Antimicrobial Resistance

Klebsiella pneumoniae (K. pneumoniae) pose an emerging threat to public health sector worldwide. They are one of the potent nosocomial pathogens and cause variety of infections including pneumonia, septicaemia, wound infections, urinary tract infections and catheter-associated infections. From the last two decades, these pathogens are becoming more powerful due to the acquisition of resistomes on different types of plasmids and transposons. There are four main mechanisms of antibacterial resistance such as efflux pump, target alteration, membrane permeability and notably enzymes hydrolysis. K. pneumoniae produce different types of enzymes but most importantly extended spectrum-β-lactamase (ESBL), carbapenemase and metallo-β-lactamase (MBL). K. pneumoniae carbapenemases (KPCs) and New Delhi metallo-β-lactamase (NDM) producing isolates displayed resistance not only against the β-lactam drugs (penicillins, cephalosporins and carbapenems) but also to other classes of antibiotics (aminoglycosides and quinolones). Therapeutic options available to treat serious infections caused by these extensively drug-resistant pathogens are limited to colistin, tigecycline and fosfomycin. Hence, combination therapy has also been recommended to treat such bacteria with clinical side effects, therefore, new treatment regime must be required. Moreover, we are relying on conventional diagnostic tools, however, novel techniques must be required for robust identification of multi-drug-resistant bacteria

Hurdles in Vaccine Development against Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide and also forms a serious threat for the elderly. Vaccination could significantly relieve the burden of the RSV disease. However, unfortunately there is no licensed vaccine available so far. This is partly due to disastrous outcome of a clinical trial of formalin-inactivated RSV (FI-RSV) in children in 1960s; leading to enhanced respiratory disease upon natural infection. These findings contributed significantly to the delay of RSV vaccine development. Other key obstacles in development of RSV vaccine such as a peak of severe disease at 2–3 months of age, challenging biochemical behavior of key vaccine antigens and dependence on animal models that may not truly reflect human disease processes. These challenges could be overcome through maternal immunization, structure-based engineering of vaccine antigens, the design of a novel platform for safe infant immunization, and the development of improved animal models. Currently, several vaccine candidates are in pre-clinical and clinical trials targeting the diverse age groups; young children or older adults from the infection or can reduce incidence, mortality and morbidity among the RSV infected individuals

Association of renal biomarkers in COVID-19 patients: A retrospective study

Background: The new severe acute respiratory syndrome coronavirus 2 is the cause of the transmissible sickness known as coronavirus disease 2019 (COVID-19) (SARS-CoV-2). Although it often presents as an acute respiratory infection, it can also have a negative impact on the kidneys, heart, gastrointestinal, and nervous system. The aims of this study to find out the association of renal biomarkers among dialysis patients in COVID-19 positive and negative. Methods: A retrospective study was conducted in the Department of medical laboratory technology, the university of Haripur, Khyber Pakhtunkhwa, Pakistan. A Total of 129 Dialysis patients blood samples were collected from March 2022 to April 2022 in which 13 males and 20 females are COVID-19 positive while 41 males and 55 females are COVID-19 negative. The obtained data was statistically analyzed by using PRISM version 5.0 by applying two-way ANOVA and Comparisons between Covid positive and negative patients RFTs by using Bonferroni posttest. Results: Male patients with chronic kidney disease (on dialysis) with COVID-19 negative and positive their mean urea difference was 95.20mg/dl and 159.6mg/dl, while COVID-19 negative and positive the mean creatinine difference was 8.534mg/dl and 13.81mg/dl respectively. While there was no significance difference in uric acid concentration in CKD patients with COVID-19 negative and positive. Female patients with chronic kidney disease (on dialysis) with COVID-19 negative and positive their mean urea difference was 103.20mg/dl and 152.6mg/dl, while COVID-19 negative and positive the mean creatinine difference was 8.114mg/dl and 8.584mg/dl respectively. While there was no significance difference in uric acid concentration in CKD patients with COVID-19 negative and positive. Conclusion: This study concludes that there is positive relationship or association of renal biomarkers in COVID-19 positive patients. Significance association between urea and creatinine in COVID-19 positive

Anticancer potential of phytochemicals against breast cancer: Molecular docking and simulation approach

Breast cancer malignancy is prevailing among the women not only from the developing countries but also from the developed one at the rate of 18% of total population worldwide. One of the main causes of breast cancer is estrogen receptor alpha. Overexpression of estrogen receptor is seen in number of cases of breast cancer. Tamoxifen was used as a reference drug in present study. Almost 80,000 species of plants are used as a source of medicines. Current study was totally based on the screening of phytochemicals to find out the biomolecules having strong bonding actions as compared to tamoxifen. Present study exhibited that 10 molecules (kushenol K, silybin,  taxifolin 3-O-acetate, rosemarinic acid, secundifloran, kushenol N, kurarinol, podophyllotoxone, AC1LCW2L, leachianone G)  have successful and potential binding with the target molecule as compared to tamoxifen. These molecules can be used for the treatment of breast cancer and birth control

Potential of plant alkaloids as dengue NS3 protease inhibitors: Molecular docking and simulation approach

Dengue infection has become a worldwide health problem and infection rate is increasing each year. Alkaloids are important phytochemicals of medicinal plant and can be used as vaccine candidates for viruses. Therefore, present study was designed to find potential alkaloids inhibitors against the Dengue virus NS2B/NS3 protease which can inhibit the viral replication inside the host cell. Through molecular docking it was investigated that most of the alkaloids bound deeply in the binding pocket of Dengue virus NS2B/NS3 protease and had potential interactions with catalytic triad. Five alkaloids (6-desmethylthalifaboramin; 3,5-dihydroxythalifaboramine; Betanin; Reserpic acid and  Tubulosine) successfully blocked the catalytic triad of NS2B/NS3 protease and these alkaloids can serve as a potential drug candidate to stop viral replication. It can be concluded from this study that these alkaloids could serve as important inhibitors to inhibit the replication of DENV and need further in-vitro investigations to confirm their efficacy and drug ability

Anticancer screening of medicinal plant phytochemicals against Cyclin-Dependent Kinase-2 (CDK2): An in-silico approach

Background: Cyclin-Dependent Kinase-2 (CDK2) is a member of serine/threonine protein kinases family and plays an important role in regulation of various eukaryotic cell division events. Over-expression of CDK2 during cell cycle may lead to several cellular functional aberrations including diverse types of cancers (lung cancer, primary colorectal carcinoma, ovarian cancer, melanoma and pancreatic carcinoma) in humans. Medicinal plants phytochemicals which have anticancer potential can be used as an alternative drug resource.Methods: This study was designed to find out anticancer phytochemicals from medicinal plants which could inhibit CDK2 with the help of molecular docking technique. Molecular Operating Environment (MOE v2009) software was used to dock 2300 phytochemicals in this study.Results: The outcome of this study shows that four phytochemicals Kushenol T, Remangiflavanone B, Neocalyxins A and Elenoside showed the lowest S-score (-17.83, -17.57, -17.26, -17.17 respectively) and binds strongly with all eight active residues Tyr15, Lys33, Ileu52, Lys56, Leu78, phe80, Asp145 and Phe146 of CDK2 binding site. These phytochemicals could successfully inhibit the CDK2.Conclusion: These phytochemicals can be considered as potential anticancer agents and used in drug development against CDK2. We anticipate that this study would pave way for phytochemical based novel small molecules as more efficacious and selective anti-cancer therapeutic compounds

Thermal Performance Analysis of Various Heat Sinks Based on Alumina NePCM for Passive Cooling of Electronic Components: An Experimental Study

In the modern digital world, electronic devices are being widely employed for various applications where thermal performance represents a significant technical challenge due to continued miniaturization, high heat generated in the system, and non-uniform high-temperature causing failure. Phase change materials (PCMs) owing to the immense heat of fusion are primarily considered for thermal management, but their insulating properties hedge their applications in electronics cooling. Nano-enhanced phase change materials (NePCMs) have the ability to improve the thermal conductivity of PCM, decrease system temperature and escalate the operating time of devices. Accordingly, the current study focused on the experimental investigations for the thermal performance of three heat sinks (HS) with different configurations such as a simple heat sink (SHS), a square pin-fins heat sink (S pfHS), and Cu foam integrated heat sink (Cu fmHS) with various alumina nanoparticles mass concentrations (0.15, 0.20 and 0.25 wt%) incorporated in PCM (RT-54HC) and at heat flux (0.98–2.94 kW/m 2). All HSs reduced the base temperature with the insertion of NePCM compared to the empty SHS. The experimental results identified that the thermal performance of Cu fmHS was found to be superior in reducing base temperature and enhancing working time at two different setpoint temperatures (SPTs). The maximum drop in base temperature was 36.95%, and a 288% maximum working time enhancement was observed for Cu fmHS. Therefore, NePCMs are highly recommended for the thermal management of the electronic cooling system

Thiamethoxam toxicity: a review in one-health perspective

Extensive and frequent use of pesticides has induced numerous abnormalities in target and non-target exposed organisms. Among different various pesticides, neonicotinoids are extensively employed in agro-production sectors. Thiamethoxam (TMX) plays an essential role in keeping the crop safe from insect attack, but on the other hand, it has been reported to induce adverse effects in both humans and animals. Previously, it was thought that neonicotinoids have low toxicity potential in mammals, but widespread use has made it evident that these pesticides have serious toxic effects on both invertebrates and vertebrates. Extensive applications of pesticides also pose serious eco-toxicological threats to aquatic and terrestrial organisms in the ecosystem. This review describes the chemistry, pharmacodynamics, and toxic effects of various TMX on living organisms. Moreover, this review summarizes the excretion/deposition of TMX in different tissues along with potentially adverse effects on production potential, immunity, blood parameters, and male/female reproductive systems. Though the pros of TMX surpass the cons, its reported intrinsic toxicity stresses the need to develop new pesticides that have high potency with little harm to humans and animals. Hence, there is a need for hours to address knowledge gaps related to TMX and design effective rational usage of TMX strategies to keep the ecosystem safe from the potentially harmful effects of TMX