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Background:Synucleinopathies are disorders characterized by the abnormal accumulation of α-synuclein (aSyn). Synaptic compromise is observed in synucleinopathies parallel to aSyn aggregation and is accompanied by transcript deregulation.Objective:We sought to identify microRNAs associated with synaptic processes that may contribute to synaptic dysfunction and degeneration in synucleinopathies.Methods:We performed small RNA-sequencing of midbrain from 6-month-old transgenic mice expressing A30P mutant aSyn, followed by comparative expression analysis. We then used real-time quantitative polymerase chain reaction (qPCR) for validation. Functional analysis was performed in primary neurons by biochemical assays and imaging.Results:We found several deregulated biological processes linked to the synapse. miR-101a-3p was validated as a synaptic miRNA upregulated in aSyn Tg mice and in the cortex of dementia with Lewy bodies patients. Mice and primary cultured neurons overexpressing miR-101a-3p showed downregulation of postsynaptic proteins GABA Ab2 and SAPAP3 and altered dendritic morphology resembling synaptic plasticity impairments and/or synaptic damage. Interestingly, primary cultured neuron exposure to recombinant wild-type aSyn species efficiently increased miR-101a-3p levels. Finally, a dynamic role of miR-101a-3p in synapse plasticity was shown by identifying downregulation of miR-101a-3p in a condition of enhanced synaptic plasticity modelled in Wt animals housed in enriched environment.Conclusion:To conclude, we correlated pathologic aSyn with high levels of miR-101a-3p and a novel dynamic role of the miRNA in synaptic plasticity.

Introduction: Acne is a common cutaneous disease affecting the pilosebaceous apparatus, in which there is hyperkeratinization, excessive sebum production, follicular colonization with Propionibacteriun acnes & inflammation. It manifests as comedones, papules, pustules, nodules & cysts on the face, neck, and trunk. Epidemiologic studies indicate acne affects approximately 9.4% of the global population, ranking it as the eighth most prevalent disease worldwide. It is a common skin condition of the face and trunk that negatively impacts the quality of life. Objectives: We evaluated the efficacy of oral doxycycline in combination with topical trifarotene in the treatment of moderate to severe acne vulgaris. Methods: This was an interventional study for 12-week duration to see the treatment outcome in moderate & severe acne patients. This study was carried out at the Dept. of Dermatology & Venereology, Enam medical college Hospital, Savar, Dhaka, Bangladesh from January 2022 to September 2022. We evaluated a new therapeutic regimen: Doxycycline 100 mg (Oral) once daily during dinner with food and enough water,21 days / month, for three consecutive months along with topical Trifarotene 0.005%w/w once daily at night after proper cleansing for the same duration. Acne severity was graded using Investigator Global Acne Assessment Scale (IGAS). Results: A total of 96 patients with moderate to severe acne were treated & among them 85 completed this study. Out of these 85, 15 are males & 70 are females. There was a marked improvement in IGAS with marked reduction in the number of inflammatory and non-inflammatory lesions between the beginning of the study and through follow up visits. Clinical response to Doxycycline Plus Trifarotene was excellent in 15%, good in 68%, moderate in 14% and mild in 3% and satisfaction to treatment was 22% very satisfied, 60% satisfied and 17% somewhat satisfied. Side effects were low and only 2.1% of cases had mild irritation. ........

Introduction: Gastric polyps are abnormal luminal growths projecting above the plane of the mucosal surface of the stomach. These may be malignant or non-malignant. Hyperplastic polyps are more frequent than other gastric polyps, where H. pylori infections are commonly seen. Most hyperplastic polyps disappear or regress after H. pylori eradication. In Bangladesh, the prevalence of H. pylori in the adult is >92%. The test and treat strategy is not well practised in our country. So, estimation of H. Pylori infection related to gastric polyp is necessary. Aim of the Study: The study aims to investigate the endoscopic and histopathological pattern of gastric polyps with Helicobacter Pylori infection. Methods: This cross-sectional study was carried out in the department of Gastroenterology, BSMMU. In total 75 patients, 24 male and 51 female were included in this study. Information about the clinical profile, endoscopic findings, rapid urease test and histopathological findings were collected. Data were collected using a pre-designed data collection sheet. The collected data were analyzed by computer with the help of SPSS version 23. Statistical analysis was done by using an appropriate statistical tool like the Chi-square test, Student’s t-test, and regression test. Statistical significance will be defined as p

The ongoing coronavirus disease 2019 (COVID-19) pandemic has spurred rapid development of vaccines as part of the public health response. However, the general strategy used to construct recombinant trimeric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) proteins in mammalian cells is not completely adaptive to molecular farming. Therefore, we generated several constructs of recombinant S proteins for high expression in Nicotiana benthamiana. Intramuscular injection of N. benthamiana-expressed S

Background: The ideal portion of dexmedetomidine for shivering control with the most un-hemodynamic disturbances is still under research. Postanesthetic shivering (PAS) is an unsavory and possibly serious difficulty. Not very many investigations have been finished in regards to the ideal compelling portion of dexmedetomidine for the counteraction of postspinal anesthesia (SA) shivering. Accordingly, we expected to look at and assess three distinct portions of intravenous dexmedetomidine and to explore the ideal portion of dexmedetomidine that successfully forestalls shivering in patients going through transurethral resection of the prostate (TURP). Materials and Methods: In this randomized, twofold visually impaired, planned study, 135 patients of the American Society of Anesthesiologists I and II booked for elective TURP under SA were selected. Patients were haphazardly apportioned into one of the three gatherings getting dexmedetomidine: Group P: 0.5 μg/kg, Group Q: 0.75 μg/kg, and Group R: 1.0 μg/kg. The essential result of the review was intraoperative rate of shivering. The optional results, like hemodynamic boundaries. Results: Shivering score of various gatherings uncovered measurably huge lower occurrence and seriousness of shivering in Group Q and Group R when contrasted with Group P(P = 0.0395). Occurrences of sickne, bradycardia, and hypotension were more in Group R when contrasted with Group P and Group Q. Axillary temperature and sedation scores were equivalent among various gatherings (P > 0.05). Conclusion: Dexmedetomidine in the dose of 0.75 μg/kg furnishes sufficient antishivering impact with added advantage of sedation and less hemodynamic disturbance.

Molecules with at least one unpaired electron in their outermost shell are known as free radicals. Free radical molecules are produced either within our bodies or by external sources such as ozone, cigarette smoking, X-rays, industrial chemicals, and air pollution. Disruption of normal cellular homeostasis by redox signaling may result in cardiovascular, neurodegenerative diseases and cancer. Although ROS (reactive oxygen species) are formed in the GI tract, little is known about how they contribute to pathophysiology and disease etiology. When reactive oxygen species and antioxidants are in imbalance in our bodies, they can cause cell structure damage, neurodegenerative diseases, diabetes, hypercholesterolemia, atherosclerosis, cancer, cardiovascular diseases, metabolic disorders, and other obesity-related disorders, as well as protein misfolding, mitochondrial dysfunction, glial cell activation, and subsequent cellular apoptosis. Neuron cells are gradually destroyed in neurodegenerative diseases. The production of inappropriately aggregated proteins is strongly linked to oxidative stress. This review’s goal is to provide as much information as possible about the numerous neurodegenerative illnesses linked to oxidative stress. The possibilities of multimodal and neuroprotective therapy in human illness, using already accessible medications and demonstrating neuroprotective promise in animal models, are highlighted. Neuroprotection and neurolongevity may improve from the use of bioactive substances from medicinal herbs like Allium stadium, Celastrus paniculatus, and Centella asiatica. Many neuroprotective drugs’ possible role has been addressed. Preventing neuroinflammation has been demonstrated in several animal models.

The emergence of various diseases during the COVID-19 pandemic made health workers more attentive, and one of the new pathogens is the black fungus (mucormycosis). As a result, millions of lives have already been lost. As a result of the mutation, the virus is constantly changing its traits, including the rate of disease transmission, virulence, pathogenesis, and clinical signs. A recent analysis revealed that some COVID-19 patients were also coinfected with a fungal disease called mucormycosis (black fungus). India has already categorized the COVID-19 patient black fungus outbreak as an epidemic. Only a few reports are observed in other countries. The immune system is weakened by COVID-19 medication, rendering it more prone to illnesses like black fungus (mucormycosis). COVID-19, which is caused by a B.1.617 strain of the SARS-CoV-2 virus, has been circulating in India since April 2021. Mucormycosis is a rare fungal infection induced by exposure to a fungus called mucormycete. The most typically implicated genera are Mucor rhyzuprhizopusdia and Cunninghamella. Mucormycosis is also known as zygomycosis. The main causes of infection are soil, dumping sites, ancient building walls, and other sources of infection (reservoir words "mucormycosis" and "zygomycosis" are occasionally interchanged). Zygomycota, on the other hand, has been identified as polyphyletic and is not currently included in fungal classification systems; also, zygomycosis includes Entomophthorales, but mucormycosis does not. This current review will be focused on the etiology and virulence factors of COVID-19/mucormycosis coinfections in COVID-19-associated mucormycosis patients, as well as their prevalence, diagnosis, and treatment.

Bronchial carcinoma is currently the most common cause of cancer-related mortality worldwide. The increasing incidence could be due to increased smoking habits, change in lifestyles, increased environmental pollution, and the availability of different modalities to detect lung cancer. Fibreoptic bronchoscopy was introduced in 1968 to evaluate bronchopulmonary lesions. Since then, various methods for obtaining good specimens have become available apart from sputum. A higher positive rate was obtained from specimens collected by fiberoptic bronchoscope. We aimed to assess the sensitivity and specificity of brushings compared with the biopsy of lung lesions. The study was done on 100 patients, of which bronchial brush cytology was done in all 100 cases, and endobronchial biopsy was carried out in 20 cases. This study showed sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of brushing to be 87.5%, 75%, 85%, 93.13%, and 60%, respectively. TAJ 2022; 35: No-1: 107-115

The present study deals with the advanced in-silico analyses of several Apigenin derivatives to explore human papillomavirus-associated cervical cancer and DNA polymerase theta inhibitor properties by molecular docking, molecular dynamics, QSAR, drug-likeness, PCA, a dynamic cross-correlation matrix and quantum calculation properties. Initially, the literature study revealed that Apigenin has potent antimicrobial and anticancer properties. So, their potential derivatives are picked up to determine human papillomavirus-associated cervical cancer and DNA polymerase theta inhibitor properties. The findings were streamlined by exposing the in silico molecular docking, highlighting that all the Apigenin derivatives exhibit prospective interactions of energy binding with targeted proteins. The Apigenin 4'-O-Rhamnoside and Apigenin-4'-Alpha-L-Rhamnoside were more potent against HPV45 oncoprotein E7 (PDB ID 2EWL), where the Apigenin and Apigenin 5-O-Beta-D-Glucopyranoside showed significant binding energy against L1 protein of human. Similarly, the binding affinity range is achieved from -7.5 kcal/mol to -8.8 kcal/mol against DNA polymerase theta, representing that Apigenin derivatives should inhibit the DNA polymerase theta (PDB ID 8E23). Then, this finding was confirmed by molecular dynamic simulation at 100ns and analysis of different parameters such as RMSD, RMSF, SASA, H-bond, and RoG profiles and it is found that our selected compounds were found to be potentially stable. When stability testing is passed, the ADMET, pharmacokinetics, and drug-likeness properties are screened and fulfilled by all the criteria. Moreover, QSAR, PCA, Dynamic cross-correlation matrix, and quantum calculation were also conducted and the outcome was satisfied. As this study was carried out using in silico computational approaches and obtained outstanding results. So, to validate these results, further wet-lab experiments might be carried out under in vivo and in vitro conditions.

Schizophrenia is a psychiatric disorder that is still not readily treatable. Pharmaceutical advances in the treatment of schizophrenia have mainly focused on the protein coding part of the human genome. However, the vast majority of the human transcriptome consists of non-coding RNAs. MicroRNAs are small non-coding RNAs that control the transcriptome at the systems level. In the present study we analyzed the microRNAome in blood and postmortem brains of controls and schizophrenia patients and found that miR-99b-5p was downregulated in both the prefrontal cortex and blood of patients. At the mechanistic level we show that inhibition of miR-99b-5p leads to schizophrenia-like phenotypes in mice and induced inflammatory processes in microglia linked to synaptic pruning. The miR-99b-5p-mediated inflammatory response in microglia depended onZ-DNA binding protein 1(Zbp1) which we identified as a novel miR-99b-5p target. Antisense oligos (ASOs) againstZbp1ameliorated the pathological phenotypes caused by miR-99b-5p inhibition. In conclusion, we report a novel miR-99b-5p-Zbp1pathway in microglia that contributes to the pathogenesis of schizophrenia. Our data suggest that strategies to increase the levels of miR-99b-5p or inhibitZbp1could become a novel therapeutic strategy.

Triple-negative breast cancer accounts for 10-15% of all breast tumors (TNBC). Triple-negative breast cancer lacks either estrogen or progesterone receptors (ER or PR), producing either too little or too much HER2. (All three tests result in “negative” results for the cells.) These cancers are more common in women under 40 who are Black or have the BRCA1 mutation. TNBC differs from other types of invasive breast cancer in that it has fewer treatment options, a worse prognosis, and grows and spreads more quickly (outcome). So, first of all, the protein of triple-negative breast cancer was collected from the PDB database having the most stable configuration, and a natural bioactive molecule, Scutellarein, was selected. Scutellarein is well-known to possess anti-cancer properties, so its derivatives were chosen to design anticancer drugs through computational tools. In this case, the functional group has applied and modified structural activity relationship methods. Then, the pass prediction score was taken, which indicates the probability of active (Pa) and the probability of inactive (Pi). After that, otherin-silcoapproaches, such as the ADMET parameter, and quantum calculation by Density Functional Theory (DFT), have been conducted. Finally, molecular docking and dynamics have been evaluated against TNBC to determine the binding affinity and stability. Scutellarein derivatives (DM03 at -10.7 kcal/mol, DM04 at -11.0 kcal/mol) have been reported to have a maximum tendency for binding against TNBC. Besides, the molecular dynamic simulation was performed at 100ns and described by root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF), which are much more stable compounds. The pharmacokinetics specifications for a suitable therapeutic candidate were satisfied by these molecules, like as non-carcinogenic, minimal to aquatic and non-aquatic toxicity. Almost all the molecules are highly soluble in the aqueous system. These all-computational data suggested that they might be suitable as a medication for the inhibition of TNBC, and further experimental studies should be carried out.

COVID-19, which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread over the world, posing a global health concern. The ongoing epidemic has necessitated the development of novel drugs and potential therapies for patients infected with SARS-CoV-2. Advances in vaccination and medication development, no preventative vaccinations, or viable therapeutics against SARS-CoV-2 infection have been developed to date. As a result, additional research is needed in order to find a long-term solution to this devastating condition. Clinical studies are being conducted to determine the efficacy of bioactive compounds retrieved or synthesized from marine species starting material. The present study focuses on the anti-SARS-CoV-2 potential of marine-derived phytochemicals, which has been investigated utilizing in in silico, in vitro, and in vivo models to determine their effectiveness. Marine-derived biologically active substances, such as flavonoids, tannins, alkaloids, terpenoids, peptides, lectins, polysaccharides, and lipids, can affect SARS-CoV-2 during the viral particle's penetration and entry into the cell, replication of the viral nucleic acid, and virion release from the cell; they can also act on the host's cellular targets. COVID-19 has been proven to be resistant to several contaminants produced from marine resources. This paper gives an overview and summary of the various marine resources as marine drugs and their potential for treating SARS-CoV-2. We discussed at numerous natural compounds as marine drugs generated from natural sources for treating COVID-19 and controlling the current pandemic scenario.

Cancer is a fatal disorder that affects people across the globe, yet existing therapeutics are ineffective. The development of submicrometer transport for optimizing the biodistribution of systemically provided medications is the focus of nanomedicine. Nanoparticle- (NP-) based treatments may enable the development of novel therapeutic approaches to combat this deadly disorder. In multifunctional, multimodal imaging, and drug delivery carriers, NPs generally play a major role. They have emerged as potential strategies for the invention of innovative therapeutic procedures in the last decade. The exponential growth of nanotechnologies in recent years has increased public awareness of the application of these innovative therapeutic approaches. Many tumor-targeted nanomedicines have been studied in cancer therapy, and there is clear evidence for a significant improvement in the therapeutic index of antineoplastic drugs. Age-related factors such as metabolic and physiological alterations in old age and inadequate animal models are currently understudied in nanomedicine and pharmacology. This review highlighted the most important targeting approaches, as well as public awareness, therapeutic advancements, and future prospects in age-related metabolic variations, and tumor-targeted nanomedicine studies.