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1.
FASEB J ; 38(3): e23461, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38317639

RESUMO

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.


Assuntos
Esclerose Lateral Amiotrófica , Superóxido Dismutase-1 , Animais , Camundongos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Modelos Animais de Doenças , Camundongos Transgênicos , Células Musculares/metabolismo , Mutação , Superóxido Dismutase-1/genética
2.
Mol Cell Biochem ; 479(1): 127-170, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37016182

RESUMO

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.


Assuntos
Exossomos , Neoplasias Meníngeas , Meningioma , Humanos , Exossomos/metabolismo , Meningioma/tratamento farmacológico , Meningioma/metabolismo , Relevância Clínica , Sistemas de Liberação de Medicamentos , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/metabolismo
3.
Mol Cell Biochem ; 478(1): 69-88, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35725992

RESUMO

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.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/efeitos adversos , Metotrexato/uso terapêutico , Glucocorticoides/uso terapêutico , Quimioterapia Combinada
4.
Mol Cell Biochem ; 478(1): 149-160, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35750979

RESUMO

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.


Assuntos
COVID-19 , Diabetes Mellitus , Hipertensão , Insuficiência Renal Crônica , Feminino , Humanos , Masculino , Idoso , COVID-19/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Fatores de Risco , Diabetes Mellitus/epidemiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Insuficiência Renal Crônica/epidemiologia
5.
Indian J Med Res ; 157(4): 293-303, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37102510

RESUMO

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.


Assuntos
COVID-19 , Ingredientes de Alimentos , Humanos , Nutrigenômica , Dióxido de Carbono , Lipopolissacarídeos , Pandemias , Síndrome da Liberação de Citocina , Ácido Palmítico , SARS-CoV-2 , Dieta/métodos , Comportamento Alimentar , Zinco , Chá , Ferro , Triglicerídeos
6.
Crit Rev Clin Lab Sci ; 59(7): 445-459, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35289222

RESUMO

A plethora of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic tests are available, each with different performance specifications, detection methods, and targets. This narrative review aims to summarize the diagnostic technologies available and how they are best selected to tackle SARS-CoV-2 infection as the pandemic evolves. Seven key settings have been identified where diagnostic tests are being deployed: symptomatic individuals presenting for diagnostic testing and/or treatment of COVID-19 symptoms; asymptomatic individuals accessing healthcare for planned non-COVID-19-related reasons; patients needing to access emergency care (symptom status unknown); patients being discharged from healthcare following hospitalization for COVID-19; healthy individuals in both single event settings (e.g. airports, restaurants, hotels, concerts, and sporting events) and repeat access settings (e.g. workplaces, schools, and universities); and vaccinated individuals. While molecular diagnostics remain central to SARS-CoV-2 testing strategies, we have offered some discussion on the considerations for when other tools and technologies may be useful, when centralized/point-of-care testing is appropriate, and how the various additional diagnostics can be deployed in differently resourced settings. As the pandemic evolves, molecular testing remains important for definitive diagnosis, but increasingly widespread point-of-care testing is essential to the re-opening of society.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Teste para COVID-19 , COVID-19/diagnóstico , Pandemias , Testes Imediatos , Sensibilidade e Especificidade
7.
Mol Cell Biochem ; 477(3): 815-832, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35059925

RESUMO

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.


Assuntos
Vírus da Dengue/metabolismo , Dengue/sangue , Exossomos/metabolismo , Aedes/virologia , Animais , Biomarcadores/sangue , Dengue/diagnóstico , Dengue/transmissão , Humanos , Mosquitos Vetores/virologia , Prognóstico
8.
J Infect Dis ; 224(12 Suppl 2): S710-S716, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34550374

RESUMO

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.


Assuntos
Cólera/epidemiologia , Cólera/prevenção & controle , Doenças Endêmicas , Vacinação , Cólera/transmissão , Vacinas contra Cólera , Surtos de Doenças , Humanos , Índia/epidemiologia , Vigilância da População , Saúde Pública
9.
Mol Biol Rep ; 48(12): 8061-8074, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34687392

RESUMO

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.


Assuntos
Vesículas Extracelulares/metabolismo , Meningioma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Sistemas de Liberação de Medicamentos/métodos , Exossomos/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/fisiologia , Humanos , Biópsia Líquida/métodos , Meningioma/tratamento farmacológico , Meningioma/genética , Gradação de Tumores/métodos , Prognóstico , Proteômica/métodos , Tetraspaninas/metabolismo
10.
Indian J Med Res ; 154(6): 843-848, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-35662089

RESUMO

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.


Assuntos
Linfo-Histiocitose Hemofagocítica , Adolescente , Adulto , Biomarcadores , Criança , Pré-Escolar , Humanos , Índia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Receptores de Interleucina-2 , Valores de Referência
11.
Pancreatology ; 19(8): 1034-1042, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31668563

RESUMO

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.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Neurais/transplante , Neoplasias Pancreáticas/terapia , Microambiente Tumoral , Animais , Humanos
12.
J Assoc Physicians India ; 67(4): 71-73, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31309802

RESUMO

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.


Assuntos
Inteligência Artificial , Aprendizado Profundo , Atenção à Saúde , Algoritmos , Diabetes Mellitus Tipo 2 , Humanos , Médicos
13.
J Infect Dis ; 218(suppl_4): S206-S213, 2018 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-30307566

RESUMO

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.


Assuntos
Salmonella paratyphi A/efeitos dos fármacos , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos , Criança , Pré-Escolar , Estudos Transversais , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Hospitais , Humanos , Índia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/imunologia , Adulto Jovem
16.
Natl Med J India ; 27(2): 70-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25471757

RESUMO

BACKGROUND: Rheumatic fever (RF)/rheumatic heart disease (RHD) continue to be a neglected public health priority. We carried out a registry-based control project, prospective surveillance and sample surveys to estimate the burden of disease. METHODS: We trained healthcare providers and established a surveillance system for the 1.1 million population of Rupnagar district in Punjab. In sample surveys conducted among schools, physicians examined the sampled children. Children with a cardiac murmur were investigated by echocardiography. Throat swabs were obtained from a sub-sample, and group A streptococci (GAS) were identified and emm typed by standard laboratory methods. We estimated the morbidity rates for RF/RHD from surveillance data and school surveys using a correction factor to account for under-registration of cases in the registry. RESULTS: A total of 813 RF/RHD cases were registered from 2002 to 2009. Of the 203 RF and 610 RHD cases, respectively, 51.2% and 36.7% were males. In the age group of 5-14 years, RF was more common (80%) than RHD (27%). The prevalence of RF/RHD in 5-14-year-old students was 1.0/1000 (95% CI 0.8-1.3). The school survey indicated that about two-thirds of the RF/RHD cases were enrolled in the hospital-based registries. Based on the school survey, the prevalence of RF/RHD was estimated to be 143/100,000 population. In the registry, the annual incidence of acute RF was estimated to be at least 8.7/100 000 children in the age group of 5-14 years. The prevalence of GAS was 2% (13/656) in children with sore throat and 0.5% (14/2920) among those not having sore throat. Typing of 27 GAS revealed 16 emm types. We estimate that about 1000 episodes of GAS pharyngitis lead to one episode of acute RF. CONCLUSION: RF/RHD continue to be a public health problem in Punjab, India.


Assuntos
Faringite/epidemiologia , Faringite/microbiologia , Febre Reumática/epidemiologia , Febre Reumática/microbiologia , Cardiopatia Reumática/epidemiologia , Cardiopatia Reumática/microbiologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Adolescente , Criança , Pré-Escolar , Ecocardiografia , Feminino , Humanos , Incidência , Índia/epidemiologia , Masculino , Vigilância da População , Prevalência , Estudos Prospectivos , Sistema de Registros
17.
Int J Surg ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38377059

RESUMO

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.

18.
Respir Med ; 231: 107716, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914209

RESUMO

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.

19.
Front Pharmacol ; 14: 1125305, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969857

RESUMO

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.

20.
Microbiol Res ; 277: 127504, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37812873

RESUMO

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.


Assuntos
Mpox , Óleos Voláteis , Animais , Humanos , Mpox/epidemiologia , Mpox/prevenção & controle , Surtos de Doenças/prevenção & controle , Saúde Pública , África
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