The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain.

Methamphetamine, a highly addictive central nervous system (CNS) stimulant, is used worldwide as an anorexiant and attention enhancer. Methamphetamine use during pregnancy, even at therapeutic doses, may harm fetal development. Here, we examined whether exposure to methamphetamine affects the morphogenesis and diversity of ventral midbrain dopaminergic neurons (VMDNs). The effects of methamphetamine on morphogenesis, viability, the release of mediator chemicals (such as ATP), and the expression of genes involved in neurogenesis were evaluated using VMDNs isolated from the embryos of timed-mated mice on embryonic day 12.5. We demonstrated that methamphetamine (10 µM; equivalent to its therapeutic dose) did not affect the viability and morphogenesis of VMDNs, but it reduced the ATP release negligibly. It significantly downregulated Lmx1a, En1, Pitx3, Th, Chl1, Dat, and Drd1 but did not affect Nurr1 or Bdnf expression. Our results illustrate that methamphetamine could impair VMDN differentiation by altering the expression of important neurogenesis-related genes. Overall, this study suggests that methamphetamine use may impair VMDNs in the fetus if taken during pregnancy. Therefore, it is essential to exercise strict caution for its use in expectant mothers.

Evaluation of efficacy of non-resorbable membranes compared to resorbable membranes in patients undergoing guided bone regeneration.

Background: Replacement of missing teeth in patients with prolonged edentulism poses a challenge for clinicians. An extended period of edentulism results in severe atrophy of alveolar ridges rendering them unsatisfactory for rehabilitation using an implant-supported prosthesis. To overcome this difficulty, Guided Bone Regeneration (GBR) was introduced and constructed upon the principles of Guided Tissue Regeneration (GTR) procedures. Evidence suggests that GBR has proven to be a predictable treatment modality for treating vertical and horizontal ridge deficiencies. Objective: The present systematic review aimed to evaluate the efficacy of non-resorbable (N-RES) membranes compared to resorbable (RES) membranes in patients undergoing GBR. Methods: An electronic search of three databases, including PubMed, Web of Science, and Scopus, was conducted for articles published until March 2022. A supplementary manual search of references from these articles was performed to include any articles that may have been overlooked in the electronic search. Articles that evaluated the efficacy of RES membranes and N-RES membranes in GBR were included. Case reports, case series, commentaries, letters to the editor, narrative or systematic reviews were excluded. Articles in languages other than English were also excluded. The articles were assessed against risk of bias 2 tool for Randomized Control Trials (RCTs) and ROBINS-I tool for Non-Randomized Clinical Trials (N-RCTs). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment was followed based on the Cochrane Handbook for quality assessment. A summary of findings table was used to present the results. Results: One hundred and fifty one articles were identified in an electronic search. Eight articles met the inclusion criteria and were included in the present systematic review. The studies were conducted on partially or completely edentulous patients with alveolar ridge deficiencies undergoing vertical or horizontal bone for subsequent implant placement. The majority of the studies reported similar results for bone gain in both RES and N-RES membrane groups. Conclusion: The available evidence suggests that RES and N-RES membranes are equally effective in GBR. However, the evidence must be interpreted with caution due to its 'low quality' GRADE assessment. Clinical implications: Further research focusing on human clinical trials with well-matched subjects with homogeneity in the type and method of GBR and method of assessment of new bone formation will derive conclusive results on the efficacy of RES and N-RES membranes in achieving new bone formation.

Apigenin protects from hepatorenal damage caused by lead acetate in rats.

Exposure to lead (Pb) is associated with serious health problems including hepatorenal toxicity. Apigenin is a natural-sourced flavonoid with promising antioxidant and anti-inflammatory effects. In this research, we investigated the potential protective role of apigenin against lead acetate (PbAc)-induced hepatorenal damage. Thus, this experiment studied the exposure of male Wistar Albino rats to apigenin and/or PbAc and their effects in comparison to the control rats. Apigenin administration decreased the levels of Pb and prevented the histopathological deformations in liver and kidney tissues following PbAc exposure. This was confirmed by the normalized levels of liver and kidney function markers. Additionally, apigenin inhibited significantly oxidative reactions through upregulating Nrf2 and HO-1, and activating their downstreamed antioxidants accompanied by a marked depletion of pro-oxidants. Moreover, apigenin decreased the elevated pro-inflammatory cytokines and inhibited cell loss in liver and kidney tissues in response to PbAc intoxication in both tissues. The obtained results demonstrated that apigenin could be used to attenuate the molecular, biochemical, and histological alterations associated with Pb exposure due to its potent antioxidant, anti-inflammatory, and antiapoptotic effects.

Role of Toothbrushes as Gene Expression Profiling Tool for Oral Cancer Screening in Tobacco and Alcohol Users.

AIM: The use of toothbrushes was investigated as a potential RNA source and gene expression profiling tool for oral cancer screening in tobacco and alcohol users. METHODOLOGY: A total of 20 subjects were selected on the basis of inclusion and exclusion criteria. They were divided into two groups: group I-healthy controls (n = 6); group II-individuals who consume tobacco and alcohol (n = 14). After the volunteers brushed their teeth using a soft-bristle toothbrush with ~0.5 gm of toothpaste, the toothbrushes were collected, and the gene expression of BAX, BCL2, CDK4, CKDN2A, GNB3, and TCF7L2 was assessed. RESULTS: The gene expression of BAX decreased significantly in alcoholics and smokers (0.13867 ± 0.12014), while the gene expression of BCL2 increased in alcoholics and smokers (1.91001 ± 0.90425) in comparison with healthy controls (p = 0.0054 and p = 0.0055). Although there was increased expression of CDK4, CKDN2A, and TCF7L2 and decreased expression of GNB3 in smokers and alcoholics, the results were not significant. CONCLUSIONS: A toothbrush is a good source of RNA, and gene expression analysis can be performed using the genetic material retrieved from toothbrushes, which can aid in the early diagnosis of oral squamous cell carcinoma among tobacco and alcohol users. Further studies with a larger sample size and different durations of toothbrush use should be conducted to explore the role of toothbrushes as a noninvasive tool for disease diagnosis.

Assessing the therapeutic potential of agomelatine, ramelteon, and melatonin against SARS-CoV-2.

BACKGROUND: The SARS-Cov-2(severe acute respiratory syndrome coronavirus 2) infection affecting human populations worldwide is now a very concerning issue considering the morbidity and mortality rates. Despite several measures followed by the medical fraternity and general public, there is no resolution. Therapeutic measures to tackle the infection have been based on researching new designer drug molecules that could prevent viral entry into the human host. Melatonin has been tried as an adjuvant in the management of COVID 19(coronavirus disease) illness but its specific antiviral role has not been investigated. Objectives: The objectives of the present study were to conduct an in-silico analysis to investigate if melatonin and related drugs namely ramelteon and agomelatine could be used as antiviral agents in SARS-CoV-2 infection based on their binding to the SARS-CoV-2 receptor binding site (RBD) and Angiotensin-converting enzyme 2 (ACE 2). METHODS: For docking studies (Pdb Id 1M0J), the SARS-CoV-2 spike protein receptor-binding domain (RBD) crystal structure which was ACE2 cell receptor bounded was employed. From the PubChem database, the three-dimensional configuration of the ligands melatonin, ramelteon, and agomelatine was retrieved, and conceptual density functional theory (CDFT) was performed to determine molecular descriptors. Charges were added and optimized with the universal force field to prepare the ligands for the process of docking. For facilitation of readability by the AutoDock software conversion to PDBQT(Protein Data Bank, Partial Charge (Q), & Atom Type (T)) format was performed. AutoDock version 4.2.6 docking program and AutoDock Tools (ADT) version 1.5.6 were used for molecular docking. Desmond, a Package of Schrödinger LLC was used to simulate molecular dynamics for hundred nanoseconds using. RESULTS: Data from the present study reveal that melatonin, ramelteon, and agomelatine demonstrate significant binding with SARS-CoV-2 RBD and ACE 2 demonstrating the fact that they can strongly prevent viral entry into the host cells through dual binding effects. However, Ramelteon was found to be the most superior amongst the 3 drugs analyzed in its antiviral properties against SARS-CoV-2. CONCLUSION: Results advocate further research in exploring the potential therapeutic applications of melatonin, ramelteon, and agomelatine for the management of SARS-CoV-2 infection.