Search Results (197)

Polycystic ovary syndrome (PCOS) is frequently accompanied by visceral obesity, insulin resistance, low-grade chronic inflammation, and metabolic syndrome (MetS). These alterations promote significant dysfunction in adipose tissue and liver metabolism through cytokine production. Growing evidence indicates that the interaction between hepatokines and adipokines plays a central role in the development of metabolic and hepatic abnormalities in women with PCOS. This narrative review was conducted to analyze the relationship between adipose tissue dysfunction and liver metabolic impairment in women with PCOS, emphasizing the involvement of hepatokines and adipokines in insulin resistance, inflammation, hepatic steatosis, hepatic fibrosis and MetS. From this perspective, contemporary clinical, biochemical, and molecular studies were reviewed to evaluate how adipocyte-derived factors and hepatocyte-derived cytokines influence metabolic homeostasis in the liver and adipose tissue in women with PCOS. Increased visceral adiposity in PCOS enhances the release of free fatty acids (FFAs) to the liver, resulting in hepatotoxicity, oxidative stress, and hepatic inflammation. Several hepatokines, including fetuin-A, angiopoietin-like protein 3 (ANGPTL3), selenoprotein P(Sep-P), and hepassocin (HPS), show abnormal circulating levels in PCOS and are strongly associated with insulin resistance, dyslipidemia, and progression to hepatic steatosis. In contrast, fibroblast growth factor 21 (FGF-21), follistatin, and interleukin (IL-6) may exert dual effects. Adipokines, such as resistin, visfatin, apelin, and retinol-binding protein 4 (RBP-4), contribute to chronic inflammation, impaired glucose metabolism, androgen excess, and hepatic steatosis and fibrosis. Some of these adipokines, such as leptin and vaspin, may exert both beneficial and detrimental effects, while others, including chemerin and omentin, appear to play predominantly beneficial roles in metabolism. Reduced adiponectin-to-leptin levels further aggravate metabolic dysfunction. These changes indicate that adipose tissue–liver crosstalk is a key mechanism linking PCOS and MetS. Overall, metabolic disturbances in PCOS are strongly mediated by dysregulated communication between adipose tissue and the liver. Altered hepatokine and adipokine profiles contribute to insulin resistance, liver dysfunction, hypertension and the development of MetS in women with PCOS. Understanding these intricate interactions may support the early identification of high-risk patients and the development of targeted therapeutic strategies. Full article

Background: Fracture healing requires a coordinated inflammatory response, and its dysregulation, as seen in polytrauma, can impair bone regeneration. Human mesenchymal stem cells (hMSCs) play a central role in fracture repair through osteogenic differentiation and also via their secretome, which regulates local inflammation, angiogenesis, and tissue regeneration. Interleukin-6 (IL-6), an early pro-inflammatory cytokine, contributes to fracture healing by promoting MSC recruitment and osteogenic differentiation, whereas bone morphogenetic protein-2 (BMP-2) is a key osteoinductive factor that drives bone formation. However, the combined effects of IL-6 and BMP-2 on the hMSC secretome remain poorly understood. Methods: We cultured hMSCs in osteogenic media supplemented with recombinant IL-6 (1–20 ng/mL) alone or combined with recombinant BMP-2 (1 ng/mL) on tissue culture plastic (TCP) and within gelatin methacryloyl (GelMA) hydrogels of low (~3 kPa), medium (~15 kPa), and high (~30 kPa) stiffness. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity and calcium deposition; cytokine profiling was performed using a multiplex antibody array. Results: When cultured on TCP, IL-6 suppressed ALP activity by day 21. Co-treatment with IL-6 and BMP-2 induced a dysregulated secretome with concurrent upregulation of pro-inflammatory markers (MIP-1α, TNF-α, and GM-CSF) and anti-inflammatory mediators (IL-10, TGF-β1, and VEGF). This hyperinflammatory response was attenuated when hMSCs were encapsulated in GelMA, with high-stiffness gels most effectively suppressing pro-inflammatory chemokines and medium-stiffness gels yielding the highest ALP activity. Conclusions: These findings suggest that mechanically tuned GelMA hydrogels modulate immune and osteogenic responses of hMSCs in vitro, warranting further investigation in the context of scaffold design for fracture care. Full article

Platelet-rich gel supernatants (PRGS) are increasingly used in veterinary medicine due to their regenerative and immunomodulatory properties; however, most studies focus on individual mediators and provide limited insight into their coordinated biological behavior. This study aimed to characterize the integrated inflammatory–regenerative signatures of bovine PRGS stored under different temperature conditions using a multivariate approach. Concentrations of transforming growth factor beta-1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2), and interleukin-6 (IL-6) were evaluated in PRGS samples from six clinically healthy cows stored at −80, −20, 4, 21, and 37 °C for up to 326 h. Data were standardized and explored using hierarchical clustering and heatmaps, and principal component analysis (PCA) based on area under the concentration–time curve (AUC) was used to integrate temporal behavior. Temperature-dependent multivariate signatures were identified, with frozen PRGS clustering separately from samples stored at moderate temperatures. The first two principal components explained 43.0% and 28.9% of the variance and defined an inflammatory–regenerative gradient contrasting TGF-β1/IL-2 versus TNF-α/IL-6 profiles. Linear mixed-effects modeling showed that PC1 was significantly affected by temperature and time (p < 0.001), whereas PC2 was influenced by temperature, time, and their interaction (p ≤ 0.048). Differences among temperatures were minimal at early time points but became more pronounced from 48 to 96 h onward, following a temperature gradient with higher values at moderate temperatures and lower values under frozen conditions. These findings indicate that storage temperature reshapes the integrated biological profile of PRGS, rather than merely preserving mediator composition. Full article

Background/Objectives: Obesity is characterized by chronic low-grade inflammation, and bariatric surgery promotes substantial metabolic and inflammatory improvement. However, residual obesity and microvascular complications may persist in some individuals, suggesting potential genetic influences on postoperative outcomes. This exploratory pilot study investigated the association between inflammatory cytokine gene polymorphisms and clinical, metabolic, and inflammatory outcomes in older women one year after bariatric surgery. Methods: This cross-sectional, hypothesis-generating pilot study included 21 women aged ≥50 years (mean 61.6 ± 5.0) who underwent Roux-en-Y gastric bypass at a public bariatric center in Brazil. Anthropometry, body composition, biochemical markers, and serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were assessed 12 months postoperatively. Genotyping for IL6-174G/C (rs1800795) and TNFA-308G/A (rs1800629) was performed using PCR-RFLP. Associations were analyzed using non-parametric statistical tests. Results: Notably, the IL6-174CC genotype was associated with persistent obesity, whereas carriers of the TNFA-308A allele showed a higher prevalence of diabetic retinopathy. These results highlight genotype-specific postoperative outcomes. No significant genotype-related differences were observed for most anthropometric, biochemical, or inflammatory parameters, indicating substantial overall metabolic improvement after surgery regardless of genetic background. However, the observed associations were based on a small sample and should be interpreted cautiously. Conclusions: This exploratory pilot study revealed associations between inflammatory cytokine gene polymorphisms and selected postoperative outcomes, particularly persistent obesity and diabetic retinopathy, in older women one year after bariatric surgery. These hypothesis-generating findings emphasize the need for larger, longitudinal studies to clarify the role of genetic factors in postoperative heterogeneity after bariatric surgery. Full article

Background/Objective: This study evaluated the analgesic and anti-inflammatory effects of ambroxol in an experimental model of endometriosis. Methods: Ambroxol was administered at doses of 10, 50, and 100 mg/kg (Abx 10, Abx 50, and Abx 100) by daily gavage for 21 days. A medroxyprogesterone-treated group (Progesterone) was included as a positive control. Pain was assessed using validated behavioral tests, including the Rat Grimace Scale (RGS), the von Frey test, and the rotarod test. Additionally, interleukin-1β (IL-1β) levels and total leukocyte counts were measured in peritoneal lavage fluid. The volumetric reduction in endometriotic implants was evaluated by ultrasonography, while histopathological analysis characterized inflammatory infiltrate and epithelial layer integrity using a standardized scoring system. Results: All ambroxol doses reduced spontaneous pain manifestations throughout the treatment. The mechanical withdrawal threshold significantly increased from the second week onward, and motor quality improved over the course of the study. A significant reduction in IL-1β levels compared with the negative control (Control(−)) was observed on day 21. Abx 50 and Abx 100 significantly reduced implant volumes (48.2% and 56.2%, respectively) and promoted marked disruption of the endometriotic epithelial layer. When compared with Progesterone, higher doses—particularly 100 mg/kg—demonstrated comparable efficacy. Conclusions: Taken together, these pleiotropic effects support the potential for drug repurposing in endometriosis. Full article

Excessive macrophage activation is thought to be the primary cause of the cytokine storm that results in severe coronavirus disease 2019 (COVID-19) complications. The underlying mechanisms remain elusive, and more research is needed to find disease-critical genes and develop effective therapies. In this study, we used publicly accessible microarray datasets of cytokine storm in cultured human monocyte-derived macrophages challenged with cytokines, and employed bioinformatics, such as weighted gene co-expression network analysis (WGCNA) and differential expression analysis, to dissect gene expression profiles and identify putative disease-related molecules. Initially, three co-expression modules and related key genes were discovered, which highly correlated to macrophages challenged with cytokines. Then, a preliminary gene expression signature consisting of 203 upregulated and 24 downregulated genes was identified. Next, protein–protein interaction analysis and hub gene identification were used to identify 11 crucial hub genes, namely tripartite motif-containing 21 (TRIM21), interferon regulatory factor 1 (IRF1), guanylate binding protein 1 (GBP1), transporter associated with antigen processing 1 (TAP1), nuclear myosin I (NMI), interleukin 15 receptor subunit alpha (IL15RA), apolipoprotein L1 (APOL1), intercellular adhesion molecule 1 (ICAM-1), protein tyrosine phosphatase non-receptor type 1 (PTPN1), E74-like ETS transcription factor 4 (ELF4) and guanylate binding protein 2 (GBP2). Then, the LINCS L1000 characteristic direction signatures search engine (L1000CDS2) was employed for drug repurposing studies. Dasatinib was predicted to be the leading therapeutic compound to perturb the gene signature of cytokine storm in human macrophages. Connectivity Map results suggested that dasatinib may normalize ICAM-1 expression. In addition, the results of molecular docking studies and molecular dynamics simulation revealed that dasatinib may spontaneously interact with ICAM-1 via several key residues and form a relatively stable protein–ligand complex. Overall, this work, based on an analysis of co-expression correlation networks, gene expression signatures and pivotal genes in human macrophages challenged with cytokines, combined with drug repurposing studies, demonstrated that dasatinib may interact with ICAM-1 and could be a potential candidate for cytokine storm. However, due to the limitations of computational approaches, further experimental validation is necessary. Full article

Background/Objectives: The high prevalence of obesity and obesity-associated diseases in the United States and worldwide places a tremendous burden on public health. Although lifestyle interventions, such as calorie-restricted diets and increased exercise, are generically recommended to individuals with overweight and obesity, it is well acknowledged that individual responses to the same lifestyle intervention vary significantly, underscoring the importance of individualized or precision nutrition-based approaches in obesity management. Methods: In a recent randomized, parallel-arm pilot study, manuka honey (21 g) was given daily to overweight and obese participants aged 40–75 years for four weeks. The levels of plasma interleukin (IL)-6 at the baseline and after honey treatment were measured. The 14 female participants were stratified into responder (R) and non-responder (NR) groups, based on their circulating IL-6 level changes. Plasma and fecal samples from the R and NR groups were subjected to untargeted metabolomics analysis and 16S rRNA analysis, respectively. Results: Among the female participants with overweight and obesity, 50% had reduced plasma levels of IL-6 after honey intake, and other 50% showed no such responses. Untargeted metabolomics analysis demonstrated that 22 metabolites markedly increased and eight decreased in the R group, relative to the NR group. A decrease in circulating glutamic acid could potentially predict the responsiveness to honey intake. 16S rRNA analysis showed that 23 and 14 genera were uniquely enriched in the R and NR groups, respectively. Enriched Bacteroides and Akkermansia in the R group are capable of metabolizing glutamic acid and thus may contribute to the decreased level of circulating glutamic acid. Conclusions: In this pilot study, participants with overweight and obesity showed different responses to honey intake. Circulating glutamic acid may have the potential to predict the responsiveness of patients to honey and provide guidance for precision nutrition-based dietary intervention. Full article

Background: Dry Eye Disease (DED) is a multifactorial disorder characterized by tear film instability and ocular surface inflammation. Murine models based on environmental stress are widely used to mimic evaporative DED, although many focus on limited disease features. This study aimed to provide an integrated characterization of ocular surface alterations induced by chronic desiccating stress. Methods: Adult mice were housed in a Controlled-Environmental Chamber (CEC) with low humidity and increased airflow for up to 21 days and sacrificed after 14 or 21 days. Corneal damage was assessed by fluorescein staining. Conjunctival histology was evaluated for epithelial morphology, goblet cell (GC) size, and mucin composition. Complement fractions C3 and C5a were assessed by immunohistochemistry. Expression of inflammatory markers (Major Histocompatibility Complex, Class II, DR, HLA-DR; interleukin-1β, IL-1β; tumor necrosis factor-α, TNF-α) was quantified by Real-Time PCR (RT-PCR) in corneal and conjunctival epithelium. Results: Fluorescein staining revealed progressive corneal epithelial damage over time. Histological analysis demonstrated conjunctival epithelial alterations characterized by a significant reduction in GC size and in neutral mucin-positive GCs, consistent with mucin remodeling of the ocular surface epithelium. Increased epithelial deposition of complement fractions C3 and C5a was observed, while molecular analysis confirmed upregulation of inflammatory markers, including HLA-DR, IL-1β, and TNF-α. Collectively, these findings indicate that the model captures key pathophysiological components of DED. Conclusions: The CEC model reproduces major features of evaporative DED, including epithelial damage, GC remodeling, immune activation, and inflammation. As a non-invasive desiccating stress model, it represents a relevant experimental platform for studying ocular surface inflammation and for preclinical evaluation of therapeutic strategies. Full article

Background/Objectives: Pulmonary fibrosis is a chronic, progressive lung disease marked by scarring and inflammation, leading to impaired respiratory function. This study aimed to investigate the combined therapeutic effects of pirfenidone (PFD), metformin (MET), and bone marrow-derived mesenchymal stem cells (BM-MSCs) on bleomycin (BLM)-induced pulmonary fibrosis in rats. Methods: Forty-eight Western Albino rats were divided into six groups: normal control, BLM-positive control, and four treatment groups receiving PFD, MET, BM-MSCs, and their combination. Treatments were administered for four weeks starting on day 21 post-BLM instillation. Lung tissues were analyzed for oxidative stress markers, inflammatory cytokines, apoptotic markers, and fibrogenic gene expression. Histopathological changes were assessed using hematoxylin and eosin (H&E) and Masson’s trichrome staining. Results: The combination therapy significantly reduced oxidative stress and inflammatory markers while enhancing antioxidant capacity. It decreased pro-apoptotic Bcl-2-associated X protein (BAX) and increased anti-apoptotic B-cell lymphoma 2 (Bcl-2) levels. Additionally, anti-inflammatory interleukin-10 (IL-10) was elevated, while tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta 1 (TGF-β1) levels were markedly lowered. Gene expression analysis showed a significant downregulation of matrix metalloproteinase-9 (MMP-9) and collagen type 1 alpha 1 (Col1α1). Histologically, the combination treatment group exhibited minimal fibrosis and inflammation, closely resembling normal lung tissue. Conclusions: The combination of PFD, MET, and BM-MSCs offered superior therapeutic efficacy in treating BLM-induced pulmonary fibrosis compared to individual treatments. This multimodal approach effectively targets oxidative stress, inflammation, apoptosis, and fibrosis, suggesting strong potential for future clinical application. Full article

This study aimed to investigate the impacts of chestnut tannin (CT) on growth performance, immune response, and intestinal health of broilers challenged with necrotic enteritis (NE) through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-ferroptosis pathway. A total of 240 one-day-old male Cobb 500 broilers (44.54 ± 0.51 g) were randomly divided into four groups, including a Control group, NE group, 500 mg/kg CT group (L-CT), and 1000 mg/kg CT group (H-CT), with six replicates per group and ten broilers per replicate. Sporulated coccidia oocysts on day 14 and Clostridium perfringens solution from days 19 to 21 were given to all broilers except the Control group through oral administration to establish the NE infection model. The results demonstrated that dietary supplementation with CT improved (p < 0.05) growth performance, intestinal morphology, and intestinal mucosal barrier function of broilers challenged with NE. CT supplementation decreased (p < 0.05) interleukin (IL)-1β, IL-6, type I interferon, interferon-γ, and tumor necrosis factor-α concentrations and increased (p < 0.05) IL-10 concentration in the jejunal mucosa. Furthermore, CT supplementation decreased (p < 0.05) Fe²⁺ concentration, malondialdehyde concentration, mitochondrial DNA level, and mitochondrial reactive oxygen species level in the jejunal mucosa. Broilers under NE challenge had upregulated (p < 0.05) jejunal protein expression of cGAS, STING, phospho-TANK-binding kinase 1, phospho-interferon regulatory factor 7, phospho-nuclear factor kappa B, ferroptosis suppressor protein 1, prostaglandin-endoperoxide synthase 2, acyl-CoA synthetase long-chain family member 4, WD repeat domain phosphoinositide-interacting protein 2, nuclear receptor co activator factor 4 and autophagy related protein 5 and downregulated (p < 0.05) glutathione peroxidase 4, ferritin heavy chain 1, ferritin light chain and ferroportin 1 compared with the Control group, while the supplementation of CT reversed these effects. In conclusion, CT improved intestinal inflammatory damage of broilers challenged with NE by inhibiting the cGAS-STING-ferroptosis pathway, which was more effective at a dose of 1000 mg/kg in this study. Full article

Background: The emergence of coccidial drug resistance has intensified the search for sustainable, residue-free solutions to control poultry coccidiosis. This challenge has positioned plant essential oils as promising candidates among the priority research areas. The study aimed to investigate the efficacy of essential oils in improving immune function and intestinal health in white-feathered broilers challenged with a high-dose coccidial vaccine. Methods: A total of 480 one-day-old broilers were randomly assigned to five treatments: uninfected (CON), infected (EC), infected + 500 g/t narasin (AT), and infected + 200 or 400 g/t essential oil blend (EOB200 or EOB400). There were 6 replicates per treatment and 16 broilers per replicate. All infected treatments received a 30-fold coccidial vaccine on d 14. The CON group was administered an equal volume of sterile normal saline on d 14 of the experiment. One bird per replicate was sampled on d 22, and the remainder were raised until d 42. Results: Results showed that the challenge increased the fecal oocyst counts on d 21 and 28 and elevated intestinal lesion scores and serum interleukin-6 (IL-6) levels on d 21, while it decreased IL-10 levels on d 21 and reduced the villus height-to-crypt depth (V:C) ratio in the duodenum and jejunum (p < 0.05). Additionally, compared with the EC group, the AT, EOB200, and EOB400 groups reduced oocyst excretion and serum superoxide dismutase (SOD) (p < 0.05). The EOB200 group also showed the highest serum transforming growth factor-β (TGF-β) concentration, along with the lowest immunoglobulin G (IgG) level (p < 0.05). Moreover, within the infected groups, the EOB200 group exhibited the highest duodenal villus height and V:C ratio (p < 0.05). Conclusions: These findings indicated that the EOB200 and EOB400 groups alleviated intestinal damage caused by the coccidial vaccine with an efficacy comparable to that of antibiotics, and the EOB200 group exhibited a superior effect. The results confirm that the essential oil blend holds great application potential as an alternative to antibiotics. Full article

Cytomegalovirus (CMV) seropositivity associates with cardiovascular disease in healthy adults, but associations are unclear in people living with HIV (PLWH) despite their high CMV burden. However, CMV antibody levels correlated with inflammatory biomarkers only in PLWH who subsequently developed coronary artery disease (CAD), so the effects of CMV in an individual may vary. Here we investigate the role of CMV-encoded interleukin-10 (cmvIL-10) in PLWH on anti-retroviral therapy. Plasma levels of cmvIL-10 and antibodies reactive with a cmvIL-10 peptide or a lysate of CMV-infected fibroblasts were assessed in PLWH with or without CAD. cmvIL-10 was assessed at diagnosis/selection (T0) and 12 months earlier (T-12), with anti-cmvIL-10 also assessed at −24 and −36 months (n = 36–58/group). Plasma cmvIL-10 was recorded as positive in 5–10 PLWH per group, irrespective of CAD status. Of 21 PLWH with detectable cmvIL-10, only six were positive at both timepoints. Anti-cmvIL-10 was measurable in all samples, at levels independent of cmvIL-10, CAD or time of sampling. Amongst PLWH without CAD, the detection of cmvIL-10 associated with higher levels of CXCL10 (T0 and T-12) and lower levels of the IL-1 receptor antagonist (IL-1Ra; T0 only). At T-12, anti-cmvIL-10 correlated with IL-1Ra in PLWH without CAD (p = 0.01), and sCD14 in PLWH with CAD (p = 0.01). Anti-cmvIL-10 correlated with VCAM-1 at several timepoints in both groups. Hence, cmvIL-10 may be produced episodically, inducing anti-cmvIL-10 peptide antibody, which may represent levels of the cytokine averaged over time. Plasma levels of cmvIL-10 and anti-cmvIL-10 antibody associated differently with inflammatory biomarkers in PLWH with and without CAD, suggesting mechanisms by which host responses to CMV may have different clinical consequences. Full article

Insulin resistance develops when skeletal muscle (SM), adipose tissue (AT), and the liver fail to respond adequately to insulin, a dysfunction closely intertwined with chronic low-grade inflammation. This combination leads to compensatory hyperinsulinemia, dysglycemia, and metabolic stress, driving major disorders such as type 2 diabetes, metabolic syndrome, metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular disease. Both adipokines and myokines are central modulators of this metabolic–inflammatory axis. In obesity, diabetes, MASLD, and thyroid dysfunction, alterations in myokines such as myostatin, irisin, fibroblast growth factor 21 (FGF-21), apelin, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and interleukin-15 (IL-15) influence glucose uptake, lipid oxidation, mitochondrial function, and systemic inflammation. Exercise-induced myokines exert insulin-sensitizing and anti-inflammatory effects, whereas myostatin and tumor necrosis factor-alpha (TNF-α) promote metabolic impairment. These pathways reveal extensive crosstalk between SM and key metabolic organs—including the liver, pancreas, AT, intestine, heart, and thyroid gland. In metabolic disease, inflammation-driven changes in deiodinase activity and triiodothyronine (T3) availability further link muscle dysfunction with thyroid imbalance. The aim of this narrative review was to elucidate the complex interplay between myokines, adipokines, inflammation, and insulin resistance, and to clarify their clinical relevance in metabolic and thyroid disorders. Given this integrative role of SM, sarcopenia should be recognized as a clinical marker of metabolic or thyroid dysregulation, and preserving muscle mass through structured physical activity should be a core therapeutic target. Full article

Weaned piglets have a fragile gastrointestinal tract and immature digestive function. Supplementation of Bacillus can enhance intestinal barrier function and improve nutrient digestion and absorption efficiency. It is an important nutritional regulation method to alleviate weaning stress, reduce the incidence of diarrhea and promote growth performance. This experiment was conducted to investigate the effects of Bacillus subtilis, Bacillus pumilus and their combination on growth performance, diarrhea incidence, nutrient apparent digestibility, intestinal morphology and barrier function of weaned piglets. A total of 128 weaned piglets weighing 6.68 kg (±0.35 kg) were selected, divided into 4 treatment groups, and fed with a basal diet (CTR), a Bacillus subtilis (BS1), a Bacillus pumilus (BS2) and a Bacillus subtilis + Bacillus pumilus (BS1 + BS2) for 42 days. Each group had 8 replicates with 4 piglets per replicate. One piglet was selected from each replicate and euthanized to collect intestinal samples. The results showed that compared with the CTR group, the BS1 + BS2 group significantly increased the average daily gain (ADG) of weaned piglets on days 0–14 (p < 0.05), and the BS2 group significantly increased the ADG on days 0–42 (p < 0.05). Compared with the CTR group, the BS1 + BS2 group significantly reduced the full-time diarrhea rate (p < 0.05), and weaned piglets of the BS2 group significantly reduced the incidence of diarrhea on days 0–14, 15–28, and 0–42 of the study, in comparison to the control (p < 0.05). Compared with the CTR group, the piglets in the BS1 + BS2 group significantly decreased the serum tumor necrosis factor-α (TNF-α) content on day 21 (p < 0.05), and the BS1, BS2, and BS1 + BS2 groups significantly decreased the serum TNF-α content on day 42 (p < 0.05). Compared with the CTR group, the BS1 + BS2 group significantly reduced the expression of Interleukin-8 (IL-8) mRNA in the ileum (p < 0.05). The BS1, BS2, and BS1 + BS2 groups significantly reduced the expression of TNF-α mRNA in the ileum, IL-8 mRNA in the jejunum, and TNF-α mRNA in the jejunum (p < 0.05). In addition, compared with the CTR group, the BS2 and BS1 + BS2 groups significantly increased Claudin-1 mRNA expression in the jejunum (p < 0.05). Compared with the CTR group, the BS1 and BS2 groups significantly increased Occludin mRNA expression in the jejunum (p < 0.05). In summary, dietary supplementation with Bacillus-based probiotics can significantly improve growth performance in weaned piglets, reduce diarrhea incidence, alleviate inflammation, and enhance intestinal barrier function. Full article

Tendon injuries present significant clinical challenges due to limited intrinsic healing and complex pathological mechanisms. Here, we developed a novel 3D bioprinted methacrylated type I collagen (ColMA) scaffold integrated with Growth Differentiation Factor-5 (GDF-5)-loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticles and dynamically cultured it under perfusion to establish a tenogenic microenvironment in vitro. Pathological human Tendon Stem/Progenitor Cells (hTSPCs) derived from tendinopathic surgical explants were encapsulated to investigate their impaired extracellular matrix (ECM) deposition and associated pro-inflammatory signaling. GDF-5-loaded nanoparticles (average diameter 140 ± 40 nm) were fabricated via microfluidic-assisted nanoprecipitation and homogeneously incorporated within the ColMA synthetic ECM to enable sustained growth factor release. Continuous perfusion culture (1 mL/min) ensured efficient mass transfer and supported cell viability above 70% over 21 days. Pathological hTSPCs exhibited impaired ECM remodeling, characterized by the absence of type I collagen and a 2.56-fold increase in type III collagen at day 7, indicative of a fibrotic-like phenotype. Western blot densitometry demonstrated a 5.31-fold elevation in secreted tenomodulin at day 14, while ECM analysis verified a type III to type I collagen ratio of 4.5. In addition, a markedly pro-inflammatory cytokine profile was observed, with elevated secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8) from day 7 onward, consistent with the chronic inflammatory status of cells derived from pathological tendon tissues. This modular 3D platform represents a robust in vitro model for mechanistic studies and the advancement of personalized regenerative strategies targeting chronic tendon disorders. Full article