Zoonotic virus spill over in human community has been an intensive area of viral pathogenesis and the outbreak of Hantaan virus and severe acute respiratory syndrome coronavirus 2 (SARS CoV2) after late December 2019 caused a global threat. Hantaan virus is second to the COVID-19 outbreak in China with seven cases positive and one death. Both RNA viruses have opposite sense as in (−) for Hantaan virus and (+) for SARS CoV2 but have similarity in the pathogenesis and relevant clinical features including dry cough, high fever, shortness of breath, and SARS associated with pneumonia and certain reported cases with multiple organ failure. Although COVID-19 has global impact with high death toll, Hantaan virus has varyingly high mortality rate between 1% and 40%. Hence, there is a need to explore novel therapeutic targets in Hantaan virus due to its rapid evolution rate in its genetic makeup which governs virulence and target host cells. This review emphasizes the importance of structural and nonstructural proteins of Hantaan virus with relevant insight from SARS CoV2. The envelope glycoproteins such as Gn, Gc, and nucleocapsid protein (N) direct the viral assembly and replication in host cells. Therapeutic treatment has similarity in using ribavirin and extracorporeal membrane oxygenation but lack of efficacious treatment in both cases of SARAS CoV2 and Hantaan virus. Therefore, potential features regarding therapeutic targets for drug discovery for Hantaan viruses are discussed herewith. The conclusive description highlights that N protein is substantially involved in evoking immune response and induces symptoms and could be precursive target for drug discovery studies.

BACKGROUND: Levofloxacin-based triple therapies are considered the standard regimen for eradication of Helicobacter pylori (H. pylori) due to decreased sensitivity to clarithromycin and the optimal duration of therapy is still controversial. Besides, there is no complete evidence about dexlansoprazole efficacy in the eradication of H. pylori. AIM: Our study aimed to determine the effectiveness of triple therapy based on levofloxacin-dexlansoprazole as a standard treatment for H. pylori infection and estimate the effect of H. pylori on lipid profile and hemoglobin (Hb). MATERIALS AND METHODS: A pilot prospective randomized trial of a triple therapy based on levofloxacin-dexlansoprazole for H. pylori eradication was conducted at Damanhour Medical National Institute, Egypt; 66 participants with H. pylori infection received levofloxacin (500 mg/day) plus amoxicillin (1 g/12 h) plus dexlansoprazole (60 mg/day). All medications administrated orally for either 7 days or 10 days. Four weeks after treatment, the eradication was assessed by the stool antigen test. RESULTS: The rate of eradication was 63.6% in levofloxacin, amoxicillin, and dexlansoprazole (LAD) 7-day group, and 90.9% in LAD 10-day group. In addition, laboratory test results showed a significant difference in Hb, low-density lipoprotein, high-density lipoprotein, triglyceride, and total cholesterol levels before and after treatment (P < 0.05). CONCLUSION: LAD 10 days is the least duration that provides maximum efficacy for H. pylori in Egyptian participants. In addition, successful treatment of H. pylori infection may reduce the risk of anemia and dyslipidemia. Furthermore, all members of the patient’s family should be screened for H. pylori to prevent recurrent infection.

BACKGROUND: Dyslipidemias are on the rise and are increasingly being treated with statins. As the metabolism of cholecalciferol and cholesterol are interrelated, reduction in cholesterol synthesis by statins is likely to affect Vitamin D status. OBJECTIVES: (1) The aim is to study the effect of treatment with statins (Atorvastatin/Rosuvastatin) on 25-hydroxy-Vitamin-D (25OHD) among newly detected subjects with dyslipidemia for 6 months (2) To study the impact of 25OHD concentrations on the efficacy of statin treatment. MATERIALS AND METHODS: This was a prospective, balanced randomized (1:1), open-label, parallel-group study, in apparently healthy Indian adult men (south Asian, 40–60 years). At baseline, serum lipids and 25OHD concentrations were measured. Based on the Adult Treatment Panel III guidelines, subjects were divided as per lipid concentrations into controls (who did not require statin treatment) and intervention (who required statin treatment) groups. Random allocation of subjects was done in two groups for receiving intervention for 6 months: Atorvastatin group (n = 52, received Atorvastatin) or Rosuvastatin group (n = 52, received Rosuvastatin). Lipids and 25OHD concentrations were measured at the end line. RESULTS: Atorvastatin group presented significant reduction (P < 0.05) in 25OHD, total cholesterol (TC) and low-density-lipoprotein-cholesterol (LDL-C) concentrations at the end line. In the Rosuvastatin group, significant drop in TC, LDL-C and high-density lipoprotein cholesterol (concentrations (P < 0.05) was observed, while 25OHD concentrations showed no significant change. Mean 25OHD concentrations were significantly correlated with a reduction in LDL-C concentrations in Atorvastatin group. CONCLUSIONS: Treatment with Atorvastatin resulted in a reduction in 25OHD concentrations; further, its efficacy in reducing LDL-C concentrations was related to the 25OHD concentrations.

BACKGROUND AND OBJECTIVE: Chronic hepatitis, cirrhosis, and hepatocellular carcinoma are mainly caused by hepatitis C infection. It is a worldwide predominant pathogen and is one of the main causes of healthcare problem in Asia. In the last few decades, there has been a considerable change in the treatment regimen for hepatitis C virus. The objective of this research was to relate the treatment response with sustained viral response in various therapies which have been the standard of care from time to time. MATERIALS AND METHODS: This hospital-based, retrospective-cum-prospective research span over a period of 2 years; we enrolled hepatitis C patients who attended the Department of Gastroenterology and Hepatology, Government Medical College, Srinagar, since June 2015 till May 2017. Subsequently, the database was prepared, containing all the relevant information about these patients. RESULTS: [INLINE:1] CONCLUSIONS: (i) In retrospective group: The overall efficacy (sustained viral response at 24 weeks [SVR-24]) of pegylated interferon a2a and ribavirin regimen was 90.96%. (ii) In prospective group: The efficacy (SVR) of different regimens was found to be as: sofosbuvir + ribavirin + daclatasvir (SVR-24, 83.33%); sofosbuvir + ribavirin (SVR-12, 94.57%); and sofosbuvir + daclatasvir (SVR-12, 98.00%).

OBJECTIVES: The objectives of this study were to determine the relationship between genetic polymorphisms in gene encodings for CYP3A4 and carbamazepine (CBZ)-induced dose-related side effects in North Indian people with epilepsy. PATIENTS AND METHODS: The current prospective study included 37 patients with CBZ-induced dose-related side effects and 102 patients who did not experience side effects while on CBZ. The genotyping for CYP3A4 allele (CYP3A4*16) was done using real-time polymerase chain reaction (RT-PCR) in Applied Biosystems 7500 RT-PCR System (USA). CBZ was administered in all patients at a dose varying from 15 to 20 mg/kg daily. RESULTS: Various demographic variables were comparable between the groups except that control of seizures was far better in controls. After testing, it was found that none of our patients had the presence of CYP3A4*16 allele. CONCLUSION: CYP3A4*16 allele is not represented significantly in North Indian people with CBZ-induced dose-related side effects.

OBJECTIVE: Patients exposed to chronic sustained hypoxia frequently develop cardiovascular disease risk factors to ultimately succumb to adverse cardiovascular events. In this context, the present study intends to assess the role of cilnidipine (Cil), a unique calcium channel blocker that blocks both L-type and N-type calcium channels, on cardiovascular pathophysiology in face of chronic sustained hypoxia exposure. MATERIALS AND METHODS: The study involved Wistar strain albino rats. The group-wise allocation of the experimental animals is as follows - Group 1, control (21% O₂); Group 2, chronic hypoxia (CH) (10% O₂, 90% N); Group 3, Cil + 21% O₂; and Group 4, CH (10% O₂, 90% N) + Cil (CH + Cil). Cardiovascular hemodynamics, heart rate variability, and endothelial functions (serum nitric oxide [NO], serum endothelial nitric oxide synthase [NOS3], and serum vascular endothelial growth factor [VEGF]) were assessed. Cardiovascular remodeling was studied by histopathological examination of the ventricular tissues, coronary artery (intramyocardial), and elastic and muscular arteries. Normalized wall index of the coronary artery was also calculated. RESULTS AND CONCLUSION: The results demonstrated altered cardiovascular hemodynamics, disturbed cardiovascular autonomic balance, increased levels of VEGF and NOS3, and decreased bioavailability of NO on exposure to chronic sustained hypoxia. The histopathological examination further pointed toward cardiovascular remodeling. Treatment with Cil ameliorated the cardiovascular remodeling and endothelial dysfunction induced by CH exposure, which may be due to its blocking actions on L/N-type of calcium channels, indicating the possible therapeutic role of Cil against CH-induced cardiovascular pathophysiology.

OBJECTIVES: Alzheimer’s disease (AD) is a constant, developing brain impairment that is described as the aggregation of misfolded amyloid-beta-peptide (Ab) and abnormal tau protein in the brain. Stem cell therapy became a favorable candidate for the regeneration of neurodegenerative disorders like AD, but there is still shortage of knowledge about the underlying mechanisms. The goal of this survey was the determination of the necroptotic pathway as the possible mechanism for the effect of human adipose-derived stem cells (hADSCs) in the rat model of AD. MATERIALS AND METHODS: Twelve rats were consumed, dividing into four groups: Control, sham, AD model and AD + stem cell groups. We utilized Nissl and Thioflavin S staining for determining histological changes and immunofluorescent techniques for evaluating necroptotic markers in different regions of the hippocampus. RESULTS: The confirmation of AD model was approved with histological examination. The findings indicated more distinct Thio-S stain and an increased number of dead cells in AD rats comparing to other groups. Alternatively, the dead cells number in the CA3 area significantly lessened in AD + stem cell group comparing to AD group. Data showed that hADSCs significantly decreased the expression of necroptotic markers (receptor-interacting protein 1, receptor-interacting protein 3 and mixed lineage kinase domain-like pseudokinase (MLKL)) in AD + stem cell group compared to AD group in different regions of the hippocampus. CONCLUSION: Our findings revealed that the intravenous injection of hADSCs reduced necroptosis and consequently declined the death of neuronal cells in the hippocampus of AD rats. Keywords:

Treatment of cancer is a major challenge even though the pathophysiology is becoming clearer with time. A number of new chemical entities are developed to target cancer growth inhibition, but the targeted delivery of these products still needs novel research. This is of utmost importance not only for higher efficacy but also for a reduction in systemic toxicity and cost of treatment. Although multiple novel targets and molecules are being researched, most of them could not pass the regulatory approval process, due to low benefit–risk ratio and lack of target specificity. Failure of a majority of these drugs was in part due to their superiority claimed via surrogate markers. Despite these, currently, more than 100 chemotherapeutic agents are in practice. This review paper discusses in detail the molecular basis, drug discovery, and pros and cons over conventional treatment approaches of three novel approaches in cancer therapy, i.e., (i) antibody–drug conjugates, (ii) cancer immunotherapy, and (iii) metronomic chemotherapy. All the drugs developed using these three novel approaches were compared against the established treatment regimens in clinical trials with clinical end points, such as overall survival, progression-free survival, and quality of life.

Multiple options are being tried for the management of 2019-nCoV infection since its pandemic started. Favipiravir (FPV) is one of drugs, which is also being tried for the management of 2019-nCoV infection. The present study aimed to evaluate the efficacy and safety of FPV in published literature. Comparative randomized or nonrandomized controlled clinical trials comparing FPV to the standard of care (SOC)/control or other antiviral agent/combinations were included. A total of 12 databases were searched and identify four studies which were further used for final analysis. The data analysis was done as pooled prevalence using a random effect model by “RevMan manager version 5.4.1 and “R” software. The point estimate, odds ratio (OR) with 95% confidence interval (CI) was calculated for dichotomous data. In the present study, the marginal beneficial effect was seen in the FPV group in overall clinical improvement comparison to SOC/control, i.e., (4 studies, log OR [95% CI] (−0.19 [−0.51, 0.13]). However, in all other outcomes, it was found to be comparable to the SOC/control arm namely “clinical improvement on day 7–10” (3 studies, OR [95% CI] 1.63 [1.07, 2.48]) while “clinical improvement on day 10–14” (3 studies, OR [95% CI] 1.37 [0.24, 7.82]) and viral negativity was seen (4 studies, OR [95% CI] 1.91 [0.91, 4.01]). No difference in efficacy was found between FPV versus lopinavir/ritonavir or arbidol groups. Regarding adverse effects, except for the occurrence of rash (higher in the FPV group), safety was comparable to SOC. In our study, there was a marginal difference between the FPV and the SOC arm in terms of “clinical improvement” on day 7–10 or 10–14, and “virological negativity” on day 10–14.” However, some benefit was observed in a few studies, but it was also comparable to the control drugs or SOC.

Advances in stem cell cultures and human-induced pluripotent stem cells have inculcated interests in a rapidly evolving concept – ”organoids.” These are three-dimensional (3D) structures mimicking some of the phenomena of the real organs at anatomical, multicellular, and functional levels in vitro. Organoids have been proven to be better than two-dimensional cell culture in replicating the functionality, architectural, and geometrical features of tissues in vivo. Recent advancements have led to the generation of models for organ development and disease, finding applications in the drug discovery, screening of novel compounds, and personalized medicine. Since organoids follow the same natural pathway as the normal tissue or pathology, they can be used to study the expression of various genotypes and phenotypic variations across different species. In the light of these advancements, organoids are now being merged with bioengineering to come up with even better and reliable models to predict the disease progression and effectiveness of precision medicines, few of its important applications. This article discusses the various aspects of this emerging concept along with its uses, both in the present times and near future, with a special focus on pharmacological applications.

Paclitaxel-induced photodermatitis is extremely rare despite the frequent use of paclitaxel-trastuzumab combination chemotherapy. A 70-year-old woman with infiltrating intraductal breast cancer developed photodermatitis after ten treatment courses of weekly paclitaxel-trastuzumab combination chemotherapy. Withdrawal of paclitaxel and sun avoidance led to its resolution. A combined effect of solar radiation and enhanced porphyrin synthesis is speculated for photodermatitis in paclitaxel. However, the issue of aberrant porphyrin biosynthesis being causal or an epiphenomenon remains unsettled as elevated porphyrins synthesis does not necessarily cause photosensitivity in all treated cases. The relevant literature on paclitaxel-induced photodermatitis and pathomechanism involved is reviewed.