Chlorpyrifos and dimethoate exposure impairs female fertility by deregulating WNT signaling pathway & uterine receptivity.

The study assessed histological, biochemical, oxidative stress, and molecular parameters to evaluate the consequences of Chlorpyrifos and Dimethoate exposure on uterine health in female rats. Despite showing no obvious signs of toxicity apart from minor clinical symptoms in DM-exposed rats, both pesticides caused degenerative changes in uterine tissue. This study demonstrates that pesticides induce inflammatory responses and oxidative stress in rats, by NF-κB activation and altering antioxidant enzyme levels. Besides, CPF and DM exposure disrupted gene expression of HOXA10, HOXA11, and WNT and reduced activation of ß-catenin in the uterus, which is crucial for implantation and reproductive function. These findings suggest that pesticide exposure may impair reproductive health and fertility in females, highlighting potential implications for human health.

Acute and sub-acute Toxicity Profiles of Anchusa strigosa and Zataria Multiflora: Insights from wistar albino rats.

The present study aims to assess the acute and subacute toxicity of the hydro-alcoholic extracts of Anchusa strigosa (leaves) and the aerial parts of Zataria multiflora Boiss in Wistar albino rats. The crude extracts of Anchusa strigosa (leaves) and the aerial parts of Zataria multiflora Boiss were prepared in 70% ethanol. Systematic tests for acute toxicity were performed at varying dosages of 100, 250, and 500 mg/kg, while for subacute toxicity, a dose of 600 mg/kg was orally given to Wistar albino rats. At the end of acute and sub-acute toxicity studies, biochemical parameters, hematological analysis, and histopathological analysis showed no significant difference in the body weight, abnormalities, or organ damage of the rats compared to the untreated rats (control). Also, there were no results of death recorded in rats. These findings indicated that the medium-term oral administration of Anchusa strigosa (leaves) and the aerial parts of Zataria multiflora Boiss after the treatment does not cause toxicity and provides assurance regarding their suitability for potential therapeutic applications in both acute and subacute forms.

Dual cross-linked gellan gum/gelatin-based multifunctional nanocomposite hydrogel scaffold for full-thickness wound healing.

Biological macromolecules are excellent materials for wound dressing owing to their similar structure to the extracellular matrix and adjustable physicochemical properties. This research focuses on fabricating biological macromolecule-based hydrogel with desirable antibacterial, antioxidant, controlled drug release, cytocompatibility, and wound healing properties. Herein, different concentrations of nanoceria (NC) and flurbiprofen (FLU) drug-loaded gellan gum/gelatin (GG/Ge) based dual crosslinked (Ionic and EDC/NHS coupling) hydrogels were engineered. All fabricated hydrogels were hydrophilic, biodegradable, good strength, porous, antioxidant, hemocompatible and cytocompatible. Among all, hydrogel loaded with 500 µg/ml NC (GG/Ge/NC@FLU) exhibited desirable antioxidant, antibacterial (killed Staphylococcus aureus and Escherichia coli within 12 h), hemocompatible, cytocompatible, supports oxidative-stressed L929 cell growth and acted as a controlled release matrix for FLU, following Fickian diffusion, Peppas Sahlin and Korsmeyer-Peppas drug release models. Furthermore, nanocomposite hydrogel (GG/Ge/NC@FLU)-treated wounds of rats on day 14 demonstrated significantly higher collagen synthesis, nearly 100 % wound contractions, and efficiently decreased the expression of TNF-α and IL-1 while increasing the production of IL-10 and TNF-ß3, indicating antiinflammatory activity, and effectively reduced the expression of VEGF gene indicating effective angiogenesis than all other controls. In conclusion, the fabricated multifunctional GG/Ge/NC@FLU nanocomposite hydrogel shows promising potential for effectively treating full-thickness wound healing in a rat model.

Mesenchymal stem cells derived from bone marrow and adipose tissue for repairing acute sciatic nerve injury in a rabbit model.

Peripheral nerve injury is one of the common disabling clinical conditions and around 50% of the cases end up in permanent impairment. Due to the lack of effective treatment options regenerative medicine employing stem cells is being evaluated. The presented study evaluated and compared regeneration potential of mesenchymal stem cells (MSCs) derived from bone marrow (BM) and adipose tissue (AD) in acute rabbit sciatic nerve injury (axonotmesis) model. A total of n = 54 grey giant rabbits were made subject of the study and divided equally into 3 groups: Control, BM-MSCs in Collagen I and AD-MSCs in Collagen I as per the treatment given. Iliac crest BM and omental AD was harvested from the same donor for isolation and culture of MSCs. The repair of sciatic nerve injury was evaluated on days 60 and 90. The clinical and histopathological scores and SEM morphology was better in cell treated groups as compared to the control. Morphology and histological studies revealed injured nerve in different levels of regenerative process. Gene expression was more than double for N-Cadherin in cell treated groups as compared to the control, especially at day 60. Between cell treated groups, BM-MSCs group showed better response as compared to the AD-MSCs, although statistically non-significant (p > 0.05). Incomplete nerve regeneration observed under various diagnostic parameters was in compliance to the incomplete clinical recovery at day 90. It was concluded that MSCs may improve sciatic nerve healing but fall short of complete regeneration at day 90, although BM-MSCs may have an edge over AD-MSCs.

Cryopreserved allogeneic bone marrow mesenchymal stem cells show better osteochondral defect repair potential than adipose tissue mesenchymal stem cells.

Mesenchymal stem cells (MSCs) due to their characteristic properties have a potential to treat osteoarthritis, one of the major growing joint problems. MSCs show differential ex vivo chondrogenic potential on the basis of source that remains to be validated under in vivo environment. This study compared chondrogenic potential of MSCs derived from two common sources, adipose tissue (AD) and bone marrow (BM) under ex vivo and in vivo environments. The randomized placebo controlled osteochondral defect (OCD) study divided n = 72 rabbits equally into Control, AD-MSCs and BM-MSCs groups. Ex vivo chondrogenic induction resulted in an increased aggrecan fold expression in BM-MSCs and AD-MSCs. The former cell type had significantly (p<0.05) higher fold expression as compared to the latter. The cell treated OCDs had significantly reduced gene expression for inflammatory markers (IL-6, IL-8 and TNF-α) as compared to the control. In OCD study, radiography, MRI, gross observation, histopathology and SEM revealed that the cell treated defects were early filled by the tissue that had better surface architecture and matrices as compared to the control. BM-MSCs treated defects had better scores especially for gross and histopathology than the AD-MSCs. Gene expression for osteochondral regulation and cartilaginous matrices was higher in BM-MSCs group while only for matrices including the Col I in AD-MSCs as compared to the control. It was concluded that OCD in the cell treated groups are filled early with mostly a fibrocartilaginous to hyaline tissue. BM-MSCs may have an edge over AD-MSCs in OCD repair.

Cryopreserved allogeneic mesenchymal stem cells enhance wound repair in full thickness skin wound model and cattle clinical teat injuries.

The study was aimed to evaluate and compare the healing potential of mesenchymal stem cells (MSCs) derived from two common sources (iliac crest derived bone marrow and omental fat) in a full thickness skin wound model. Bone marrow derived MSCs clinical efficacy in the repair of cattle teat fistulae (cutaneous and muco-cutaneous wounds) was also evaluated. In a completely randomized placebo controlled experimental full thickness skin wound model, n=36 were randomly divided into three equal groups: groups I, II and III receiving Phosphate buffered saline (PBS), BM-MSCs and adipose tissue MSCs (AD-MSCs), respectively. Grossly early reduction in inflammation and enhanced epithelialization in the cell-treated groups as compared to the control was seen. Microscopy, ultramicroscopy, gene expression analysis and mechanical testing revealed better and early matrix formation with a reduced scar formation and a higher tensile strength in the cell-treated groups as compared to the control. An overall comparable healing in the cell treated groups was observed, although BM-MSCs had led to the better matrix formation tending to scarless healing while the AD-MSCs had led to the early wound closure with a good tissue strength. In the case controlled bovine clinical teat injuries study (n=17) repaired surgically, BM-MSCs (n=13) or PBS (n=4) was injected locally. In surgico-MSCs treated cases, 84.6% non-recurrence rate was observed as compared to the 50% seen in the control. It was concluded that MSCs irrespective of the donor tissue have potential to improve healing of full thickness cutaneous wounds and/ fistulae.

Immune and Oxidative Response against Sonicated Antigen of Mycoplasma capricolum subspecies capripneumonia-A Causative Agent of Contagious Caprine Pleuropneumonia.

Vaccines are vital for prevention and control of mycoplasma diseases. The exploration of a vaccine candidate for the development of a vaccine is imperative. The present study envisages the evaluation of immune and oxidative response against an adjuvanted, sonicated antigen of Mycoplasma capricolum subsp. capripneumonia in male Angora rabbits (1 year old, 2 kg) divided in four groups, each having six animals. Group 1 was the healthy control and received 1 mL PBS via subcutaneous route. Group 2 was administered 1 mL of saponin-adjuvanted and -sonicated antigen, Group 3 was given 1 mL of montanide ISA 50-adjuvanted and-sonicated antigen, and Group 4 was given 1 mL of standard vaccine via subcutaneous route. Animals were evaluated for cellular and humoral immune response and oxidative parameters at 0, 7, 14, 21, and 28 days of the study. Total leukocytic, neutrophilic, and basophilic counts showed a significant (p < 0.05) increase in vaccinated groups compared to the healthy group on most of the intervals. TNF-α levels were significantly (p < 0.05) higher in the Group 2 than the Group 1 at all the time intervals and more comparable to Group 4 than Group 3. IL-10 levels were significantly (p < 0.05) higher in vaccinated groups compared to the healthy group on days 14, 21, and 28, but were lower in Group 3 than in Group 2 and Group 4. More hypersensitivity as inflammation and histopathological cellular infiltration in the ear was produced in Group 2 and Group 4 than in Group 3. IgG levels were significantly (p < 0.05) higher in Group 2 and Group 4 than in Group 3 on days 14 and 21. Antibody titers were comparatively higher in Group 4, followed by Group 2 and 3, than Group 1. Significantly (p < 0.05) higher oxidant and lower antioxidant values were noted in Group 2 and 4 compared to Group 3 and Group 1 on most of the intervals. The TLC and antibody titer showed increasing trend throughout the trial, whereas TNF-α, IgG, L, M and E started decreasing from day 14, and IL-10, N and B started decreasing from day 21. This study concludes that the saponin-adjuvanted and-sonicated antigen induces comparatively higher immune response than montanide but is associated with oxidative and inflammatory reactions.

Poor Sleep in Community-Dwelling Polysubstance Users: Association With Khat Dependence, Metacognition, and Socio-Demographic Factors.

Purpose: Poor sleep and cognitive deficits are often associated with increased drug use. However, no study has addressed the relationship between poor sleep, substance dependence, and metacognitive deficit in polysubstance users. Methods: This was a cross-sectional study with a simple random sampling involving community-dwelling polysubstance users (n = 326, age = 18-43 years) in Mizan, Ethiopia. Participants completed a brief sleep questionnaire, severity of dependence on khat (SDS-Khat), a brief meta-cognition questionnaire, and a socio-demographic survey. Results: Majority (56.4%) of the polysubstance users had sleep disturbance. Chronic health conditions [adjusted odds ratio (AOR) = 2.52, 95% confidence interval (CI) 1.31-4.85], chronic conditions in the family (AOR = 2.69, 95% CI 1.40-5.20), illiterate-primary level of educational status (AOR = 2.40, 95% CI 1.30-4.04), higher SDS-Khat score (AOR = 1.39, 95% CI 1.13-1.72), and lower meta-cognition score (AOR = 0.90, 95% CI 0.84-0.97) predicted poor sleep in the polysubstance users. Moreover, low metacognition score and high SDS score also predicted additional sleep disturbances like chronic sleep insufficiency, lethargy and restlessness after nighttime sleep, socio-occupational dysfunctions, and daytime disturbances in polysubstance users. Conclusion: Poor sleep, severe khat dependence, and metacognitive deficits are common in community polysubstance users. Moreover, poor sleep is associated with higher khat dependence, lower metacognitive ability, lower educational status, and the presence of chronic conditions in polysubstance users or their families.

Psychometric properties of the Insomnia Severity Index in Ethiopian adults with substance use problems.

This study investigated the psychometric properties of the Insomnia Severity Index (ISI) in substance-using Ethiopian adults. A simple random sampling of houses and a purposive sampling selection was performed in Mizan city, Ethiopia (n = 406). Participants completed the ISI and a meta-cognition questionnaire and sociodemographic information. IBM SPSS software with Amos was used for data analysis. There was no major ceiling or floor effect in the ISI scores. The internal consistency (Cronbach's alpha = 0.68 and 0.78) and internal homogeneity (moderate to strong item-total ISI score correlations; r ≥ 0.47) were adequate. All of the ISI (item as well as total) scores correlated with the meta-cognition total scores (r = 0.16-0.44; p < .01). The exploratory factor analysis results were heterogeneous. However, the confirmatory factor analysis favored a 2-factor model. The ISI has good psychometric validity among Ethiopian adults with substance use.

Gross and histopathological alterations associated with cystic echinococcosis in small ruminants.

Hydatidosis, an important parasitic zoonoses is a major public health as well as economic concern throughout the world. A total of 2100, sheep (2052) and goats (48), slaughtered or spontaneously dead, from various areas of Kashmir valley were screened for the presence of hydatidosis. Out of 2100 cases, 85 were positive for hydatidosis. The frequently infected organs were lungs and liver. The liver was observed to be the most frequently infected organ with relative prevalence of 61.17% followed by lungs (38.82%). The pulmonary cysts were more fertile (55%) compared to hepatic cysts (45%). Histopathologicallly, the cyst wall consisted of the inner germinal, middle lamellated/laminated, and outer fibrous layer. Inflammatory reaction around the cyst was variable and was characterized by an inner zone of loosely arranged fibroblasts infiltrated with mononuclear cells, followed by densely arranged fibroblasts along with mononuclear cells; and an outer layer of fibrous connective tissue. Fibroplasia and calcification were noted at places. In liver besides the cellular reaction against the expanding cyst, hepatocellular degeneration and cirrhosis were observed, the severity of which was inversely related to the distance from the cyst. The structural details of the protoscolices were clearly discernable.