Functional consequences of familial ALS-associated SOD1L84F in neuronal and muscle cells.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder characterized by progressive skeletal muscle denervation and loss of motor neurons that results in muscle atrophy and eventual death due to respiratory failure. Previously, we identified a novel SOD1L84F variation in a familial ALS case. In this study, we examined the functional consequences of SOD1L84F overexpression in the mouse motor neuron cell line (NSC-34). The cells expressing SOD1L84F showed increased oxidative stress and increased cell death. Interestingly, SOD1L84F destabilized the native dimer and formed high molecular weight SDS-resistant protein aggregates. Furthermore, SOD1L84F also decreased the percentage of differentiated cells and significantly reduced neurite length. A plethora of evidence suggested active involvement of skeletal muscle in disease initiation and progression. We observed differential processing of the mutant SOD1 and perturbations of cellular machinery in NSC-34 and muscle cell line C2C12. Unlike neuronal cells, mutant protein failed to accumulate in muscle cells probably due to the activated autophagy, as evidenced by increased LC3-II and reduced p62. Further, SOD1L84F altered mitochondrial dynamics only in NSC-34. In addition, microarray analysis also revealed huge variations in differentially expressed genes between NSC-34 and C2C12. Interestingly, SOD1L84F hampered the endogenous FUS autoregulatory mechanism in NSC-34 by downregulating retention of introns 6 and 7 resulting in a two-fold upregulation of FUS. No such changes were observed in C2C12. Our findings strongly suggest the differential processing and response towards the mutant SOD1 in neuronal and muscle cell lines.

Targeted inhibition of NRF2 reduces the invasive and metastatic ability of HIP1 depleted lung cancer cells.

BACKGROUND: Non-Small Cell Lung Cancer (NSCLC) presents as a highly metastatic disease with Kras and P53 as prevalent oncogenic driver mutations. Endocytosis, through its role in receptor recycling and enrichment, is important for cancer cell proliferation and metastasis. Huntingtin Interacting Protein 1 (HIP1) is a clathrin mediated endocytic adapter protein found overexpressed in different cancers. However, conflicting roles both as a tumour promoter and suppressor are reported. HIP1 expression is found repressed at advanced stages and some HIP1-ALK fusions are reported in NSCLC patients. However, the molecular mechanisms and implications of HIP1 depletion are not completely understood. METHODS: HIP1 depletion was performed using siRNA transient transfection and validated using immunoblotting for each experiment. Gene expression dataset from TCGA, GTEX and GEO databases was analysed to explore HIP1 expression in Lung cancer patients. Kaplan-Meier Plotter database was used to analyse the survival correlation between HIP1 mRNA expression in lung cancer patients. HIP1 depleted A549 cells were analysed for deregulated global proteome using label-free LC-MS and this data is available via ProteomeXchange with identifier PXD054307. Various functional assays such as matrigel based invasion, trans-well migration, soft agar colony and angiogenesis tube formation were performed after HIP1 depletion. NRF2 inhibitor was used after HIP1 knockdown to assess its effect on invasion and soft agar colony formation. RESULTS: In silico analysis of HIP1 transcript expression reveals that it is reduced in high-grade and metastatic lung cancer patients correlating with poor survival. Global proteome profiling reveals that HIP1 depleted A549 cells are enriched in pathways associated with metabolism, proliferation and survival. Molecular and functional analysis indicate higher invasive ability of HIP1 depleted cells. The secretome from HIP1 depleted cells also increases the angiogenic potential of HUVEC cells. NRF2 inhibition significantly reverses invasion of HIP1 depleted NSCLC cells with different driver mutations. CONCLUSION: Our study shows that HIP1 depletion leads to activation of various molecular pathways responsible for cell proliferation and survival. Additionally, enhancement of invasion and anchorage-independent growth in HIP1 depleted subsets of NSCLC cells is via upregulation of NRF2 and can be reversed by its inhibitor.

Drug target therapy and emerging clinical relevance of exosomes in meningeal tumors.

Meningioma is the most common central nervous system (CNS) tumor. In recent decades, several efforts have been made to eradicate this disease. Surgery and radiotherapy remain the standard treatment options for these tumors. Drug therapy comes to play its role when both surgery and radiotherapy fail to treat the tumor. This mostly happens when the tumors are close to vital brain structures and are nonbenign. Although a wide variety of chemotherapeutic drugs and molecular targeted drugs such as tyrosine kinase inhibitors, alkylating agents, endocrine drugs, interferon, and targeted molecular pathway inhibitors have been studied, the roles of numerous drugs remain unexplored. Recent interest is growing toward studying and engineering exosomes for the treatment of different types of cancer including meningioma. The latest studies have shown the involvement of exosomes in the theragnostic of various cancers such as the lung and pancreas in the form of biomarkers, drug delivery vehicles, and vaccines. Proper attention to this new emerging technology can be a boon in finding the consistent treatment of meningioma.

Rheumatoid arthritis: advances in treatment strategies.

Rheumatoid arthritis (RA) is characterised by severe joint and bone damage due to heightened autoimmune response at the articular sites. Worldwide annual incidence and prevalence rate of RA is 3 cases per 10,000 population and 1%, respectively. Several genetic and environmental (microbiota, smoking, infectious agents) factors contribute to its pathogenesis. Although convention treatment strategies, predominantly Disease Modifying Anti Rheumatic Drugs (DMARDs) and Glucocorticoids (GC), are unchanged as the primary line of treatment; novel strategies consisting of biological DMARDs, are being developed and explored. Personalized approaches using biologicals targetspecific pathways associated with disease progression. However, considering the economic burden and side-effects associated with these, there is an unmet need on strategies for early stratification of the inadequate responders with cDMARDs. As RA is a complex disease with a variable remission rate, it is important not only to evaluate the current status of drugs in clinical practice but also those with the potential of personalised therapeutics. Here, we provide comprehensive data on the treatment strategies in RA, including studies exploring various combination strategies in clinical trials. Our systematic analysis of current literature found that conventional DMARDs along with glucocorticoid may be best suited for early RA cases and a combination of conventional and targeted DMARDs could be effective for treating seronegative patients with moderate to high RA activity. Clinical trials with insufficient responders to Methotrexate suggest that adding biologicals may help in such cases. However, certain adverse events associated with the current therapy advocate exploring novel therapeutic approaches such as gene therapy, mesenchymal stem cell therapy in future.

Association of underlying comorbidities and progression of COVID-19 infection amongst 2586 patients hospitalised in the National Capital Region of India: a retrospective cohort study.

This study is conducted to observe the association of diabetes (DM), hypertension (HTN) and chronic kidney disease (CKD) on the prognosis and mortality of COVID-19 infection in hospital admitted patients with above mentioned comorbidities. This is a single centre, observational, retrospective study carried out at Sir Ganga Ram Hospital, Delhi, India. The burden of comorbidities on the prognosis and clinical outcome of COVID-19 patients admitted patients from April 8, 2020, to October 4, 2020. Chi-square and relative risk test were used to observe the association of comorbidities and disease prognosis. A total of 2586 patients were included in the study consisting of 69.6% of male patients. All the comorbidities were significantly associated with ICU admission and mortality. The relative risk showed that CKD is most prone to severity as well as mortality of the COVID-19 infection followed by HTN and DM. Further with the increase in number of underlying comorbidities, the risk of ICU admission and mortality also increases. Relative risk of the severity of COVID-19 infection in younger patients with underlying comorbidities are relatively at higher risk of severity of disease as well as to mortality compared to the elderly patients with similar underlying condition. Similarly, it is found that females are relatively at higher risk of mortality as compared to the males having same comorbid conditions except for the hypertensive patients. Diabetes, hypertension and CKD, all are associated with progression of COVID-19 disease to severity and higher mortality risk. The number of underlying comorbid condition is directly proportional to the progression of disease severity and mortality.

Indian food habit & food ingredients may have a role in lowering the severity & high death rate from COVID-19 in Indians: findings from the first nutrigenomic analysis.

Background & objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level. Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated. Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate. Interpretation & conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings.

Integrated view of molecular diagnosis and prognosis of dengue viral infection: future prospect of exosomes biomarkers.

Dengue viruses (DENVs) are the viruses responsible for dengue infection which affects lungs, liver, heart and also other organs of individuals. DENVs consist of the group of four serotypically diverse dengue viruses transmitted in tropical and sub-tropical countries of world. Aedes mosquito is the principal vector which spread the infection from infected person to healthy humans. DENVs can cause different syndromes depending on serotype of virus which range from undifferentiated mild fever to dengue hemorrhagic fever resulting in vascular leakage due to release of cytokine and Dengue shock syndrome with fluid loss and hypotensive shock, or other severe manifestations such as bleeding and organ failure. Increase in dengue cases in pediatric population is a major concern. Transmission of dengue depends on various factors like temperature, rainfall, and distribution of Aedes aegypti mosquitoes. The present review describes a comprehensive overview of dengue, pathophysiology, diagnosis, treatment with an emphasis on potential of exosomes as biomarkers for early prediction of dengue in pediatrics.

Spread and Endemicity of Cholera in India: Factors Beyond the Numbers.

Cholera outbreaks currently account for 1.3 to 4.0 million cases and cause between 21 000 and 143 000 deaths worldwide. Cholera is preventable by proper sanitization and immunization; however, in many developing nations such as India, cholera disease is endemic. The surveillance system in India does not adequately capture the actual number of cases. As a result, it is important to utilize limited public health resources correctly in India and other developing counties more effectively to reach vulnerable communities. In this study, we analyze how studies make sense of cholera transmission and spread in India from 1996 to 2015. Furthermore, we analyze how a more sensitive surveillance system can contribute to cholera eradication by giving rise to outbreak preparedness.

Comprehensive overview of extracellular vesicle proteomics in meningioma: future strategy.

BACKGROUND: Meningioma arising from meninges is one among the various types of brain tumors. Others are, astrocytomas originating from astrocyte, oligodendrogliomas originating from oligodendrocyte, Ependymomas originating from ependymal cells and medulloblastomas originating from neurons. Current knowledge of molecular biology, genetics and epigenetics of meningioma is not sufficient. Therefore, In depth understanding of the mechanism of meningioma formation and progression is needed for its treatment and management. Grade I Grade I meningiomas are majorly classified as grade I, grade II and grade III. Meningioma can be indolent, slow growing or can be invasive and metastatic which can recurre. Grade I meningioma can be removed by surgery in comparison to invasive meningioma which may recurre with high propensity. This property of recurrence is responsible for high morbidity and mortality. Meningioma are majorly classified into three classes namely grade I, grade II, grade III. Protein biomarkers are considered as promising candidates for the diagnosis of meningioma. STUDY: Various studies done on differential expression of proteins have shown increased expression of EGFR, NEK9, EPS812, CKAP4, SET and STAT2, in all the three grades of meningioma. Additionally, some proteins like HK2 are overexpressed in grade II and grade III meningioma than in grade I meningioma. Protein Markers, found on extracellular vesicles of different grades of meningioma can serve the same purpose. A test done on a sample of any kind of body fluid like blood, tear, saliva, urine etc. for recognizing the circulating cancer cells or DNA and extracellular vesicles released from them to help detecting the early stage of cancer is known as liquid biopsy. Solid biopsy has several limitations as compared to liquid biopsy. This is because the samples can be easily collected and studied in case of liquid biopsy. Exosomes are related with liquid biopsy and hence provide platform for better diagnosis, prognosis and treatment of any type of cancer including meningioma. Exosomal tetraspanin are important example of exosomal biomarkers. The tetraspanin network is a molecular scaffold which connects various proteins for signal transduction. CONCLUSION: This study tells about the utility of proper knowledge of extracellular vesicle proteins and their profiles in different grades, which can help in better understanding of pathogenesis, diagnosis, prognosis and treatment of meningioma. In Addition to use of these proteins as biomarkers, role of exosomes in currently available therapeutic approaches has been discussed.

High soluble interleukin-2 receptor values in Indian paediatric & adult controls - Need for population-specific threshold in the diagnosis of haemophagocytic lymphohistiocytosis.

Background & objectives: Elevated soluble interleukin-2 receptor (sIL2R) is a diagnostic criterion for haemophagocytic lymphohistiocytosis (HLH). International guidelines propose a 2400 U/ml cut-off or individual laboratory-defined cut-off. However, sIL2R normal values are so far not known in Indians. So, this study was undertaken to measure sIL2R in healthy children and adults to establish age-related reference values. Methods: Healthy controls and cases (participants with persistent fever, organomegaly, cytopenias and biochemical markers of HLH) were prospectively enrolled. Serum sIL2R was measured by double-sandwich enzyme immunoassay in a standardization batch to determine the optimum cut-off value using receiver operator characteristic curve and was subsequently validated. Results: One hundred and forty six age- and sex-matched children (80 controls and 66 suspected HLH cases) and 55 adults (49 controls and 6 suspected HLH cases) were prospectively enrolled. The optimal sIL2R cut-off ≥23 ng/ml was defined as raised sIL2R in the standardization batch. No controls had sIL2R ≥23 ng/ml in the validation batch. In healthy controls, median sIL2R (interquartile range) decreased with increasing age from 9.0 ng/ml (6.6-13.4) below five years of age to 3.2 ng/ml (2.8-5.1) in adults. Proposed upper limit of normal value for sIL2R is 17.4 ng/ml in less than five year, 12.2 ng/ml in 5-9 yr, 6.7 ng/ml in 10-17 yr and 5.2 ng/ml in ≥18 yr. sIL2R accuracy to diagnose HLH marginally improved with age-appropriate cut-off. Interpretation & conclusions: Paediatric controls in India showed higher sIL2R levels than most studies conducted in other countries, except for some reports in Chinese and Russian populations. Age-appropriate reference values of sIL2R in a specific population may be considered to determine elevated sIL2R as a marker of HLH.

Potentials of "stem cell-therapy" in pancreatic cancer: An update.

In recent times, cell-therapies like T-activated cells, dendritic cells and natural killer cells have shown increasing promise in treating cancers as evidenced by both animal and human studies in the literature. In addition, stem cells are also being considered as potent anti-cancer agents since they act through multi-pronged approaches (chemokines, cytokines, paracrine action). In this review, we have attempted to discuss the inferences of studies that have used different sub-types of stem cells namely mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs) and neural stem cells (NSCs) in in-vitro/in-vivo mice and/or human studies as a treatment modality for pancreatic cancer. Pancreatic cancers are diagnosed in late/metastatic stages hence limiting its progress to partial/disease-free status. Recent literature supports evidences of stem cell therapy in pancreatic cancer with promising results; yet their impact remains inconclusive due to limited studies in human subjects. With reference to the treatment options for pancreatic cancer, the most studied sub-type of stem cells was HSCs as evident from the available clinical trials. The suggested mechanism of the HSC-transplantation is presumably via the graft-versus-tumor effect that elicits an anti-tumor immune response activated by the T-cell repertoires. On the other hand, the property of MSCs like tropism, migration to tumor site and activation of host immune cells by its secretome, appear to be able to regulate pancreatic tumor microenvironment. Further, drug delivery potential could be mediated via engineered MSCs to enhance the bioavailability of drug/prodrug at tumor site. Conclusively, stem cells have shown great potentials as next-generation therapeutic options.

Artificial Intelligence and Deep Learning: The Future of Medicine and Medical Practice.

ABSTRACT: Artificial Intelligence (AI) and access to "Big Data" together with the evolving techniques in biotechnology will change the medical practice a big way. Many diseases such as type II diabetes will no longer be considered as a single disease. Many familiar cancers such as cancer of liver or pancreas will have hundreds of subtypes whose management will be very different. The way we think about diseases will change. It will no longer be possible for clinicians to make a diagnosis, remember the names of diseases, the names of drugs or management protocols without the help of computers. As computer intelligence becomes more important than human intelligence in deciding diagnosis and treatment there will be a paradigm in the role of doctors. Internet, computers and social media will become more important than individuals in decision making. As a result, medicine will go more and more egalitarian ("wiki") with increasing community participation in health decision making and management. A socialistic pattern will evolve over time globally as an adaptive reaction to the pressures put by artificial intelligence. This is because the individual differences in knowledge or intellect between human beings will become less apparent compared to the super powers of artificial intelligence. Qualities which are unique for humans such as compassion, empathy and emotional care will decide the professional success of future physicians even more than today. Today we are using artificial intelligence in diagnosis and prediction to help clinicians. Clinical algorithms and human experience cannot be replaced by machines. It will take many years to completely merge or replace humans with machines. However, we need to modify our medical education system in order to prepare the medical community and sensitize the society well in advance for a smooth transition.

A Retrospective Review of Hospital-Based Data on Enteric Fever in India, 2014-2015.

Background: Enteric fever remains a threat to many countries with minimal access to clean water and poor sanitation infrastructure. As part of a multisite surveillance study, we conducted a retrospective review of records in 5 hospitals across India to gather evidence on the burden of enteric fever. Methods: We examined hospital records (laboratory and surgical registers) from 5 hospitals across India for laboratory-confirmed Salmonella Typhi or Salmonella Paratyphi cases and intestinal perforations from 2014-2015. Clinical data were obtained where available. For laboratory-confirmed infections, we compared differences in disease burden, age, sex, clinical presentation, and antimicrobial resistance. Results: Of 267536 blood cultures, 1418 (0.53%) were positive for S. Typhi or S. Paratyphi. Clinical data were available for 429 cases (72%); a higher proportion of participants with S. Typhi infection were hospitalized, compared with those with S. Paratyphi infection (44% vs 35%). We observed resistance to quinolones among 82% of isolates, with cases of cephalosporin resistance (1%) and macrolide resistance (9%) detected. Of 94 participants with intestinal perforations, 16 (17%) had a provisional, final, or laboratory-confirmed diagnosis of enteric fever. Discussion: Data show a moderate burden of enteric fever in India. Enteric fever data should be systematically collected to facilitate evidence-based decision-making by countries for typhoid conjugate vaccines.

CRISPR/Cas9: an overview of recent developments and applications in cancer research.

CRISPR-Cas9 has risen as a potent gene editing method with vast potential across numerous domains, including its application in cancer research and therapy. This review article provides an extensive overview of the research that has been done so far on CRISPR-Cas9 with an emphasis on how it could be utilized in the treatment of cancer. We go into the underlying ideas behind CRISPR-Cas9, its mechanisms of action, and its application for the study of cancer biology. Furthermore, we investigate the various uses of CRISPR-Cas9 in cancer research, spanning from the discovery of genes and the disease to the creation of novel therapeutic approaches. We additionally discuss the challenges and limitations posed by CRISPR-Cas9 technology and offer insights into the potential applications and future directions of this cutting-edge field of research. The article intends to consolidate the present understanding and stimulate more research into CRISPR-Cas9's promise as a game-changing tool for cancer research and therapy.

Unraveling the genetic landscape of pulmonary arterial hypertension in Indian patients: A transcriptome study.

BACKGROUND: Pulmonary hypertension (PH) is the abnormal elevation of pressure in the pulmonary vascular system, with various underlying causes. A specific type of PH is pulmonary arterial hypertension (PAH), a severe condition characterized by high pulmonary arterial pressure resulting from structural changes in distal pulmonary vessels, altered arterial tone, and inflammation. This leads to right ventricular hypertrophy and heart failure. The molecular mechanisms behind PAH are not well understood. This manuscript aims to elucidate these mechanisms using the genetic tool, aiding in diagnosis and treatment selection. METHOD: In our present study, we have obtained blood samples from both patients with pulmonary arterial hypertension (PAH) and healthy individuals. We conducted a comparative transcriptome analysis to identify genes that are either upregulated or downregulated in PAH patients when compared to the control group. Subsequently, we carried out a validation study focusing on the log2-fold downregulated genes in PAH, employing Quantitative Real-Time PCR for confirmation. Additionally, we quantified the proteins encoded by the validated genes using the ELISA technique. RESULTS: The results of the transcriptome analysis revealed that 97 genes were significantly upregulated, and 6 genes were significantly downregulated. Among these, we chose to focus on and validate only four of the downregulated genes, as they were directly or indirectly associated with the hypertension pathway. We also conducted validation studies for the proteins encoded by these genes, and the results were consistent with those obtained in the transcriptome analysis. CONCLUSION: In conclusion, the findings of this study indicate that the four validated genes identified in the context of PAH can be further explored as potential targets for both diagnostic and therapeutic applications.

Quantitative tissue analysis reveals AK2, COL1A1, & PLG protein signatures: Targeted therapeutics for meningioma.

BACKGROUND: Meningioma is the most prevalent primary intracranial brain tumor and accounts for one-third of all CNS tumors. Meningioma is known to be the most common yet life-threatening brain tumor with a higher recurrence rate. Globally, there is an increase in the healthcare burden due to meningioma and hence in its research. The present clinical approach includes surgical resection, chemotherapy, and radiation therapies to which the malignancy does not seem to respond efficiently. Targeted therapies and molecular markers provide elite patient treatment and care for individuals suffering from meningiomas as compared to conventional measures. Although there is proteomic data on meningioma the knowledge of potential biomarkers differentiating the grades is scarce. To identify the best set of biomarkers, validation of reported markers in large and independent sample cohorts in the future is necessary. METHODS: A total of 12 samples, 3 each of control (which made pool 1) Meningioma grade I (which made 2 sets: pool 2 and pool 3), and Meningioma grade II (which made pool 4) were taken for LC-MS/MS. After this, the expression of three proteins was checked by immunocytochemistry, flow cytometry, and western blotting. RESULTS: Protein expression was analyzed using various techniques like mass spectrometry, immunocytochemistry, flow cytometry, and western blotting. Mass spectrometry is the most commonly used standard and reliable technique for identifying and quantifying protein expression. We got three highly upregulated proteins namely AK2, COL1A1, and PLG using this technique. The biomarker potential of these proteins was further checked by ICC, western blotting, and flow cytometry. Three important proteins were found to be upregulated namely AK2 (Adenylate Kinase 2), COL1A1 (Collagen 1A1), and PLG (Plasminogen). The order of increased protein expression was control < MG grade I < MG grade II according to mass spectrometry and western blotting. In immunocytochemistry, we found that COL1A1 expression increases significantly with grades in comparison to control. Similarly, AK2 and PLG also showed little increase but not as much as COL1A1. In flow cytometry, PLG showed higher upregulation in grades than control. While AK2 and COL1A1 showed little increase in expression in grades than control. All techniques, especially mass spectrometry and western blotting presented higher expression of these proteins in grades as compared to control. CONCLUSIONS: In the quest to find a suitable therapeutic marker, this study incorporates quantitative labeling and detection followed by flow cytometry, Immunocytochemistry, and western blotting for early diagnosis and treatment of meningioma. The article further explores the efficacy of some proteins namely AK2, COL1A1 & PLG to be the targeted molecules.

An update on SARS-CoV-2 immunization and future directions.

Millions of people have died as a result of SARS-CoV-2, which was first discovered in China and has since spread globally. Patients with SARS-CoV-2 infection may show a range of symptoms, including fever, coughing, and shortness of breath, or they may show no symptoms at all. To treat COVID-19 symptoms and avoid serious infections, many medications and vaccinations have been employed. However, to entirely eradicate COVID-19 from the world, next-generation vaccine research is required because of the devastating consequences it is having for humanity and every nation's economy. Scientists are working hard to eradicate this dangerous virus across the world. SARS-CoV-2 has also undergone significant mutation, leading to distinct viral types such as the alpha, beta, gamma, delta, and omicron variants. This has sparked discussion about the effectiveness of current vaccines for the newly formed variants. A proper comparison of these vaccinations is required to compare their efficacy as the number of people immunized against SARS-CoV-2 globally increases. Population-level statistics evaluating the capacity of these vaccines to reduce infection are therefore being developed. In this paper, we analyze the many vaccines on the market in terms of their production process, price, dosage needed, and efficacy. This article also discusses the challenges of achieving herd immunity, the likelihood of reinfection, and the importance of convalescent plasma therapy in reducing infection.

Comprehensive overview of 2022 human monkeypox outbreak and its pathology, prevention, and treatment: A strategy for disease control.

The 2022 Monkeypox virus, an evolved DNA strain originating in Africa, exhibits heightened human-to-human transmissibility and potential animal transmission. Its host remains unidentified. While its initial slow transmission rate restrained global impact, 2022 saw a surge in cases, causing widespread concern in over 103 countries by September. This virus's distinctive human-to-human transmission marks a crucial shift, demanding a prompt revaluation of containment strategies. However, the host source for this shift requires urgent research attention. Regrettably, no universal preventive or curative methods have emerged for this evolved virus. Repurposed from smallpox vaccines, only some vaccinations offer a partial defense. Solely one therapeutic drug is available. The article's essence is to provide a comprehensive grasp of the virus's epidemiology, morphology, immune invasion mechanisms, and existing preventive and treatment measures. This knowledge equips researchers to devise strategies against its spread and potential public health implications.

Donor-Derived Cell-Free DNA as a Non-Invasive Biomarker for Graft Rejection in Kidney Transplant Recipients: A Prospective Study among the Indian Population.

Monitoring graft health and detecting graft rejection is crucial for the success of post-transplantation outcomes. In Western countries, the use of donor-derived cell-free DNA (dd-cfDNA) has gained widespread recognition as a diagnostic tool for kidney transplant recipients. However, the role of dd-cfDNA among the Indian population remains unexplored. The recipients were categorized into two groups: the post-transplant recipient (PTR) group (n = 16) and the random recipient (RR) group (n = 87). Blood samples were collected daily from the PTR group over a 7-day period, whereas the RR group's samples were obtained at varying intervals. In this study, we used a targeted approach to identify dd-cfDNA, which eliminated the need for genotyping, and is based on the minor allele frequency of SNP assays. In the PTR group, elevated dd-cfDNA% levels were observed immediately after transplantation, but returned to normal levels within five days. Within the RR group, heightened serum creatinine levels were directly proportional to increased dd-cfDNA%. Sixteen recipients were advised to undergo biopsy due to elevated serum creatinine and other pathological markers. Among these sixteen recipients, six experienced antibody-mediated rejection (ABMR), two exhibited graft dysfunctions, two had active graft injury, and six (37.5%) recipients showed no rejection (NR). In cases of biopsy-proven ABMR and NR, recipients displayed a mean ± SD dd-cfDNA% of 2.80 ± 1.77 and 0.30 ± 0.35, respectively. This study found that the selected SNP assays exhibit a high proficiency in identifying donor DNA. This study also supports the use of dd-cfDNA as a routine diagnostic test for kidney transplant recipients, along with biopsies and serum creatinine, to attain better graft monitoring.

Evaluation of T and B cell immunophenotyping and antibody response post Covid-19 vaccination.

PURPOSE: To evaluate T and B cell subsets and IgG antibodies in response to SARS-CoV-2 post COVID-19 vaccination. METHODS: A total of 50 healthy adults (18-60 years) receiving anti-SARS-CoV-2 vaccination (COVISHIELD) were recruited for the study. Blood samples were collected from participants at 3 time points; just before vaccination (Visit 0, V0), just before booster dose (Visit 1, V1) and 6th month after 1st dose (Visit 2, V2). Peripheral blood mononuclear cell isolation was done and evaluated for T and B cell subsets by Flow cytometry. Quantitative determination of IgG antibodies to SARS-CoV-2 was done by Chemiluminescence immunoassay in all samples. Final data for all three visits was available for 37 participants who remained healthy. Ethics approval was obtained from Medanta Institution of Ethics Committee vide MICR No. 1290/2021 dated 24th May 2021. RESULTS: Mean age of the participants was 34.6 â€‹± â€‹5.7 years (Range: 24-45 years). Highly significant improvement in SARS-CoV-2 IgG levels was observed after each visit {Mean IgG: (V0 v/s. V1: 133.8 â€‹± â€‹339.2AU/ml v/s. 434.5 â€‹± â€‹519.2AU/ml; p-value â€‹= â€‹0.003) and V0 v/s. V2: 133.8 â€‹± â€‹339.2AU/ml v/s. 420.9 â€‹± â€‹394.2AU/ml; p-value â€‹= â€‹0.002) Between visits 0 and 1, the mean value for CD4 Naïve T cells showed significant increase, while CD4 central memory (CM) T cells showed significant decrease. Between visits 0 and 2 the mean values for CD4 Naïve T cells, CD8 Naïve T cells and Pre germinal centre (Pre GC) B cells showed significant increase. During the same period the mean values for CD4CM, CD8 effector memory (EM) and CD8 CM T cells showed significant decrease. CONCLUSION: It is concluded that both, humoral and cellular immunity, play an important role in maintaining immunity against COVID-19 infection, following COVISHIELD vaccination. Moreover, in subjects with normalisation of antibody levels post vaccination, persistence of T cell subsets may still offer some immunity.