Lipopolysaccharide (LPS), a component of the outer membrane of Gram‐negative bacteria, triggers inflammatory responses in intestinal epithelial cells. This activation leads to the production of pro‐inflammatory cytokines which disrupt cellular homeostasis. LPS also impairs the integrity of the intestinal epithelial barrier by downregulating tight junction proteins, resulting in increased intestinal permeability. This compromised barrier function can allow further translocation of luminal antigens, perpetuating inflammation and contributing to gut‐related disorders such as inflammatory bowel disease (IBD) and metabolic endotoxemia. This study investigated the therapeutic effects of inulin, a prebiotic dietary fiber, in attenuating LPS‐induced intestinal epithelial barrier dysfunction. Caco‐2 cells were treated with 100 ng/mL of LPS for 12 h, resulting in increased gene expression of pro‐inflammatory cytokines (IL‐1β, TNF‐α, and IL‐18) and a significant downregulation of tight junction proteins claudin‐1 and claudin‐2, while occludin gene expression remained unaffected. Pretreatment with 2% inulin for 24 h before LPS exposure prevented the downregulation of claudin‐1 and claudin‐2 and significantly upregulated occludin gene expression. These molecular findings were supported by functional assays using transwell systems. LPS treatment increased paracellular permeability of the Caco‐2 monolayer, indicating barrier dysfunction, while inulin pretreatment mitigated this effect. These results demonstrate that inulin can modulate tight junction protein expression and maintain gut barrier integrity under inflammatory conditions.

Salmonella Typhi is an intracellular bacterium causing a variety of enteric diseases, being typhoid fever the most common. Current modalities for treating S. typhi infection are subjected to multi-drug resistance. Herein, a novel macrophage targeting approach was developed via coating bioinspired mannosylated preactivated hyaluronic acid (Man-PTHA) ligands on a self-nanoemulsifying drug delivery system (SNEDDS) loaded with the anti-bacterial drug ciprofloxacin (CIP). The shake flask method was used to determine the drug solubility in the different excipients (oil, surfactants and co-surfactants). Man-PTHA were characterized by physicochemical, in vitro, and in vivo parameters. The mean droplet size was 257 nm, with a PDI of 0.37 and zeta potential of -15 mV. In 72 h, 85 % of the drug was released in a sustained manner, and the entrapment efficiency was 95 %. Outstanding biocompatibility, mucoadhesion, muco-penetration, anti-bacterial action and hemocompatibility were observed. Intra-macrophage survival of S. typhi was minimal (1 %) with maximum nanoparticle uptake, as shown by their higher fluorescence intensity. Serum biochemistry evaluation showed no significant changes or toxicity, and histopathological evaluation confirmed the entero-protective nature of the bioinspired polymers. Overall, results confirm that Man-PTHA SNEDDS can be employed as novel and effective delivery systems for the therapeutic management of S. typhi infection.

Mutations underlying disease in tuberous sclerosis complex (TSC) give rise to tumors with biallelic mutations in TSC1 or TSC2 and hyperactive mammalian target of rapamycin complex 1 (mTORC1). Benign tumors might exhibit de novo expression of immunogens, targetable by immunotherapy. As tumors may rely on ganglioside D3 (GD3) expression for mTORC1 activation and growth, we compared GD3 expression in tissues from patients with TSC and controls. GD3 was overexpressed in affected tissues from patients with TSC and also in aging Tsc2+/ ^– mice. As GD3 overexpression was not accompanied by marked natural immune responses to the target molecule, we performed preclinical studies with GD3 chimeric antigen receptor (CAR) T cells. Polyfunctional CAR T cells were cytotoxic toward GD3-overexpressing targets. In mice challenged with Tsc2 ^–/– tumor cells, CAR T cells substantially and durably reduced the tumor burden, correlating with increased T cell infiltration. We also treated aged Tsc2+/ ^– heterozygous (>60 weeks) mice that carry spontaneous Tsc2 ^–/– tumors with GD3 CAR or untransduced T cells and evaluated them at endpoint. Following CAR T cell treatment, the majority of mice were tumor free while all control animals carried tumors. The outcomes demonstrate a strong treatment effect and suggest that targeting GD3 can be successful in TSC.

Diabetic cardiomyopathy, a severe diabetic complication, impairs heart function, leading to heart failure. Treatment that effectively addresses this condition without causing side effects is urgently needed. Current anti-hyperglycemic therapies are expensive, has side effects and do not effectively prevent cardiac remodeling. Therefore, it is important to explore natural products that may have the potential to reverse cardiac remodeling. That is why the aim of the current study was to determine the left ventricular remodeling potential of the methanolic extract of Artemisia vulgaris in a diabetic cardiomyopathy rat model. Following the initial comprehensive phytochemical evaluation of plant phenolic and flavonoid content, which showed strong anti-hyperglycemic and antioxidant activities, an extract of Artemisia vulgaris was administered in an in vivo experiment. Diabetic cardiomyopathy was induced in Wistar albino rats according to previously described protocols in the literature, and the effect of treatment was checked by serum and histopathological analysis after 45 days. Artemisia vulgaris treatment significantly (p ≤ 0.05) reduced fasting blood glucose (108.5 ± 1.75 mg/dL), glycated hemoglobin (4.03 ± 0.12 %), serum glucose (116.66 ± 3.28 mg/dL), insulin (15.66 ± 0.66 ng/mL), total oxidant status (54.66 ± 3.22 µmol H₂O₂Equiv.L⁻¹), Malondialdehyde (0.20 ± 0.01 mmol/L), total cholesterol (91.16 ± 3.35 mg/dL), triglycerides (130.66 ± 3.15 mg/dL), low-density lipids (36.57 ± 1.02 mg/dL), sodium (140 ± 3.21 mmol/L), calcium (10.44 ± 0.24 mmol/L), creatine kinase MB (1227.5 ± 17.89 IU/L), lactate dehydrogenase (1300 ± 34.64 IU/L), C-reactive protein (30 ± 0.57 pg/mL), tumor necrosis factor-α (58.66 ± 1.76 pg/mL), atrial natriuretic peptide (2.53 ± 0.04 pg/mL), B-type natriuretic peptide (10.66 ± 0.44 pg/mL), aspartate aminotransferase (86.5 ± 4.99 U/L), Alanine Transaminase (55.33 ± 2.90 U/L), urea (25.33 ± 1.15 mg/dL) and creatinine (0.64 ± 0.02 mg/dL) but significantly increased (p ≤ 0.05) total antioxidant capacity (1.73 ± 0.07 mmol Trolox Equil./L), high-density lipids (40 ± 1.59 mg/dL) and potassium (3.82 ± 0.04 mmol/L) levels. ECG and histopathology confirmed the significant improvement in remodeling and the reversal of structural changes in the heart and pancreas. In conclusion, Artemisia vulgaris possesses significant left ventricular remodeling potential in course of diabetes-induced cardiomyopathy.

Diabetes mellitus is a commonly occurring metabolic disorder accompanied by high morbidity and alarming mortality. Besides various available therapies, induction of pancreatic regeneration has emerged as a promising strategy for alleviating the damaging effect of diabetes. Honey, a potent antioxidative and anti-inflammatory agent, has been reported in the literature archive to exhibit favourable results in the regeneration process of several organ systems. The current research work was intended to explore the potential role of manuka honey in pancreatic regeneration in alloxan-induced diabetic rats by accessing the pancreatic histology and levels of relevant transcription factors, including MAFA, PDX-1, INS-1, INS-2, NEUROG3, NKX6-1, and NEUROD. An equal number of rats were allocated to all four experimental groups: normal, negative control, positive control, and treatment group. Diabetes was induced in all groups except normal through a single intraperitoneal dose of alloxan monohydrate. No subsequent treatment was given to the negative control group, while the positive control and treatment groups were supplemented with metformin (150 mg/kg/day) and manuka honey (3 g/kg/day), respectively. Statistical comparison of glucose and insulin levels, oxidative stress indicators, changes in the architecture of pancreatic islets, and expression levels of regeneration-associated transcription factors advocated the potential role of manuka honey in ameliorating the alloxan-induced hyperglycaemia, hyperinsulinemia, oxidative stress, and necrotic changes in islets along with significant upregulation of relevant transcription factors. This suggests to us the auspicious role of antioxidants in honey in pancreatic regeneration and advocates the favourable role of manuka honey in combating diabetes mellitus.