT1–HMGB1/NF-κB-related signaling, but they do not establish causality. Hepatic ^99mTc-pyrophosphate uptake should be interpreted as an exploratory imaging correlate of tissue injury rather than an established liver biomarker. Additional studies incorporating histopathology, immunohistochemistry, functional liver indices, mechanistic validation of SIRT1, and tumor-bearing models are required before translational conclusions can be drawn. Full article

Background/Objectives: Psoriasis is a chronic inflammatory skin disease leading to substantial psycho-physical and social burden and reduced quality of life. Biologic agents have transformed its therapeutic landscape. This real-world Italian study described the pattern of treatment with biologic drugs in patients with psoriasis. Methods: A retrospective observational study was conducted using administrative databases from Italian Local Health Units, covering nearly 12 million individuals. The study included adults with psoriasis identified from January 2015 to March 2025 by hospitalization, co-payment exemption code, or topical anti-psoriatic prescriptions. Patients initiating a biologic drug (anti-TNFα, anti-IL12/23, anti-IL17, and anti-IL23) were selected and further analyzed in terms of treatment switching, drug survival, and healthcare resource utilization and related costs within the first year after biologic initiation, and compared. Results: A total of 10,270 biologic-naïve adult patients was included in the analysis (anti-TNFα N = 5078; anti-IL12/23 N = 767; anti-IL17 N = 2574; anti-IL23 N = 1851). Most patients (95.0%) starting an anti-IL23 agent did not switch. Compared with anti-TNFα, initiating an anti-IL23 inhibitor was associated with a significant reduced risk of switching (HR = 0.186; 95%CI: 0.144–0.240; p < 0.001). According to the cost analysis stratified by switching status, remaining on the index biologic was associated with a lower economic burden. Although differences between switchers vs. non-switchers among anti-IL23 users did not reach statistical significance (€12,052 vs. €11,406, respectively, p = 0.132), data support the economic advantage associated with greater treatment stability. Conclusions: Anti-IL23 agents showed effective, durable first-line use with potential long-term clinical and economic benefits in moderate-to-severe psoriasis. Full article

Background/Objectives: Burn injuries in children represent a significant clinical challenge, as current standard-of-care agents such as silver sulfadiazine (SSD) present limitations, including delayed re-epithelialization. This study aimed to evaluate the therapeutic potential of Castanea sativa (sweet chestnut) flower extract—rich in polyphenols and flavonoids with documented antioxidant, anti-inflammatory, and antimicrobial properties but previously uncharacterized in burn wound healing—applied topically on second-degree burn wounds in a juvenile rat model, comparing its efficacy to SSD and their combination. Methods: Forty five-week-old female Wistar albino juvenile rats were randomly allocated into five groups (n = 8): burn control (Group C), SSD monotherapy (Group BS), vaseline vehicle/sham (Group Sham), 5% chestnut flower extract (Group BCs), and SSD combined with extract (Group BSCs). All topical treatments were applied once daily for 14 days. Healing outcomes were assessed by macroscopic wound closure analysis, systemic organ stress markers (ALT, AST, BUN), oxidative stress indices (MDA, SOD, CAT, GPx, GSH), inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10), and histopathological/immunohistochemical analyses (Ki-67, VEGF). Results: All active treatment groups demonstrated significant reductions in organ damage markers, oxidative stress burden, and pro-inflammatory cytokine levels, alongside enhanced antioxidant enzyme activity, compared to Group C (p < 0.001). Extract-treated groups exhibited more pronounced suppression of oxidative and inflammatory parameters than SSD monotherapy. The combination group (BSCs) achieved optimal wound healing outcomes, including near-complete re-epithelialization, superior collagen organization, and prominent angiogenesis, corroborated by the highest Ki-67 proliferation index and VEGF expression scores (p < 0.001). Conclusions:C. sativa flower extract significantly accelerates burn wound healing via antioxidant and anti-inflammatory mechanisms. When combined with SSD, a synergistic effect is observed that overcomes the re-epithelialization delays associated with SSD monotherapy. These findings support C. sativa flower extract as a promising candidate for further preclinical and clinical investigation in pediatric burn management, supporting the ethnopharmacological relevance of this plant in traditional wound care practices; further safety and efficacy validation is required before clinical translation. Full article

Background/Objectives: Resveratrol, a natural polyphenol with anti-inflammatory and antioxidant properties, has emerged as a promising adjunctive agent in periodontal therapy. This systematic review and meta-analysis evaluated evidence from in vitro, in vivo, and human clinical studies regarding the effects of resveratrol on periodontal disease, with the clinical component focusing on systemically healthy non-smoking patients. Methods: Electronic searches of MEDLINE/PubMed, Scopus, Embase, and Web of Science were conducted for studies published between 2000 and 2025. Eligible studies included periodontal-related in vitro cell models, in vivo experimental periodontitis models, and randomized clinical trials assessing resveratrol as an adjunctive therapy. Data extraction, risk-of-bias assessment, and meta-analyses were conducted in accordance with PRISMA guidelines. Results: Fifteen studies were included (five in vitro, six in vivo, and five human randomized controlled trials). Meta-analysis showed the inhibitory effect of resveratrol on the lipopolysaccharide-induced protein expression of IL-1β, IL-6, TNF-α, and IL-8 in vitro, with low to moderate heterogeneity. In animal studies, resveratrol significantly attenuated ligature-induced dental alveolar bone loss, IL-1β protein, and relative mRNA expression. However, reductions in relative mRNA expressions of TNF-α and IL-6 were inconsistent and highly heterogeneous; in contrast, nanoparticle- and liposomal-modified resveratrol consistently and significantly reduced these mRNA levels. In human trials, adjunctive resveratrol was associated with improvements in probing pocket depth and clinical attachment level compared with root planing alone in patients with periodontitis, as well as reductions in bleeding and plaque indices in patients with periodontal diseases, including gingivitis and periodontitis. Conclusions: Resveratrol suppresses pro-inflammatory cytokine expression in vitro and attenuates alveolar bone loss in vivo, with enhanced and more consistent molecular effects observed using modified formulations. Preliminary clinical evidence suggests that resveratrol may be associated with modest adjunctive effects on periodontal outcomes in systemically healthy non-smokers. However, given the limited number of clinical trials, small sample sizes, heterogeneity among studies, short follow-up periods, and limited certainty of the evidence, these findings should be interpreted cautiously. Further well-designed RCTs with longer follow-up periods are required to determine their clinical relevance. Full article

Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, restores hyperglycemic conditions in patients with type 2 diabetes and has recently shown promising anti-inflammatory properties. In this study, we explored its potential to suppress osteoclast formation and bone loss triggered by lipopolysaccharide (LPS), an inflammatory agent. In animal models, the co-administration of liraglutide with LPS on the calvaria regions in mice markedly reduced osteoclast numbers and bone resorption areas relative to treatment with LPS alone. Furthermore, the expression levels of receptor activators of the NF-κB ligand (RANKL) and tumor necrosis factor (TNF)-α mRNA were notably lower in the group receiving liraglutide and LPS compared to treatment with LPS alone. Moreover, in vitro tests revealed that liraglutide has no direct inhibitory effect on RANKL-induced osteoclastogenesis and TNF-α-induced osteoclastogenesis. In addition, liraglutide had no direct inhibitory effect on LPS-stimulated RANKL expression in osteoblasts. Moreover, liraglutide effectively suppressed TNF-α mRNA expression in macrophages stimulated by LPS. These findings suggest that liraglutide prevents inflammatory bone destruction not by targeting osteoclast formation directly but by inhibiting the production of TNF-α within macrophages. Full article

Diarrhea significantly impacts livestock and poultry health, causing growth delays and higher mortality rates. Macleaya cordata extract (MCE) demonstrates strong antioxidant, antibacterial, and anti-inflammatory properties, indicating its potential as a therapeutic agent for diarrhea. This research investigated whether MCE alleviates lipopolysaccharide (LPS)-induced diarrhea in mice through modulation of the gut microbiota. Here, changes in short-chain fatty acids (SCFAs) and gut bacterial structure were analyzed using gas chromatography–mass spectrometry (GC-MS) and 16S rRNA gene sequencing, respectively. The effects of MCE administration (40 mg/kg) on intestinal injury and inflammatory responses were assessed in mice induced with LPS. These results show that MCE-treated mice exhibited significantly lower diarrhea indices, attenuated duodenal villus shortening, and decreased crypt depth compared with LPS-induced mice. MCE treatment substantially reduced the mRNA expression of IL-6, IL-1β and NF-κB in the duodenum, as well as the serum levels of TNF-α and IL-8. Furthermore, MCE significantly increased SCFA levels, particularly acetic acid, and reshaped the gut microbiota composition by increasing the abundance of Lachnospiraceae. Given the close interaction between gut microbiota, microbial metabolites, and host inflammatory responses, these microbial and metabolic alterations are closely associated with the attenuation of intestinal and systemic inflammation. In conclusion, the protective effects of MCE against LPS-induced diarrhea in mice are closely associated with the modulation of gut microbiota structure, suppression of inflammatory responses, and enhancement of acetic acid production. This study provides a mechanistic basis for MCE as a natural alternative to antibiotics for treating inflammatory diarrhea in livestock and poultry. Full article

Background/Objectives: The Systemic Immune–Inflammation Index (SII), derived from routine blood counts, has emerged as a potential marker of systemic inflammation in psoriasis. However, its longitudinal behavior across different systemic and biologic therapies remains poorly characterized. This study aimed to evaluate changes in SII over time, assess its relationship with Psoriasis Area and Severity Index (PASI) scores, and compare SII trajectories among different treatment classes. Methods: A retrospective single-center study included 210 adults with psoriasis treated for 12 months with cyclosporine, anti-TNF-α, anti-IL-17, or anti-IL-23 agents. SII and PASI were recorded at baseline, 16, 36, and 52 weeks. Correlations between SII and PASI were assessed using Spearman’s analysis. Longitudinal changes were evaluated using the Friedman test, and treatment-group differences were assessed using Kruskal–Wallis analysis. An adjusted multivariable linear regression model including age, sex, body mass index, psoriatic arthritis, baseline PASI, and treatment group was performed to identify factors associated with Δ%SII. Results: SII correlated with PASI at baseline (ρ = 0.406, p < 0.001) and at 52 weeks (ρ = 0.186, p = 0.007), whereas no significant associations were observed at intermediate timepoints. Longitudinal analyses demonstrated significant differences in SII trajectories among treatment groups (p < 0.001). SII increased over time in the cyclosporine and anti-TNF-α groups, while anti-IL-17 and anti-IL-23 therapies were associated with marked and sustained reductions. In the adjusted model, anti-IL-17 (β = −90.7, 95% CI −119.6 to −61.8, p < 0.001) and anti-IL-23 therapies (β = −97.9, 95% CI −126.2 to −69.6, p < 0.001) remained independently associated with greater reductions in SII compared with cyclosporine, whereas anti-TNF therapy showed no significant difference. Conclusions: SII is a dynamic marker of systemic inflammatory changes in psoriasis and exhibits distinct longitudinal patterns according to treatment class. The pronounced reductions observed with IL-17 and IL-23 inhibitors support the potential value of SII as an adjunctive measure of systemic inflammation. However, prospective studies are required to clarify its clinical utility and determine its role in routine patient management. Full article

Major depressive disorder (MDD) is a complex and heterogeneous psychiatric disorder with a high prevalence. Neuroinflammation may define biologically distinct patient subgroups with different mechanisms, clinical phenotypes, and treatment responses. This narrative review integrates current evidence around three linked questions: how neuroinflammatory processes contribute to depression, how biomarkers can identify clinically relevant inflammatory phenotypes, and how these findings can inform anti-inflammatory treatment strategies. The major mechanisms discussed include microglial activation and neuroimmune signaling, hypothalamic–pituitary–adrenal axis dysregulation and glucocorticoid receptor resistance, kynurenine pathway alterations, and cytokine-driven impairment of neurogenesis and synaptic plasticity. These pathways interact with stress responses, neurotransmitter systems, and neuronal function, while their expression may vary according to sex, age, hormonal status, disease stage, and treatment exposure. These interconnected pathways may contribute to depressive symptoms by disrupting neurotransmitter systems and impairing neural plasticity. In addition, this review discusses several candidate biomarkers, including C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF) and transforming growth factor-β1 (TGF-β), which may support patient stratification, treatment prediction, and assessment of target engagement. Clinical trials of anti-inflammatory agents have shown inconsistent and generally modest effects in unselected MDD populations. By integrating mechanistic evidence with biomarker-guided therapeutic implications, this review aims to clarify how neuroinflammatory research may inform more precise and individualized treatment strategies for depression. Full article