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1.
J Med Virol ; 94(5): 1906-1919, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34951021

RESUMEN

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induces the production of proinflammatory cytokines, which results in a cytokine storm, and immune-modulators like Mycobacterium indicus pranii (MIP) might ameliorate coronavirus disease of 2019 (COVID-19) related cytokine storm. Therefore, the present study evaluates whether MIP offers an advantage in the treatment of severe COVID-19 patients infected with SARS-CoV-2. A prospective MIP cohort study was conducted in chest disease hospitals in Srinagar, Jammu and Kashmir, India. In the present prospective, randomized clinical study, critically severe COVID-19 patients were divided into two groups, the MIP group (n = 105) and the best standard treatment (BST) group (n = 210). Procalcitonin, ferritin, high-sensitive C-reactive protein, D-dimer levels, and interleukin levels on 5th-day posttreatment were significantly reduced in the MIP group compared to the BST group. Compared to the BST group, 105 consecutive patients with severe COVID-19 in the MIP group reported early weaning off ventilation, resolution of chest architecture (computed tomography [CT] scan), a significant increase in SpO2 levels, and decreased mortality with a hazard ratio: 0.234 (95% confidence interval: 0.264-2.31) (p = 0.001). MIP restored SpO2 , immune/inflammatory response, normalized lung abnormalities (chest CT scan), and reduced mortality without any serious complications. However, there is a need for placebo-controlled double-blind and controlled clinical trials to confirm the efficacy.


Asunto(s)
COVID-19 , Estudios de Cohortes , Humanos , Mycobacterium , Estudios Prospectivos , SARS-CoV-2
2.
Medicina (Kaunas) ; 58(4)2022 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-35454373

RESUMEN

Background and Objectives: In women of reproductive age, leukocytosis is a risk factor that bridges low-grade chronic inflammation (metabolic inflammation), metabolic changes, and polycystic ovary syndrome (PCOS) and is a potential early predictor of PCOS. This study aims to explore the predictive role of quantitative changes in white blood cells (WBCs) and neutrophils in PCOS-associated metabolic changes. Materials and Methods: A total number of 176 blood samples were obtained from age-matched women of the reproductive period, comprising 88 PCOS cases and 88 healthy controls. Hematological, metabolic, and anthropometric indices and ultrasonic assessment were recorded. Results: Elevated levels of luteinizing hormone, testosterone, and lipid parameters except HDL-C levels, and the prevalence of metabolic syndrome in PCOS were statistically significant (p < 0.001). The neutrophil count and neutrophil−lymphocyte ratio (NLR) in PCOS patients were significantly higher (p < 0.001) than their counterparts. The predictive ability of the neutrophil count and neutrophil−lymphocyte ratio (NLR) for PCOS, and possibly its associating subclinical inflammation at optimum cut-off values for the neutrophil count and NLR of >46.62% (sensitivity 94.32% and specificity 74.42%) and >1.23 (sensitivity 71.59% and specificity 100%), respectively. With regard to the areas under the curve (AUC) and Youden indices, they constituted 0.922 and 0.697 for neutrophil count and 0.926 and 0.716 for NLR, respectively. The comparative ROC z-statistic value was 2.222 and a p = 0.026. The multiple linear regression analysis revealed no significant influence for hormonal and metabolic independent variables on the neutrophil count in PCOS cases, but, as can be expected, revealed a significant negative relationship with the other components of WBCs. Conclusion: In conclusion, relative neutrophilia and elevated NLR are potential cost-effective, sensitive, and specific predictors of PCOS that may also shed light on the mechanism of chronic low-grade inflammation that is characteristic of the disease.


Asunto(s)
Síndrome del Ovario Poliquístico , Estudios de Casos y Controles , Femenino , Humanos , Inflamación , Recuento de Leucocitos , Linfocitos , Neutrófilos , Síndrome del Ovario Poliquístico/complicaciones
3.
Curr Psychol ; : 1-8, 2022 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-35971337

RESUMEN

The dynamic nature of coronavirus-19 (Covid-19) has caused a wreaked havoc globally, with millions of confirmed cases and deaths. Therefore, it is important to understand the psychological impact of the Covid-19 on the patients. In the present study, we examine whether intolerance of uncertainty was related to the severity of symptoms and whether this relationship is mediated by perception of illness and covid-19 fear. The study sample comprised of 98 Covid-19 patients (Mean = 35.17 SD = 12.89). Mediation analysis was conducted using the PROCESS macro for SPSS. Results of mediation analysis showed that the direct effect of intolerance of uncertainty on symptom severity was insignificant. However, the indirect effect via illness perception was significant, reflecting full mediation. The findings add knowledge to our understanding of the psychological consequences of Covid-19. The present study has implications for mental health services for patients with Covid-19, which will play a vital role in recovery from the illness.

4.
Lung ; 196(4): 447-454, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29804144

RESUMEN

PURPOSE: Different mutations in coding and non-coding sequences of the SERPINA1 gene have been implicated in the pathogenesis of COPD. However, - 10T/C mutation in the hepatocyte-directed promoter region has not been associated with COPD pathogenesis so far. Here, we report an increased frequency of - 10C genotype that is associated with decreased levels of serum alpha1-antitrypsin (α1AT) in COPD patients. METHODS: The quantification of serum α1AT was done by ELISA, the phenol-chloroform method was used for DNA extraction, PCR products were directly sequenced. The IBM SPSS Statistics v21 software was used for statistical analyses of the data. RESULTS: The mean serum α1AT level was found to be 1.203+0.239 and 3.162+0.160 g/L in COPD cases and in control, respectively. The - 10C allele is associated with an increased risk of COPD [OR, 3.50 (95%CI, 1.86-6.58); p < 0.001]. The combined variant genotype (TT+CC) was significantly found associated with an increased risk of COPD [OR, 3.20 (95% CI, 1.47-6.96); p = 0.003]. A significant association of the family history with COPD (overall p value= 0.0331) suggests that genetics may play an important role in the pathogenesis of COPD. CONCLUSION: The polymorphism associated with hepatocyte-specific promoter region (- 10T/C) is likely to be associated with the pathogenesis of COPD. It is quite possible that the change of the base in the hepatocyte-specific promoter of the SERPINA1 gene can modulate its strength, thereby driving the reduced expression of α1AT.


Asunto(s)
Hepatocitos/enzimología , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Enfermedad Pulmonar Obstructiva Crónica/genética , alfa 1-Antitripsina/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , India/epidemiología , Masculino , Fenotipo , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/enzimología , Enfermedad Pulmonar Obstructiva Crónica/etnología , Factores de Riesgo , alfa 1-Antitripsina/sangre
5.
Infect Disord Drug Targets ; 23(2): e280922209238, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36173061

RESUMEN

PURPOSE: The antimicrobial prescription in urinary tract infections (UTI) is driven by local data on its pathogenic spectrum and the resistance pattern exhibited by the disease-causing pathogens. We aimed to determine the bacteriological diversity of UTI causing pathogens and antimicrobial resistance in mostly gram-negative bacteria. METHODS: This retrospective hospital-based cross-sectional study analyzed the culture and sensitivity reports of urine samples from a referral centre in the Aljouf region of Saudi Arabia. All the antibiograms from January 1, 2020, to December 31st 2020, were included. The bacterial identification and antimicrobial testing were carried out by the BD Phoenix system (BD Diagnostics, Sparks, MD, USA). Antimicrobial testing was performed as per the Clinical and Laboratory Standard Institute recommendations. Frequencies of multidrug- and extensive drug resistance were calculated. RESULTS: Of the 1334 non-duplicate urine samples received, 422 (31.6%) bacterial growths were observed. Of these, 383 (90.8%) and 39 (9.2%) were gram-negative and gram-positive bacterial isolations, respectively. E. coli 161 (38.1%), K. pneumoniae 97 (23.0%), and E. faecalis 18 (4.3%) were frequent aetiologies of UTI. 309 (80.7%) of gram-negative bacteria were multidrug-resistant including 88 (23.0%) extensively drug-resistant. Overall, a resistance rate of > 55 % to 1st through 4th generation cephalosporins was observed except for cefoxitin (43.7%). A resistance rate of 37.6% was observed towards carbapenems, with the lowest rate (34.0%) to meropenem. CONCLUSION: Multi-drug resistant gram-negative bacteria dominate the pathogenic spectrum of UTI in the region. A high resistance rate to cephalosporins and carbapenems exists in gram-negative organisms, causing UTI.


Asunto(s)
Antiinfecciosos , Infecciones Urinarias , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Escherichia coli , Estudios Transversales , Estudios Retrospectivos , Infecciones Urinarias/microbiología , Bacterias Gramnegativas , Carbapenémicos , Cefalosporinas , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana
6.
Trop Med Infect Dis ; 8(6)2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37368744

RESUMEN

The treatment and outcome of respiratory virus infections differ. SARS-CoV-2, as well as other respiratory viruses such as influenza virus (A and B) and respiratory syncytial virus (RSV), require simultaneous, cost-effective, and rapid differential detection. We used a gold standard five-target single-step RT-PCR to detect influenza viruses, RSV, and SARS-CoV-2, and this method can be extended to detect influenza virus subtypes. As a result, this five-target single-step RT-PCR method is ideal for differentiating respiratory viruses. The 5' nuclease activity of Taq DNA polymerase is used in the real-time reverse transcription PCR assay. The Taq man fast viral 1-step enzyme is a 4× Master mix and five-target primer probe mix that detects influenza A, influenza B, SARS-CoV-2 ORF1ab, respiratory syncytial viruses A/B and actin. When compared with TaqMan TM and Invitrogen superscript TM III Platinum and the Meril Kit for SARS-CoV-2, the assay demonstrated 100% sensitivity, specificity, and amplification efficiency of 90.1% for target genes. In conclusion, our one-tube multiplex RT-PCR assay offers a rapid and reliable method for the simultaneous detection of influenza A/B, RSV, and SARS-CoV-2 from nasopharyngeal swabs. This assay has the potential to enhance diagnostic capabilities and improve public health responses during respiratory outbreaks, enabling timely interventions and informed decision making.

7.
Healthcare (Basel) ; 11(3)2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36766892

RESUMEN

BACKGROUND: For centuries, convalescent plasma (CP) has been recommended to treat a diverse set of viral diseases. Therefore, the present study was undertaken to evaluate the effectiveness of CP in critically ill COVID-19 patients. METHODS AND MATERIALS: From 23 March 2021 to 29 December 2021, an open-label, prospective cohort, single-centre study was conducted at Chest Disease Hospital, Jammu and Kashmir, Srinagar. Patients with severe manifestation of coronavirus disease 2019 (COVID-19) under BST (best standard treatment) +CP were prospectively observed in order to evaluate effectiveness of CP therapy and historical control under BST were used as the control group Results: A total of 1667 patients were found positive for COVID-19. Of these, 873 (52.4%), 431 (28.8%), and 363 (21.8%) were moderately, severely, and critically ill, respectively. On 35th day post-infusion of CP, all-cause mortality was higher in the BST (best standard treatment) +CP group 12 (37.5%) compared to 127 (35%) in the BST group with an odds ratio (OR) of 1.4 and hazard ratio (HR) (95% CI: 1.08-1.79, p = 0.06). Similarly, 7 (21.9) patients in the BST+CP group and 121 (33.3) patients in the BST group showed the transition from critically ill to moderate disease with subhazard ratio (s-HR 1.37) (95% CI: 1.03-2.9). CONCLUSIONS: In the present study, we could not find any significant difference in the CP group and BST +CP in primary outcome of reducing all-cause mortality in critically ill patients with negligible Nabs levels. However, beneficial results were observed with use of CP in a limited number of secondary outcomes which includes days of hospitalization, negative conversion of SARS-CoV-2 on basis of RT-PCR on 7th day and 14th day, need for invasive mechanical ventilation on 14th day post-CP treatment, and resolution of shortness of breath.

8.
Healthcare (Basel) ; 11(7)2023 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-37046870

RESUMEN

The present study evaluated the clinical presentation and outcome of COVID-19 patients with underlying hypercreatinemia at the time of hospitalization. A retrospective observational study was conducted from the 23rd of March 2020 to the 15th of April 2021 in 1668 patients confirmed positive for COVID-19 in the Chest Disease Hospital in Srinagar, India. The results of the present study revealed that out of 1668 patients, 339 with hypercreatinemia had significantly higher rates of admission to the intensive care unit (ICU), severe manifestations of the disease, need for mechanical ventilation, and all-cause mortality. Multivariable analysis revealed that age, elevated creatinine concentrations, IL-1, D-Dimer, and Hs-Crp were independent risk factors for in-hospital mortality. After adjusted analysis, the association of creatinine levels remained strongly predictive of all-cause, in-hospital mortality (HR-5.34; CI-4.89-8.17; p ≤ 0.001). The amelioration of kidney function may be an effective method for achieving creatinemic targets and, henceforth, might be beneficial for improving outcomes in patients with COVID-19.

9.
J Family Med Prim Care ; 11(4): 1519-1524, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35516702

RESUMEN

Aim: To study the impact of age, gender and comorbidities/risk factors affecting the severity of CoronaVirus Disease 2019/Severe acute respiratory syndrome coronavirus 2 (COVID-19/SARS-COV-2) infection in the Kashmiri community. Materials and Methods: The present descriptive cross-sectional study was conducted in the Chest Disease Hospital. The study included 957 subjects who were diagnosed with SARS-CoV-2 infection. Descriptive statistics were calculated. Results: In the age group <40 years, the severity of illness was found to be 30.42% and the occurrence of death was 11.54%, in the 40-60 years, the severity of the illness was found to be 32.51% and the occurrence of death was 12.84%, in the older age >60 years, the severity of illness was found to be 35.74% and the occurrence of death was 10.49%. In males, the severity of the illness was found to be 32.39% and the occurrence of death was 11.27%. In females, the severity of the illness was found to be 33.96% and the occurrence of death was 12.58%. In patients suffering from chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus, coronary artery disease (CAD), chronic kidney disease (CKD), cancer, hypertension, chronic liver disease (CLD), cerebrovascular disease, thyroid disease, steroid use, obstructive sleep apnoea (OSA) and smokers, the severity of the illness was 29.27, 41.67, 37.73, 20, 23.53, 11.11, 36.30, 40, 20, 36.37, 50, 54.54 and 36% and the occurrence of death was 14.63, 0, 10.69, 10, 11.76, 5.55, 10.67, 0, 0, 20.78, 0, 0 and 16%, respectively. Conclusion: The age, gender and comorbidity disparities seen in the COVID-19 vulnerability emphasise the need to understand the impact of these factors on the incidence and case fatality of the disease.

10.
J Family Med Prim Care ; 11(3): 982-986, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35495815

RESUMEN

Background: Due to an enormous health care crisis arising out of COVID-19 pandemic, alternate methods of seeking treatment like tele-consultation proved useful to patients. We assessed the role of teleconsultation in managing COPD exacerbations at home in the times of COVID-19 crisis. Materials and Methods: A prospective study of 527 diagnosed cases of COPD seeking treatment for exacerbation of their illness telephonically because of difficulty in visiting the hospitals created by the COVID-19 lockdown. Data were collected telephonically and via social media platforms from April 7,2020 to October 29, 2020.The patients were treated for exacerbation and followed telephonically at day 3,5,7, 14 and day 30. Patients who turned to be COVID-19 positive were referred to COVID health facility centers. Results: 509 patients out of 527 patients were treated for exacerbation of COPD, 18 patients tested positive for COVID-19. Out of 509, 13 patients did not improve and had to be referred to hospital. All of them had acute respiratory failure (Type 2) as documented by their arterial blood gas analysis. 2 out of them did not survive. 496 out of 509 (97.4%) patients of COPD exacerbation were successfully treated via teleconsultations and with a follow-up of 4 weeks period minimum for all the patients. Conclusion: Teleconsultation provided excellent means to manage COPD exacerbation remotely with equally effective outcome as seen in hospital care in the times of health care crises due to COVID-19 pandemic.

11.
Indian J Otolaryngol Head Neck Surg ; 74(Suppl 2): 2772-2779, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33134156

RESUMEN

Aim and Objectives: To describe the prevalence and characteristics of olfactory dysfunction (OD) in patients with laboratory-confirmed COVID-19 infection. Materials and Methods: This monocentric study was performed at Chest Diseases Hospital during the COVID-19 pandemic and all patients testing positive for COVID-19 over a 5-month period (April to August 2020) were recruited. Detailed history was elicited from subjects and all patients were inquired about olfactory dysfunction (OD). Patients with olfactory dysfunction were asked to complete olfactory questionnaires based on the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). Results: 655 patients with mild to moderate COVID-19 infection were included in the study. The prevalence rate of olfactory dysfunction was 18.47% (n = 121) with contribution of 11.60% (n = 76) and 6.87% (n = 45) from anosmia and hyposmia respectively, thereby suggesting olfactory dysfunction to be a significant clinical feature in COVID-19 patients. Males were significantly more affected by olfactory dysfunctions than females. Anosmic patients had significantly reduced sQOD-NS results as compared to hyposmic patients (significant at P < 0.05). The mean duration of OD was 7.7 days (± 4.3) and >90% patients in our study showed resolution within 14 days. Conclusion: The early recognition of olfactory dysfunction should help to screen, identify and thereby quickly isolate mildly symptomatic COVID-19 patients from the general population and the existence of these dysfunctions may well be a prognostic factor in the course of the disease.

12.
Biomed Rep ; 17(6): 94, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36382262

RESUMEN

The aim of the present study was to investigate the clinical features and laboratory parameters of hospitalized patients with coronavirus disease 2019 (COVID-19) and assess the characteristics between severe and non-severe cases. The study retrospectively analyzed the clinical data of 1,096 patients, of which, 626 (57.11%) and 470 (42.89%) were categorized into severe and non-severe groups, respectively. Clinical parameters such as signs and symptoms, comorbidities, levels of D-dimer, C-reactive protein (CRP), interleukin 6 (IL-6) and lactate dehydrogenase were analyzed. The data are presented as frequencies, means and standard deviations. The chi-square test and Mann-Whitney U test were used to assess any significant differences between the severe and non-severe COVID-19 groups. The clinical symptoms in severe COVID-19 cases included anosmia (P≤0.01), sore throat (P≤0.01), fatigue (P≤0.01), headache (P≤0.01), and shortness of breath (P≤0.01). Laboratory findings showed a significant increase in CRP (21.90±40.23 vs. 16.13±21.82; P≤0.01) and IL-6 levels (58.92±55.07 vs. 41.41±38.30; P≤0.01). Patients with severe COVID-19 had significant lymphopenia compared with that in non-severe cases. Among the comorbidities, hypertension (P≤0.01) was significantly more frequent in patients with severe COVID-19. In conclusion, major derangements in laboratory parameters were observed in patients with severe COVID-19 infection.

13.
Diagnostics (Basel) ; 12(7)2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35885514

RESUMEN

Lung cancer is the dominant emerging factor in cancer-related mortality around the globe. Therapeutic interventions for lung cancer are not up to par, mainly due to reoccurrence/relapse, chemoresistance, and late diagnosis. People are currently interested in miRNAs, which are small double-stranded (20-24 ribonucleotides) structures that regulate molecular targets (tumor suppressors, oncogenes) involved in tumorigeneses such as cell proliferation, apoptosis, metastasis, and angiogenesis via post-transcriptional regulation of mRNA. Many studies suggest the emerging role of miRNAs in lung cancer diagnostics, prognostics, and therapeutics. Therefore, it is necessary to intensely explore the miRNOME expression of lung tumors and the development of anti-cancer strategies. The current review focuses on the therapeutic, diagnostic, and prognostic potential of numerous miRNAs in lung cancer.

14.
J Educ Health Promot ; 11: 73, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35372602

RESUMEN

BACKGROUND: The World Health Organization declared vaccine hesitancy as one of the planet's top 10 global health threats in 2019. With the rollout of the coronavirus disease-19 (COVID-19) vaccines, a survey was conducted to find out the hesitancy and the apprehensions that come along with taking COVID-19 vaccines among health-care workers (HCWs). MATERIALS AND METHODS: This was an online cross-sectional survey which was developed and shared through social media platforms among the HCWs of Kashmir. The survey captured demographic data and used a validated hesitancy measurement tool from January 2021 to February 2021. The data were analyzed by descriptive statistics and multivariable logistic regression using Stata 15 (Stata Corp. 2017. Stata Statistical Software: Release 15. College Station, TX: Stata Corp LLC). RESULTS: Willingness to take the COVID-19 vaccine when available was seen in 67.7% of the HCWs. Overall, 9.59% of respondents reported unwillingness to receive a vaccine for COVID-19, while 22.7% were unsure. The most commonly cited reason for willingness to get vaccinated was an understanding of the disease and vaccination, as reported by 81.5%. Being single was significantly related to an increased risk of vaccine hesitancy (adjusted odds ratio = 5.27, 95% confidence interval: 2.07-13.40). Among vaccine attitudes, concerns about the safety of the vaccine, unforeseen problems in children, and possible unknown future adverse effects of the vaccine were the most important determinants of unwillingness. CONCLUSIONS: A significant proportion of the HCWs showed vaccine hesitancy to the COVID-19 vaccine. Hesitancy attitudes were almost always driven by concern around the vaccine safety. States and health-care authorities need to recognize the massive trust deficit around the Covid-19 vaccine and use the popular media used by people to share credible and reliable information.

15.
J Educ Health Promot ; 11: 59, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35372617

RESUMEN

BACKGROUND: Vaccine hesitancy is seen, globally, as a major factor that will determine future coronavirus disease-19 (COVID-19) spread and its effective management. This study aimed to identify COVID-19 vaccine perception, acceptance, confidence, hesitancy, and barriers among the general population. MATERIALS AND METHODS: This was an online survey which was developed and shared through social media platforms among the general population of Kashmir. The survey captured demographic data and used a validated hesitancy measurement tool. We analyzed the data using descriptive statistics and multivariable logistic regression using Stata 15 (Stata Corp. 2017. Stata Statistical Software: Release 15. College Station, TX, USA: Stata Corp LLC). RESULTS: A total of 835 responses were received. Most participants were males, with females compromising of 19.5% participants. 65.1% of participants were in the age group of 30-50, whereas 19.2% were below 30 years of age. 52.70% of respondents were willing to take the vaccine when available, while 32.5% of respondents were unsure about their decision of inoculation. The most cited reason for willingness to get vaccinated was an understanding of the disease and vaccination. 41.70% felt that the vaccines developed against COVID-19 have not been fully tested; therefore, concerns around the safety and its longer-term side effects were the reasons cited. Public health messaging should be tailored to address these concerns. CONCLUSIONS: Vaccine hesitancy is a global threat undermining the control of preventable infections. The government should take proactive steps to address the factors that may potentially impact the benefits expected from the introduction of a COVID-19 vaccine in the union territory.

16.
J Biomol Struct Dyn ; 40(22): 12037-12047, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34431457

RESUMEN

Dep domain containing mTOR interacting protein (DEPTOR) has critical implications in the development and progression of human malignancies. Increased expression of DEPTOR promotes the growth of tumor cells by inhibiting the mTORC1, which alleviates the negative feedback inhibition by mTORC1 downstream target S6Ks on PI3K/AKT pathway thereby promotes cell survival and prevents apoptosis. This clearly suggests that targetting DEPTOR-mTOR interactions through small molecules may prove as an effective strategy for circumventing distinct cancers. In this study, we employed a top-down approach for finding three novel molecules which may prove effective in disrupting Deptor-mTOR interaction. Following DEPTOR modelling and validation we performed grid-directed structure-based screening by specifying the residues of DEPTOR known to interact with mTOR. A library of 10,000 protein-protein disrupting molecules was screened against the defined region of DEPTOR. From the screened molecules, 30 molecules with highest binding affinity were chosen for molecular docking. Thirty (30) extra-precision molecular docking experiments and 30 molecular mechanics generalized born surface area (MMGBSA) assays were performed. Following this top 10 molecules in terms of binding affinity were selected and the interaction profile of their corresponding docked files was generated. The top three molecules were finally selected after taking all the three parameters including docking score, binding energy value and interaction profile into consideration. For atomistic insights regarding DEPTOR-topmost hit interactions, molecular dynamics was performed for 100 ns. This molecule after further evaluation may prove as promising candidate for anticancer therapy.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Simulación de Dinámica Molecular , Fosfatidilinositol 3-Quinasas , Humanos , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas/metabolismo , Péptidos y Proteínas de Señalización Intracelular , Serina-Treonina Quinasas TOR/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo
17.
J Infect Public Health ; 15(11): 1299-1314, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36279686

RESUMEN

As of 25th July, 2022, global Disease burden of 575,430,244 confirmed cases and over 6,403,511 deaths have been attributed to coronavirus disease 2019 (COVID-19). Co-infections/secondary infections continue to plague patients around the world as result of the co-morbidities like diabetes mellitus, biochemical changes caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) especially significant elevation in free iron levels, immune suppression caused by SARS-CoV-2, and indiscriminate use of systemic corticosteroids for the treatment of severe COVID-19 disease. In such circumstances, opportunistic fungal infections pose significant challenge for COVID-19 disease therapy in patients with other co-morbidities. Although COVID-19-associated Mucormycosis (CAM) has been widely recognized, currently extensive research is being conducted on mucormycosis. It has been widely agreed that patients undergoing corticosteroid therapy are highly susceptible for CAM, henceforth high index of screening and intensive care and management is need of an hour in order to have favorable outcomes in these patients. Diagnosis in such cases is often delayed and eventually the disease progresses quickly which poses added burden to clinician and increases patient load in critical care units of hospitals. A vast perusal of literature indicated that patients with diabetes mellitus and those with other co-morbidities might be highly vulnerable to develop mucormycosis. In the present work, the case series of three patients presented at Chest Disease Hospital Srinagar, Jammu and Kashmir infected with CAM has been described with their epidemiological data in supplementary section. All these cases were found to be affected with co-morbidity of Diabetes Mellitus (DM) and were under corticosteroid therapy. Furthermore, given the significant death rate linked with mucormycosis and the growing understanding of the diseases significance, systematic review of the literature on CAM has been discussed and we have attempted to discuss emerging CAM and related aspects of the disease.


Asunto(s)
COVID-19 , Coinfección , Diabetes Mellitus , Mucormicosis , Humanos , Mucormicosis/tratamiento farmacológico , Mucormicosis/epidemiología , SARS-CoV-2 , Diabetes Mellitus/epidemiología , Corticoesteroides/uso terapéutico
18.
Basic Clin Pharmacol Toxicol ; 129(2): 104-129, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33977663

RESUMEN

BACKGROUND: The COVID-19 pandemic has demanded effective therapeutic protocol from researchers and clinicians across the world. Currently, a large amount of primary data have been generated from several preclinical studies. At least 300 clinical trials are underway for drug repurposing against COVID-19; the clinician needs objective evidence-based medication to treat COVID-19. OBSERVATIONS: Single-stranded RNA viral genome of SARS-CoV-2 encodes structural proteins (spike protein), non-structural enzymatic proteins (RNA-dependent RNA polymerase, helicase, papain-like protease, 3-chymotrypsin-like protease) and other accessory proteins. These four enzymatic proteins on spike protein are rate-limiting steps in viral replications and, therefore, an attractive target for drug development against SARS-CoV-2. In silico and in vitro studies have identified various potential epitomes as candidate sequences for vaccine development. These studies have also revealed potential targets for drug development and drug repurposing against COVID-19. Clinical trials utilizing antiviral drugs and other drugs have given inconclusive results regarding their clinical efficacy and side effects. The need for angiotensin-converting enzyme (ACE-2) inhibitors/angiotensin receptor blockers and corticosteroids has been recommended. Western countries have adopted telemedicine as an alternative to prevent transmission of infection in the population. Currently, no proven, evidence-based therapeutic regimen exists for COVID-19. CONCLUSION: The COVID-19 pandemic has put tremendous pressure on researchers to evaluate and approve drugs effective against the disease. Well-controlled randomized trials should assess medicines that are not marketed with substantial evidence of safety and efficacy and more emphasis on time tested approaches for drug evaluation.


Asunto(s)
Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Reposicionamiento de Medicamentos , COVID-19/epidemiología , COVID-19/virología , Simulación por Computador , Humanos , Pandemias , SARS-CoV-2/efectos de los fármacos
19.
Diagnostics (Basel) ; 11(2)2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33578944

RESUMEN

Lung cancer is a well-known malignant tumor of the respiratory tract, which has caused a significant level of damage to human health in the 21st century. Micro-RNAs (miRNAs) are tiny, non-coding RNA stem-loop structures with a length of roughly 20-25 nucleotides that function as powerful modulators of mRNA and protein products of a gene. miRNAs may modulate many biological processes involving growth, differentiation, proliferation, and cell death and play a key role in the pathogenesis of various types of malignancies. Several accumulating pieces of evidence have proven that miRNA, especially miR-146a, are crucial modulators of innate immune response sequences. A novel and exciting cancer research field has involved miRNA for the detection and suppression of cancer. However, the actual mechanism which is adopted by these miRNA is still unclear. miRNAs have been used as a cancer-associated biomarker in several studies, suggesting their altered expression in various cancers compared to the normal cells. The amount of expression of miRNA can also be used to determine the stage of the disease, aiding in early detection. In breast, pancreatic, and hepatocellular carcinoma, and gastric cancer, cancer cell proliferation and metastasis has been suppressed by miR-146a. Changes in miR-146a expression levels have biomarker importance and possess a high potential as a therapeutic target in lung cancer. It retards epithelial-mesenchymal transition and promotes the therapeutic action of anticancer agents in lung cancer. Studies have also suggested that miR-146a affects gene expression through different signaling pathways viz. TNF-α, NF-κB and MEK-1/2, and JNK-1/2. Further research is required for understanding the molecular mechanisms of miR-146a in lung cancer. The potential role of miR-146a as a diagnostic marker of lung cancer must also be analyzed. This review summarizes the tumor-suppressing, anti-inflammatory, and antichemoresistive nature of miR-146a in lung cancer.

20.
J Educ Health Promot ; 10: 309, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34667809

RESUMEN

BACKGROUND: The coronavirus disease-19 (COVID-19) emerged from China and rapidly spread to many other countries all over the world. This study aimed to assess the prevalence of anxiety, depression, posttraumatic stress disorder, and obsessive-compulsive (OC) symptoms among COVID-19 survivors after their discharge from the COVID-19 treatment center. MATERIALS AND METHODS: This was a cross-sectional, hospital-based study performed among 119 COVID-19 survivors. The Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety and depression. Posttraumatic Stress Disorder (PTSD)-Checklist (PCL) and Brief OC Scale were used to measure PTSD and OC symptoms. Data were analyzed by descriptive and inferential statistics using the SPSS (IBM Corp. Released 2015 version 23.0). RESULTS: The mean anxiety, depression, and PTSD scores were, 7.12 ± 0.68, 8.08 ± 0.22, and 19.78 ± 0.88, respectively. Based on cutoff scores, the prevalence of anxiety, depression, and PTSD among COVID-19 survivors was n = 53, 44.54%; n = 73, 61.34%; and n = 30, 25.21%, respectively. Older COVID-19 survivors (≥50 years) were more likely to show symptoms of depression and anxiety (P < 0.001) compared to younger ones. Furthermore, COVID-19 survivors who were ≥50 years of age experienced a greater level of PTSD compared to younger ones; similar trends were seen in those experiencing OC symptoms. In the present study, n = 98 (82.4%) were obsessed with fears of contamination and an equal number had compulsive handwashing. CONCLUSION: Anxiety, depression, PTSD, and OC symptoms are common among the COVID-19 survivors and that underscores the need to diagnose and manage mental health morbidities among these survivors long after their recovery from COVID-19.

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