Autism is associated with gastrointestinal dysfunction and gut microbiota dysbiosis, including an overall increase in Clostridium. Modulation of the gut microbiota is suggested to improve autistic symptoms. In this study, we explored the implementation of two different interventions that target the microbiota in a rodent model of autism and their effects on social behavior: the levels of different fecal Clostridium spp., and hippocampal transcript levels. Autism was induced in young Sprague Dawley male rats using oral gavage of propionic acid (PPA) for three days, while controls received saline. PPA-treated animals were divided to receive either saline, fecal transplant from healthy donor rats, or Bifidobacterium for 22 days, while controls continued to receive saline. We found that PPA attenuated social interaction in animals, which was rescued by the two interventions. PPA-treated animals had a significantly increased abundance of fecal C. perfringens with a concomitant decrease in Clostridium cluster IV, and exhibited high hippocampal Bdnf expression compared to controls. Fecal microbiota transplantation or Bifidobacterium treatment restored the balance of fecal Clostridium spp. and normalized the level of Bdnf expression. These findings highlight the involvement of the gut–brain axis in the etiology of autism and propose possible interventions in a preclinical model of autism.

In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumorigenic and triple-negative breast cancer cell line, KAIMRC2. This cell line is derived from a Saudi Arabian female breast cancer patient with invasive ductal carcinoma. Immunocytochemistry showed a significant ratio of the KAIMRC2 cells’ expressing key breast epithelial and cancer stem cells (CSCs) markers, including CD47, CD133, CD49f, CD44, and ALDH-1A1. Gene and protein expression analysis showed overexpression of ABC transporter and AKT-PI3Kinase as well as JAK/STAT signaling pathways. In contrast, the absence of the tumor suppressor genes p53 and p73 may explain their high proliferative index. The mice model also confirmed the tumorigenic potential of the KAIMRC2 cell line, and drug tolerance studies revealed few very potent candidates. Our results confirmed an aggressive phenotype with metastatic potential and cancer stem cell-like characteristics of the KAIMR2 cell line. Furthermore, we have also presented potent small molecule inhibitors, especially Ryuvidine, that can be further developed, alone or in synergy with other potent inhibitors, to target multiple cancer-related pathways.

To investigate the effect of the therapeutic treatment of the immunopeptide, peptide inhibitor of trans-endothelial migration (PEPITEM) on the severity of disease in a mouse model of experimental autoimmune encephalomyelitis (EAE) as a model for human multiple sclerosis (MS), a series of experiments were conducted. Using C57BL/6 female mice, we dosed the PEPITEM in the EAE model via IP after observing the first sign of inflammation. The disease was induced using MOG35-55 and complete Freund’s adjuvants augmented with pertussis toxin. The EAE score was recorded daily until the end of the experiment (21 days). The histological and immunohistochemistry analysis was conducted on the spinal cord sections. A Western blot analysis was performed to measure the protein concentration of MBP, MAP-2, and N-Cadherin, and ELISA kits were used to measure IL-17 and FOXP3 in the serum and spinal cord lysate. The therapeutic treatment with PEPITEM reduced the CNS infiltration of T cells, and decreased levels of the protein concertations of MBP, MAP-2, and N-Cadherin were observed, in addition to reduced concertations of IL-17 and FOXP3. Using PEPITEM alleviated the severity of the symptoms in the EAE model. Our study revealed the potential of PEPITEM to control inflammation in MS patients and to reduce the harmful effects of synthetic drugs.

Background Vitamin D deficiency is linked to cardiovascular and respiratory instability, particularly during hypoxic stress, such as in obstructive sleep apnea (OSA). However, the mechanisms connecting vitamin D status to hemodynamic and cardiorespiratory responses in hypoxia remain unclear. Objective This study aimed to assess the impact of vitamin D deficiency on hemodynamic (mean arterial pressure and heart rate) and cardiorespiratory (respiratory rate and peripheral oxygen saturation) stability in an OSA experimental model, along with the effects of dose-dependent vitamin D supplementation. Methods Fifty-six adult male Sprague Dawley rats were divided into seven groups: control, vitamin D-deficient, vitamin D-deficient with severe intermittent hypoxia (IH) and supplementation subgroups exposed to varying levels of IH. Vitamin D deficiency was induced through a diet lacking vitamin D for three weeks, followed by oral supplementation at two doses (25 µg/kg/day and 37.5 µg/kg/day) for two weeks. Intermittent hypoxia was simulated for 14 days, and serum 25-hydroxyvitamin D (25OHD) levels were measured using Elisa. Hemodynamic and cardiorespiratory parameters were recorded, and heart, aorta tissue were analyzed. Results Vitamin D-deficient groups exhibited significantly lower serum 25OHD levels and showed increased mean arterial pressure, heart and respiratory rates, and reduced oxygen saturation under hypoxia. High-dose supplementation improved 25OHD levels and improved physiological measures, particularly in moderate hypoxia subgroups (p = 0.001). Conclusion Vitamin D deficiency combined with intermittent hypoxia increased mean arterial pressure, heart rate, and respiratory rate, reduced oxygen saturation, and worsened cardiovascular histology. Vitamin D supplementation improved these changes, especially at higher dose, and protected cardiovascular structures. Graphical Abstract Vitamin D deficiency combined with intermittent hypoxia induces hemodynamic and respiratory instability and causes cardiovascular tissue alterations. Vitamin D supplementation improves physiological parameters, with greater effects at higher dose, and preserves heart and aortic structure in an obstructive sleep apnea rat model.

Background/Objectives: Children with autism spectrum disorder (ASD) frequently experience poor compliance with oral medication due to bitterness, unpleasant taste, and unsuitable dosage forms such as large tablets or capsules. Risperidone, a widely prescribed antipsychotic for managing ASD symptoms, is particularly challenging in this regard. The present study aimed to develop a novel sucrose-based microfiber drug delivery system to improve the palatability, acceptance, and bioavailability of risperidone in pediatric patients with ASD. Methods: Risperidone was incorporated into sucrose microfibers using centrifugal spinning technology. Fiber morphology was characterized by scanning electron microscopy (SEM). Drug loading (DL), encapsulation efficiency (EE%), and disintegration time were measured. In vitro drug release and cytotoxicity assays were performed using human foreskin fibroblast cells (HFF-1). An in vivo palatability and preference study was conducted in male BALB/c mice to evaluate the acceptability of the formulation compared with a commercial risperidone oral solution. Results: SEM analysis revealed smooth, bead-free, non-porous fibers with uniform morphology and size distribution. The formulation showed a rapid disintegration time of ~3 s, DL of 30 ± 5 µg/mg, and EE% of 60 ± 10%. Approximately 50% of risperidone was released within 15 min. Cytotoxicity testing confirmed that concentrations ≤ 125 µg/mL maintained high cell metabolic activity, indicating biocompatibility. In vivo, the microfiber solution demonstrated a strong preference (93%) compared with the commercial oral solution (30%). Conclusions: Risperidone-loaded sucrose microfibers represent a promising fast-dissolving oral delivery system for children with ASD. This child-friendly formulation improves palatability and compliance while maintaining safety and drug release performance.

Background: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress and evaluates whether Galectin-3 (Gal-3) inhibition modulates surfactant homeostasis. Methods: Forty adult male Sprague-Dawley rats (8 per group) were randomized to Control (normoxia), Moderate IH (MIH; 15–30 events/hour), Severe IH (SIH; 30–60 events/hour), MIH + Gal-3 inhibitor (Modified Citrus Pectin, 800 mg/kg/day), or SIH + Gal-3 inhibitor. IH exposure lasted 8 h/day for 10 days. Outcomes included circulating SP-D, Surfactant Protein B (SP-B), inflammatory markers, physiological parameters, and histopathological lung injury scores assessed via American Thoracic Society guidelines. Results: SP-D levels showed numerical reductions with increasing IH severity (Control: 1969.07 pg/mL [IQR: 262.15]; SIH: 1404.30 pg/mL [IQR: 351.88]), representing a 28.6% decrease. However, between-group variability resulted in non-significant omnibus testing (Kruskal–Wallis p = 0.187). Gal-3 inhibition elevated SP-D levels, particularly in severe IH (2133.95 pg/mL [IQR: 1240.70]), though high inter-individual variability was observed (CV = 58.1%). SP-B showed significant suppression under moderate IH (p = 0.019) with restoration by treatment. Exploratory correlation analysis revealed moderate positive associations between SP-D and heart rate (r = 0.587) and respiratory rate (r = 0.419) in severe IH, though these did not reach statistical significance (p = 0.126 and p = 0.301, respectively). Histologically, severe IH induced diffuse alveolar damage (total lung score: 19.67 ± 0.82). Gal-3 inhibition produced context-dependent effects: protective in severe IH but paradoxically exacerbating inflammation under moderate IH (29.20 ± 4.64 vs. 20.00 ± 4.34; p < 0.05). Gal-3 inhibition significantly attenuated cardiac injury (injury score: 0.00 ± 0.00 vs. 7.17 ± 0.75 in severe IH; p < 0.001, η² = 0.859). Conclusions: SP-D demonstrates severity-associated alterations consistent with alveolar epithelial stress during IH, though high variability limits definitive biomarker validation in this sample. Gal-3 inhibition modulates surfactant homeostasis and attenuates cardiopulmonary injury in a context-dependent manner. These findings support further investigation into SP-D as a component of multimodal severity stratification in OSA and highlight Gal-3 inhibition as a context-dependent anti-inflammatory strategy, pending validation in larger cohorts with tissue-level confirmation.