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1.
Front Cell Infect Microbiol ; 11: 648903, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33842396

RESUMO

As India moves toward the elimination of visceral leishmaniasis (VL) as a public health problem, comprehensive timely case detection has become increasingly important, in order to reduce the period of infectivity and control outbreaks. During the 2000s, localized research studies suggested that a large percentage of VL cases were never reported in government data. However, assessments conducted from 2013 to 2015 indicated that 85% or more of confirmed cases were eventually captured and reported in surveillance data, albeit with significant delays before diagnosis. Based on methods developed during these assessments, the CARE India team evolved new strategies for active case detection (ACD), applicable at large scale while being sufficiently effective in reducing time to diagnosis. Active case searches are triggered by the report of a confirmed VL case, and comprise two major search mechanisms: 1) case identification based on the index case's knowledge of other known VL cases and searches in nearby houses (snowballing); and 2) sustained contact over time with a range of private providers, both formal and informal. Simultaneously, house-to-house searches were conducted in 142 villages of 47 blocks during this period. We analyzed data from 5030 VL patients reported in Bihar from January 2018 through July 2019. Of these 3033 were detected passively and 1997 via ACD (15 (0.8%) via house-to-house and 1982 (99.2%) by light touch ACD methods). We constructed multinomial logistic regression models comparing time intervals to diagnosis (30-59, 60-89 and ≥90 days with <30 days as the referent). ACD and younger age were associated with shorter time to diagnosis, while male sex and HIV infection were associated with longer illness durations. The advantage of ACD over PCD was more marked for longer illness durations: the adjusted odds ratios for having illness durations of 30-59, 60-89 and >=90 days compared to the referent of <30 days for ACD vs PCD were 0.88, 0.56 and 0.42 respectively. These ACD strategies not only reduce time to diagnosis, and thus risk of transmission, but also ensure that there is a double check on the proportion of cases actually getting captured. Such a process can supplement passive case detection efforts that must go on, possibly perpetually, even after elimination as a public health problem is achieved.

2.
Nucl Med Commun ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33795613

RESUMO

BACKGROUND: For the response assessment after chemotherapy, gold standard is always the histopathological response. However, metabolic response can also guide further treatment. Herein, this study aimed to evaluate metabolic response assessment to neoadjuvant chemotherapy in squamous cell carcinoma esophagus using PET response criteria in solid tumors (PERCIST) criteria with taking histopathological response by tumor regression grading as the standard method. METHODS: Total fifty-seven patients with squamous cell carcinoma esophagus were enrolled between April 2017 to December 2018 for this prospective study. All patients were undergone for baseline PET scan before going for neoadjuvant chemotherapy. Repeat PET scan was done after neoadjuvant chemotherapy. Operable patients were taken for surgery. Final histological response was assessed by Mandard grading. Three metabolic tools [maximum standardized uptake value (SUVmax), tumor regression grading, PERCIST] were compared. RESULTS: The mean SULpeak of the primary lesion was 11.7 ± 5.5 (median, 10.2, range 5.5-31.8). The average percentage change (%Δ) in SUVmax was 42.9 ± 26.3. On histopathology, 5 (13.1%) patients showed complete pathological response, whereas grade II, III, IV and V in 8 (21.1%), 12 (31.6%), 10 (26.3%) and 3 (7.8%) respectively. On comparison of PERCIST with Mandard grading, agreement analysis showed that there was moderate agreement (k, 0.48). %ΔSUV peak change showed a strong correlation with %ΔSUVmax (P = 0.01) and percentage tumor to liver ratio change (P = 0.01). On comparison, these metabolic response tools showed a weak agreement (k, 0.28 with tumor to liver ratio, k, 0.38 with SUVmax). CONCLUSION: After neoadjuvant chemotherapy, 18F-fluorodeoxyglucose PET/CT can help to assess the response and guide the treatment. However, a larger study is warranted to evaluate their correlation with pathological response.

3.
J Biochem Mol Toxicol ; : e22781, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33797855

RESUMO

Nonavailability of glucose as a carbon source results in glyoxylate pathway activation, which metabolizes nonfermentable carbon for energy generation in Saccharomyces cerevisiae. Ucc1p of S. cerevisiae inhibits activation of the glyoxylate pathway by targeting Cit2p, a key glyoxylate enzyme for ubiquitin-mediated proteasomal degradation when glucose is available as a carbon source. Sro9p, a La-motif protein involved in RNA biogenesis, interacts physically with the messenger RNA of UCC1; however, its functional relevance is yet to be discovered. This study presents binary epistatic interaction between UCC1 and SRO9, with functional implication on the growth rate, response to genotoxic stress, resistance to apoptosis, and petite mutation. Cells with ucc1Δsro9Δ, as their genetic background, exhibit alteration in morphology, improvement in growth rate, resistance to apoptosis, and petite mutation. Moreover, the study indicates a cross-link between ubiquitin-proteasome system and RNA biogenesis and metabolism, with applications in industrial fermentation and screening for cancer therapeutics.

4.
Clin Nucl Med ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33826565

RESUMO

ABSTRACT: Prostate-specific membrane antigen (PSMA) is expressed on the endothelial cells of tumor-associated neovasculature of various nonprostatic benign and malignant neoplasms. Positive intense uptake on PET/CT imaging with 68Ga-labeled PSMA is noted in a patient with sinonasal glomangiopericytoma, and the same is noted to be absent following complete surgical excision. 68Ga-PSMA PET/CT may be a useful tool for early recurrence identification, differentiating recurrence from surgical site reparative tissues, and peptide receptor radionuclide therapy of residual lesions.

5.
Clin Nucl Med ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33826578

RESUMO

ABSTRACT: As prostate-specific membrane antigen (PSMA) expression is universal in juvenile nasopharyngeal angiofibroma, it is commonly used for specifically differentiating recurrences from surgical site reparative tissues. Postoperative contrast-enhanced MRI revealed a residual disease in the left pterygoid base, but there was no PET/CT uptake with 68Ga-labeled PSMA at the same site. In retrospect, in comparison with preoperative PET/CT, it was found that the pterygoid base pneumatization was showing enhancement in contrast-enhanced MRI and not in functional PSMA. Postoperative 68Ga-PSMA PET/CT is a useful clinical tool in ambivalent diagnostic conditions avoiding morbidities.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33836537

RESUMO

BACKGROUND: India's National Tuberculosis Elimination Programme (NTEP) provides free diagnosis and treatment services but does not monitor TB-related costs. This study aimed to estimate the direct and indirect costs borne by adult patients with newly diagnosed TB. METHODS: A longitudinal study in Ballabgarh block, Haryana (North India) was conducted. A total of 110 patients were interviewed and data regarding costs were collected at three points of time (after diagnosis, at the end of intensive phase and at the end of the treatment) using a semistructured questionnaire. The total direct (out-of-pocket expenses) and indirect (income lost) costs before and during treatment were calculated for patients who completed the treatment. RESULTS: We enrolled 110 patients with drug-sensitive TB; 6 patients could not complete the treatment. The TB-related median total cost was US$150 (IQR 65-335). The median prediagnosis and postdiagnosis costs were US$42 (IQR 19-313) and US$63 (IQR 10.2-190), respectively. The median direct and indirect costs were US$75 (IQR 36-148) and US$16 (IQR 0-197), respectively. A catastrophic cost was experienced by 18% (95% CI 12 to 27%) of households. CONCLUSION: Despite free diagnosis and treatment services, there is a substantial TB-related cost for TB care under the NTEP. Accelerated efforts are needed to achieve the target of zero catastrophic cost.

7.
Sci Rep ; 11(1): 7540, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824368

RESUMO

In plants, during growth and development, photoreceptors monitor fluctuations in their environment and adjust their metabolism as a strategy of surveillance. Phytochromes (Phys) play an essential role in plant growth and development, from germination to fruit development. FR-light (FR) insensitive mutant (fri) carries a recessive mutation in Phytochrome A and is characterized by the failure to de-etiolate in continuous FR. Here we used iTRAQ-based quantitative proteomics along with metabolomics to unravel the role of Phytochrome A in regulating central metabolism in tomato seedlings grown under FR. Our results indicate that Phytochrome A has a predominant role in FR-mediated establishment of the mature seedling proteome. Further, we observed temporal regulation in the expression of several of the late response proteins associated with central metabolism. The proteomics investigations identified a decreased abundance of enzymes involved in photosynthesis and carbon fixation in the mutant. Profound accumulation of storage proteins in the mutant ascertained the possible conversion of sugars into storage material instead of being used or the retention of an earlier profile associated with the mature embryo. The enhanced accumulation of organic sugars in the seedlings indicates the absence of photomorphogenesis in the mutant.

8.
Plant Cell Environ ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33797764

RESUMO

Yellow Stripe-Like (YSL) proteins are a family of plant transporters that are typically involved in transition metal homeostasis. Three of the four YSL clades (I, II and IV) transport metals complexed with the non-proteinogenic amino acid nicotianamine or its derivatives. No such capability has been shown for any member of clade III, but the link between these YSLs and metal homeostasis could be masked by functional redundancy. We studied the role of the clade III YSL protein MtSYL7 in Medicago truncatula nodules. MtYSL7, which encodes a plasma membrane-bound protein, is mainly expressed in the pericycle and cortex cells of the root nodules. Yeast complementation assays revealed that MtSYL7 can transport short peptides. M. truncatula transposon insertion mutants with decreased expression of MtYSL7 had lower nitrogen fixation rates and showed reduced plant growth whether grown in symbiosis with rhizobia or not. YSL7 mutants accumulated more copper and iron in the nodules, which is likely to result from the increased expression of iron uptake and delivery genes in roots. Taken together, these data suggest that MtYSL7 plays an important role in the transition metal homeostasis of nodules and symbiotic nitrogen fixation.

9.
Trop Doct ; : 494755211005205, 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33813980

RESUMO

Mauriac syndrome is rare; we share our experience of nine patients who presented at a young age with malnutrition, short stature, abdominal distention and deranged liver function.

10.
J Ethnopharmacol ; : 114115, 2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33852947

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Elaeagnus conferta Roxb. (Elaeagnaceae) is a subtropical shrub mainly native to India, Vietnam, Malaysia and South China, whose various parts are used for treatment of diabetes, gastric ulcers, pain, oxidative stress and pulmonary disorders. Though the other parts of the plant have been reported for their ethnic use i.e. fruits as astringent locally and for cancer systemically, leaves for body pain and flowers for pain in chest and the seeds are mentioned as edible, there is no report per se on the medicinal use of seeds. Based on the fact that seeds of closely resembling species i.e. Elaeagnus rhamnoides has demonstrated significant anti-gastroulcerative property, the probability of the seeds of E. conferta possessing similar activity seemed quite significant. AIM OF THE STUDY: Phytochemical investigation and assessment of pharmacological mechanism(s) involved in anti-ulcer effect of methanolic extract of the seeds of E. conferta. MATERIALS AND METHODS: Bioactive phytoconstituents were isolated by column chromatography. These were identified by spectroscopic techniques including infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) and mass spectrometry. Methanolic extract (MEC) of the seeds was prepared by cold maceration and its anti-ulcerogenic potential was evaluated using indomethacin (50 mg/Kg) and water immersion stress models in male rats. The animals were pre-treated with different doses of MEC (400 and 800 mg/Kg) and the therapeutic effect was compared with standard drug i.e. ranitidine (RANT; 50 mg/Kg). The ameliorative effects of MEC were investigated on gastric juice pH, total acidity, free acidity and ulcer index. The assays of malionaldehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and pro-inflammatory cytokines i.e. interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were carried out to find out the possible mechanism(s) of protection. Further, histopathological changes were also studied. RESULTS: Chromatography studies and further confirmation by spectroscopic techniques revealed the presence of four different compounds in MEC i.e oleic acid (1), stearic acid (2), ascorbic acid (3) and quercetin (4). MEC exhibited anti-ulcerogenic effect in dose dependent manner which may be attributed to suppression of pro-inflammatory cytokines (IL-6, TNF-α) and MDA (112.7%), and up-regulation of protective factors such as CAT (90.48%), SOD (92.77%) and GSH (90.01%). Ulcer inhibition, reduction in total and free acidity and increase in gastric juice pH were observed in MEC treated rats as compared to disease control animals. Histopathological findings confirmed decreased cell infiltration, less epithelial cell damage and regeneration of gastric mucosa in dose dependent manner. CONCLUSIONS: The anti-ulcer effect of MEC may be attributed to its ability to scavenge free radicals and anti-inflammatory property via suppression of TNF-α and IL-6, thus offers a complete and holistic approach for management of peptic ulcer.

11.
J Biomech Eng ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33834233

RESUMO

Osteogenesis Imperfecta (OI), also known as 'brittle bone disease', is a genetic bone disorder. OI bones experience frequent fractures. It is observed physical activity is equally beneficial in reducing OI bone fractures in both children and adults as mechanical stimulation improves bone mass and strength. Loading-induced mechanical strain and interstitial fluid flow stimulates bone remodeling activities. Several studies have characterized strain environment in OI bones, whereas, a very few studies attempted to characterize the interstitial fluid flow. OI significantly affect bone microarchitecture. Thus, the present study anticipates that canalicular fluid flow reduces in OI bone in comparison to healthy bone in response to physiological loading due to altered poromechanical properties. Hence, this work attempts to understand the canalicular fluid distribution in the single osteon model of OI and healthy bones. A poromechanical model of osteon is developed to compute pore-pressure and interstitial fluid flow as a function of gait loading pattern reported for OI and healthy subjects. Fluid distribution patterns are compared at different time-points of stance phase of the gait cycle. It is observed that fluid flow significantly reduces in OI bone. Additionally, flow is more static than dynamic in OI osteon in comparison to healthy subjects. The present work attempts to identify the plausible explanation behind low mechano-transduction capability of OI bone. This work may further be extended in designing better biomechanical strategies to enhance fluid flow in order to improve osteogenic activities in OI bone.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33852112

RESUMO

A novel coronavirus disease (COVID-19) continues to challenge the whole world. The disease has claimed many fatalities as it has transcended from one country to another since it was first discovered in China in late 2019. To prevent further morbidity and mortality associated with COVID-19, most of the countries initiated a countrywide lockdown. While physical distancing and lockdowns helped in curbing the spread of this novel coronavirus, it led to massive economic losses for the nations. Positive impacts have been observed due to lockdown in terms of improved air quality of the nations. In the current research, ten tropical and subtropical countries have been analysed from multiple angles, including air pollution, assessment and valuation of health impacts and economic loss of countries during COVID-19 lockdown. Countries include Brazil, India, Iran, Kenya, Malaysia, Mexico, Pakistan, Peru, Sri Lanka, and Thailand. Validated Simplified Aerosol Retrieval Algorithm (SARA) binning model is used on data collated from moderate resolution imaging spectroradiometer (MODIS) for particulate matters with a diameter of less than 2.5 µm (PM2.5) for all the countries for the month of January to May 2019 and 2020. The concentration results of PM2.5 show that air pollution has drastically reduced in 2020 post lockdown for all countries. The highest average concentration obtained by converting aerosol optical depth (AOD) for 2020 is observed for Thailand as 121.9 µg/m3 and the lowest for Mexico as 36.27 µg/m3. As air pollution is found to decrease in the April and May months of 2020 for nearly all countries, they are compared with respective previous year values for the same duration to calculate the reduced health burden due to lockdown. The present study estimates that cumulative about 100.9 Billion US$ are saved due to reduced air pollution externalities, which are about 25% of the cumulative economic loss of 435.9 Billion US$.

13.
J Cancer Res Ther ; 17(1): 46-50, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33723131

RESUMO

Aim: In this study, we evaluated the association of rs6964823 of the Ikaros Family Zinc Finger 1 (IKZF1) gene with the risk of colorectal cancer (CRC) within the population of Jammu and Kashmir (J and K). Materials and Methods: The variant rs6964823 of the IKZF1 gene was genotyped using the TaqMan allele discrimination assay for 578 individuals (182 CRC cases and 396 healthy controls). The association of single-nucleotide polymorphisms with the disease was evaluated using logistic regression. Results: It was observed that the variant rs6964823 (IKZF1) showed a significant association with an adjusted allelic odds ratio (OR) of 1.74 (1.34-2.27) at 95% confidence interval (CI), P ≤ 0.05. The dominant model (AA + AG vs. GG) was also applied, where the adjusted OR was 3.096 (2.011-4.76) at 95% CI, P > 0.05. Conclusions: It was found that the variant rs6964823 of the IKZF1 gene is associated with a higher risk of CRC within the population of J and K.

14.
Nucl Med Commun ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33741856

RESUMO

OBJECTIVE: This study evaluated the utility of 18F-fluorodexoyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in staging, grading, and prognostication of Stage III and IV soft tissue sarcomas (STSs). METHODS: Forty patients (Median age = 32.5 years; 25 men) with histologically proven STSs, prospectively underwent 18F-FDG-PET/CTs at baseline. Three-dimensional region of interests were drawn encompassing the lesions to calculate standardized uptake values (SUVs) and metabolic tumor volumes (MTVs). After segmentation, Haralick statistical texture analysis was performed. Follow-up was available for 35 patients. Survival at 6 months was 71.4% and at 1 year was 57.1%. RESULTS: American Joint Committee on Cancer Stage III was seen in 23 and Stage IV in 17 patients. None of the baseline quantitative and semi-quantitative parameters could predict response or progression. Only reduction in SUVmax in interim PET/CT correlated with baseline SUVmax (Spearman's Rho = 0.533; P = 0.019). Textural parameters namely 'contrast' in CT (P = 0.039) and 'difference entropy' in PET/CT (P = 0.051) could differentiate intermediate from high-grade lesions, with corresponding area under curves being 0.736 (0.533-0.889) and 0.700 (0.518-0.882). M1 disease [Hazard ratio (HR): 3.184 (1.179-8.595); P = 0.022], absence of surgical treatment [HR 0.305 (0.106-0.873), P = 0.027 with surgery], lower MTV/total tumor volume (TTV) [HR: 0.975 (0.953-0.997; P = 0.028] and progressive disease in interim PET/CT [3.483 (0.898-13.515); P = 0.056] were predictors of lower survival in univariate analysis. Only M1 disease was found to be reaching significance in multivariate analysis [HR = 2.683 (0.949-7.580); P = 0.063]. Baseline PET/CT changed management in 12.5% of patients [compared to local-imaging and high-resolution CT chest]; with detection of extra-pulmonary metastases. Though, interim and end of treatment PET/CTs detected more metastatic lesions, management was not impacted. CONCLUSION: 18F-FDG-PET/CT allows for more accurate M-staging in late-stage STSs, which in turn influences the option of curative surgical resection and thus impacts patient prognosis. Lower baseline MTV/TTV and progression in interim PET/CT are also associated with lower survival. Textural analysis may have a role in noninvasive grading.

15.
Nucl Med Commun ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33741861

RESUMO

INTRODUCTION: The objective of the study was to use fuzzy logic-based moving average filters for reducing noise from Tc-99m-sestamibi parathyroid images and to compare its performance with classical moving average filters. METHODS: Sixty-eight Tc-99m-sestamibi parathyroid images (33 image zoom 1.0, 35 images zoom 2.0) were filtered using symmetric triangular fuzzy filters with the moving average (TMAV), asymmetric triangular fuzzy filters with the moving average (ATMAV) and classical moving average filter (MAV) with moving average within a square window of dimension N × N pixels(N =3,5,7,9,11). The relative filtering performance was compared both objectively (using Brisque score) and subjectively [by two nuclear medicine physicians on a 4-point scale (1 = nondiagnostic; 2 = diagnostic; 3 = good; and 4 = excellent image quality)]. The nonparametric two-sample Kolmogorov-Smirnov test was applied to find the statistically significant difference between the quality of input and their corresponding filtered images. RESULTS: The Brisque score assigned to MAV filtered zoom 2.0 images (MAV_3, median = -0.61) were significantly smaller than that of their input images (median = 53.84, at P = 1) and fuzzy filtered images (TMAV_3, median = 0.44, at P = 0.89 and ATMAV_3, median =8.26, at P = 0.97). The sum of average subjective image quality score for input, MAV_3, TMAV_3, TMAV_5, ATMAV_3, and ATMAV_5 were 148, 221, 221.5, 198,171,253 and 237.5, respectively. CONCLUSION: On the basis of subjective assessment, the performance of ATMAV_3 fuzzy filter was found to be better compared to the classical moving average filter in reducing noise from Tc-99m-sestambi parathyroid images.

16.
Anim Biotechnol ; : 1-12, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33781169

RESUMO

Heat shock proteins (HSPs) act as a chaperone activity ensuring the folding, unfolding, and refolding of denatured proteins, which help in a protective role during thermal stress in dairy cattle. This study aimed to detect genetic variations of the HSPB6 gene and to determine their association with heat tolerance traits in Karan Fries cattle. Five single nucleotide polymorphisms (SNPs) (SNP 1-5) were reported in the Karan Fries cattle, which included three transitions viz. SNP1-g.161G > A, SNP2-g.436G > A, and SNP4-g.2152A > G and two transversions viz. SNP3-g.1743C > G, SNP5-g.2417A > T. The association analysis revealed that the three SNPs loci i.e., SNP1-g.161G > A, SNP2-g.436G > A, and SNP3-g.1743C > G were significantly (p < 0.01) associated with the respiration rate (RR) and rectal temperature (RT) (°C) traits. Furthermore, in the case of heat tolerance coefficient (HTC) trait was found significantly associated (p < 0.01) with SNPs loci i.e., SNP1-g.161G > A, SNP2-g.436G > A, and SNP3-g.1743C > G. The Hap 4 (GACAT) was found to more adaptable than cattle of other haplotypes as reflected by lower values of RR, RT and HTC. This study provides the first association analyses between the SNPs and haplotypes of HSPB6 gene and heat tolerance traits in Karan Fries cattle, which could be used as effective SNP markers in genetic selection for heat tolerance in cattle breeding program.

17.
Clin Nucl Med ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33782285

RESUMO

OBJECTIVES: Because prostate-specific membrane antigen (PSMA) expression is universal in juvenile nasal angiofibroma (JNA), PSMA PET/CT is commonly used in the postoperative setting using the postoperative angiofibroma radionuclide imaging study protocol. Our study aims to illustrate physiological PSMA ligand uptake distribution characteristics in the salivary glands, specifically the tubarial glands with tumor, to aid in accurate PSMA PET/CT analysis. STUDY DESIGN: Forty-three consecutive patients who underwent a dedicated head and neck spot PSMA PET/CT for JNA were evaluated retrospectively. PSMA SUVmax values in the tumor, tubarial, parotid, submandibular, and sublingual salivary glands were determined visually and quantitatively. RESULTS: All the tumors and the salivary glands showed increased tracer uptake. The median SUVmax ± SD ratios of the tumor, right and left tubarial gland, right and left parotid gland, right and left submandibular gland, and right and left sublingual gland were 2.7 ± 0.8 (range, 0.5-7.5), 3.8 ± 1.9 (range, 0.9-8.1), 4.7 ± 2.1 (range, 0.8-7.4), 9.5 ± 4.8 (range, 3.2-21.9), 9.2 ± 4.7 (range, 2.9-18.9), 10.4 ± 5.7 (range, 3.5-25.4), 10.4 ± 5.5 (range, 3.7-26.4), 6 ± 4.1 (range, 1.3-20.6), and 6.5 ± 4.2 (range, 1.8-19.7), respectively. The uptake in the tubarial glands was comparable with that of the tumor but less compared with other major salivary glands. CONCLUSIONS: Ours is the first study demonstrating the quantitative uptake of tubarial salivary glands in detail. Because the tubarial glands uptake and the anatomical location are similar to that of the tumor, these physiological uptakes must be borne in mind to circumvent false-positive interpretations and care must be given during the planning of stereotactic radiotherapy for JNAs.

18.
Cells ; 10(2)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670680

RESUMO

To define the growing significance of cellular targets and/or effectors of cancer drugs, we examined the fitness dependency of cellular targets and effectors of cancer drug targets across human cancer cells from 19 cancer types. We observed that the deletion of 35 out of 47 cellular effectors and/or targets of oncology drugs did not result in the expected loss of cell fitness in appropriate cancer types for which drugs targeting or utilizing these molecules for their actions were approved. Additionally, our analysis recognized 43 cellular molecules as fitness genes in several cancer types in which these drugs were not approved, and thus, providing clues for repurposing certain approved oncology drugs in such cancer types. For example, we found a widespread upregulation and fitness dependency of several components of the mevalonate and purine biosynthesis pathways (currently targeted by bisphosphonates, statins, and pemetrexed in certain cancers) and an association between the overexpression of these molecules and reduction in the overall survival duration of patients with breast and other hard-to-treat cancers, for which such drugs are not approved. In brief, the present analysis raised cautions about off-target and undesirable effects of certain oncology drugs in a subset of cancers where the intended cellular effectors of drug might not be good fitness genes and that this study offers a potential rationale for repurposing certain approved oncology drugs for targeted therapeutics in additional cancer types.

19.
J Biomol Struct Dyn ; : 1-15, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33715592

RESUMO

Severe acute respiratory syndrome-coronavirus2 (SARS-CoV2), a new coronavirus has emerged in Wuhan city of China, December 2019 causing pneumonia named Coronavirus disease-19 (COVID-19), which has spread to the entire world. By January 2021, number of confirmed cumulative cases crossed ∼104 million worldwide. Till date, no effective treatment or drug is available for this virus. Availability of X-ray structures of SARS-CoV2 main protease (Mpro) provides the potential opportunity for structure-based drug designing. Here, we have made an attempt to do computational drug design by targeting main protease of SARS-CoV2. High-throughput virtual screening of million molecules and natural compounds databases were performed followed by docking. After that, the protein-ligand complexes were optimized and rescoring of binding energies were accomplished through molecular dynamics simulation and Molecular mechanics Poisson Boltzmann surface area approaches, respectively. In addition, conformational effect of various ligands on protein was also examined through essential dynamics simulation. Three compounds namely ZINC14732869, ZINC19774413, and ZINC19774479 were finally filtered that displayed better binding affinities than N3 (known) inhibitor and formed conformationally stable complexes. Hence, the current study features the potential novel inhibitors against main protease of SARS-CoV2 which might provide an effective therapeutic strategy against COVID-19.Communicated by Ramaswamy H. Sarma.

20.
J Biomol Struct Dyn ; : 1-13, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710949

RESUMO

Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are cytosolic receptors implicated in recognition of intracellular pathogen associated molecular patterns (PAMPs) and danger associated molecular patterns (DAMPs). Depending upon their effector binding domain (EBD) at the C-terminal, the NLRs are categorized into NLRA, NLRB, NLRC, NLRP and NLRX. NOD1 is a pivotal player in immune responses against bacterial and viral invasions and interacts with pathogens via C-terminal leucine rich repeat (LRR) domain. This study aims at characterizing NOD1 in an economically important teleost of the Indian subcontinent, spotted snakehead Channa punctata. The understanding of pathogen-receptor interaction in teleosts is still obscure. In light of this, combinatorial approach involving protein modeling, docking, MD simulation and binding free energy calculation were employed to identify key motifs involved in binding iE-DAP. In silico analysis revealed that NOD1 consists of 943 amino acids comprising of one caspase recruitment domain (CARD) at N-terminal, one central NACHT domain and nine leucine rich repeat (LRR) regions at C-terminal. Structural dynamics study showed that the C-terminal ß-sheet LRR4-7 region is involved in iE-DAP binding. NOD1 was ubiquitously and constitutively expressed in all tissues studied. Differential expression profile of NOD1 induced by Aeromonas hydrophila infection was also investigated. Lymphoid organs and phagocytes of infected spotted snakehead showed significant downregulation of NOD1 expression. The current study thus gives an insight into structural and functional dynamics of NOD1 which might have future prospect for structure-based drug designing in teleosts.Communicated by Ramaswamy H. Sarma.

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