Dental pulp stem cell secretome ameliorates d-galactose induced accelerated aging in rat model.

Advancing age is associated with several diseases and disorders due to multiorgan atrophy. The increasing proportion of elderly humans demands the identification of means to counteract aging and age-associated disorders. There is an increased depletion of stem cells in the aged organs, resulting in their inability to repair the damage and hence organ degeneration. Stem cell therapy has been implicated in counteracting aging and shown promise. However, the use of stem cells encounters several side effects and complications such as handling and storage of the cells for transplantation purpose. Stem cells secretome has proven to be of significant importance in a variety of disorders. In this study, we have shown that secretome derived from dental pulp stem cells (DPSCs) can reverse the age-associated degeneration induced by chronic exposure to d-galactose in a rat model. The secretome was able to increase muscle grip strength and animal activity. Secretome also improved the kidney function and hepatic biochemistry similar to healthy controls as evaluated by renal function test and Fourier-transform infrared spectroscopy. We also showed that secretome reduced the levels of monoamine oxidase and acetylcholinesterase in the brain and liver, indicating aging reversal. Finally, proteomic profiling of DPSCs secretome revealed the presence of 13 proteins which have antiaging functions. Thus, our study provides first proof of concept that DPSCs secretome can render protection against d-galactose induced accelerated aging.

Comparison of the efficacy of chlorhexidine gluconate versus povidone iodine as preoperative skin preparation for the prevention of surgical site infections in clean-contaminated upper abdominal surgeries.

PURPOSE: To compare the efficacy of chlorhexidine-gluconate versus povidone iodine in preoperative skin preparation in the prevention of surgical site infections (SSIs) in clean-contaminated upper abdominal surgeries. METHODS: This was a prospective randomized controlled trial conducted on patients undergoing clean-contaminated upper abdominal surgeries. A total of 351 patients 18-70 years old were randomized into two groups; chlorhexidine and povidone iodine skin preparation before surgery. RESULTS: The incidence of SSIs in the chlorhexidine group was 10.8 %, in comparison to 17.9 % in the povidone iodine group. The odds ratio was 0.6 in favor of chlorhexidine use, but the results were not statistically significant (P = 0.06). In the first postoperative week, SSIs developed in 7 % of patients in the chlorhexidine group and 14.1 % in the povidone iodine group (P = 0.03), and in the second postoperative week, SSIs were present in 4.1 % of the patients in the chlorhexidine group and 4.4 % in the povidone iodine group, which was not statistically significant (P = 0.88). CONCLUSIONS: The incidence of SSIs after clean-contaminated upper abdominal surgeries was lower with the use of chlorhexidine skin preparation than with povidone iodine preparation, although the results were not statistically significant. However, the odds ratio between the two groups favored the use of chlorhexidine over povidone iodine for preventing SSIs.

Disrupting Maternal Behavior and Inducing Cannibalism Due to Valproic Acid: An Unexplored Insight.

Introduction: Valproic acid (VPA) is the most widely used chemical to develop the preclinical model of autism spectrum disorder (ASD). However, in addition to inducing autism, it causes different teratogenic effects like teeth malformation, tail kink, and abnormal body growth in offspring. So far, no study has explored VPA-induced maternal misbehavior, miscarriage, and maternal cannibalism. We aimed to determine the cannibalistic effects of VPA in pregnant female Wistar rats and VPA's influence on causing miscarriage frequency. Methods: Our study was conducted on pregnant Wistar rats. On gestation day (GD) 12.5, they were treated with VPA (600 mg/kg intraperitoneal) dissolved in saline at 250 mg/mL concentration. The observations were mean litter size, mean male/female pups, mean mortality, maternal cannibalism, mean number of pups alive, cannibalism of malformed pups, miscarriage, survival analysis of pups, and odds and risk ratio were calculated for deaths observed in both study (control and VPA-treated) groups. The study was conducted till the weaning period. Results: VPA-exposed pregnant females portrayed significantly decreased litter size (P<0.0001), significantly higher cannibalistic behavior (P=0.0023), and significantly higher cannibalism of malformed pups (P=0.0484) than the control group. VPA had caused complete pregnancy loss (miscarriage) in 5 pregnant females. Moreover, the VPA group's mortality percentage (P=0.0019) was significantly higher than the control group. Conclusion: Overall, VPA has marked teratogenic effects (anatomical and morphological changes in offspring) with maternal behavior disruption, which causes cannibalism in Wistar female rats. The current manuscript findings can aid in investigating the novel mechanisms involved in maternal behavior disruption during the development of the VPA autism model.

An insight into the simulation directed understanding of the mechanism in SARS CoV-2 N-CTD, dimer integrity, and RNA-binding: Identifying potential antiviral inhibitors.

Coronavirus 2019 is a transmissible disease and has caused havoc throughout the world. The present study identifies the novel potential antiviral inhibitors against the nucleocapsid C-terminal domain that aids in RNA-binding and replication. A total of 485,629 compounds were screened, and MD was performed. The trajectory analysis (DCCM & PCA), structural integrity, and degree of compaction depicted the protein-ligand complex stability (PDB-PISA and Rgyr). Results obtained from screening shortlists 13 compounds possessing high Docking score. Further, seven compounds had a permissible RMSD limit (3 Å), with robust RMSF. Post-MD analysis of the top two compounds (204 and 502), DCCM & PCA analysis show a positive atomic displacements correlation among residues of active sites-dimer (Chain A and Chain B) & residual clustering. The ΔGint of RNA-bound (-83.5 kcal/mol) and drug-bound N-CTD-204 (-40.8 kcal/mol) and 502(-39.7 kcal/mol) as compared to Apo (-35.95 kcal/mol) suggests stabilization of protein, with less RNA-binding possibility. The Rgyr values depict the loss of compactness on RNA-binding when compared to the drug-bound N-CTD complex. Further, overlapping the protein complexes (0 ns and 100 ns) display significant changes in RMSD of the protein (204-2.07 Å and 502-1.89 Å) as compared to the Apo (1.72 Å) and RNA-bound form (1.76 Å), suggesting strong interaction for compound 204 as compared to 502. ADMET profiling indicates that these compounds can be used for further experiments (in vitro and pre-clinical). Compound 204 could be a promising candidate for targeting the N-protein-RNA assembly and viral replication.

Congenital malformation and autism spectrum disorder: Insight from a rat model of autism spectrum disorder.

AIMS AND OBJECTIVES: The primary aim was an evaluation of the pattern of gross congenital malformations in a rat model of autism spectrum disorder (ASD) and the secondary aim was characterization of the most common gross malformation observed. MATERIALS AND METHODS: In females, the late pro-oestrous phase was identified by vaginal smear cytology, and then, they were allowed to mate at 1:3 ratio (male: female). Pregnancy was confirmed by the presence of sperm plug in the vagina and presence of sperm in the vaginal smear. In the ASD group, ASD was induced by injecting valproic acid 600 mg/kg (i.p.) to pregnant female rats (n = 18) on day 12.5 (single injection). Only vehicle (normal saline) was given in the control group (n = 12). After delivery, pups were grossly observed for congenital malformations until the time of sacrifice (3 months) and different types of malformations and their frequency were noted and characterized. RESULTS: In the ASD group, congenital malformation was present in 69.9% of the pups, whereas in the control group, it was 0%. Male pups were most commonly affected (90% in males vs. only 39.72% in female pups). The tail deformity was the most common malformation found affecting 61.2% pups in the ASD group. Other malformations observed were dental malformation (3.82%), genital malformation (3.28%) and paw malformation (1.1%). Hind limb paralysis was observed in one pup. The tail anomalies were characterized as per gross appearance and location of the malformation. CONCLUSION: In this well-validated rat model of ASD, congenital malformation was quite common. It seems screening of congenital malformations should be an integral part of the management of ASD, or the case may be vice versa, i.e., in the case of a baby born with a congenital deformity, they should be screened for ASD.