Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics.

Cardiovascular diseases continue to challenge global health, demanding innovative therapeutic solutions. This review delves into the transformative role of mesenchymal stem cells (MSCs) in advancing cardiovascular therapeutics. Beginning with a historical perspective, we trace the development of stem cell research related to cardiovascular diseases, highlighting foundational therapeutic approaches and the evolution of cell-based treatments. Recognizing the inherent challenges of MSC-based cardiovascular therapeutics, which range from understanding the pro-reparative activity of MSCs to tailoring patient-specific treatments, we emphasize the need to refine the pro-regenerative capacity of these cells. Crucially, our focus then shifts to the strategies of the fourth generation of cell-based therapies: leveraging the secretomic prowess of MSCs, particularly the role of extracellular vesicles; integrating biocompatible scaffolds and artificial sheets to amplify MSCs' potential; adopting three-dimensional ex vivo propagation tailored to specific tissue niches; harnessing the promise of genetic modifications for targeted tissue repair; and institutionalizing good manufacturing practice protocols to ensure therapeutic safety and efficacy. We conclude with reflections on these advancements, envisaging a future landscape redefined by MSCs in cardiovascular regeneration. This review offers both a consolidation of our current understanding and a view toward imminent therapeutic horizons.

Molecular Basis of Cerebral Vasospasm: What Can We Learn from Transcriptome and Temporal Gene Expression Profiling in Intracranial Aneurysm?

Cerebral vasospasm (CV) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH), and lacks a comprehensive molecular understanding. Given the temporal trajectory of intracranial aneurysm (IA) formation, its rupture, and development of CV, altered gene expression might be a molecular substrate that runs through these clinical events, influencing both disease inception and progression. Utilizing RNA-Seq, we analyzed tissue samples from ruptured IAs with and without vasospasm to identify the dysregulated genes. In addition, temporal gene expression analysis was conducted. We identified seven dysregulated genes in patients with ruptured IA with vasospasm when compared with those without vasospasm. We found 192 common genes when the samples of each clinical subset of patients with IA, that is, unruptured aneurysm, ruptured aneurysm without vasospasm, and ruptured aneurysm with vasospasm, were compared with control samples. Among these common genes, TNFSF13B, PLAUR, OSM, and LAMB3 displayed temporal expression (progressive increase) with the pathological progression of disease that is formation of aneurysm, its rupture, and consequently the development of vasospasm. We validated the temporal gene expression pattern of OSM at both the transcript and protein levels and OSM emerges as a crucial gene implicated in the pathological progression of disease. In addition, RSAD2 and ATP1A2 appear to be pivotal genes for CV development. To the best of our knowledge, this is the first study to compare the transcriptome of aneurysmal tissue samples of aSAH patients with and without CV. The findings collectively provide new insights on the molecular basis of IA and CV and new leads for translational research.

Mapping ACE2 and TMPRSS2 co-expression in human brain tissue: implications for SARS-CoV-2 neurological manifestations.

The Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets respiratory cells, but emerging evidence shows neurological involvement, with the virus directly affecting neurons and glia. SARS-CoV-2 entry into a target cell requires co-expression of ACE2 (Angiotensin-converting enzyme-2) and TMPRSS2 (Trans membrane serine protease-2). Relevant literature on human neurological tissue is sparse and mostly focused on the olfactory areas. This prompted our study to map brain-wide expression of these entry proteins and assess age-related changes. The normal brain tissue samples were collected from cerebral cortex, hippocampus, basal ganglia, thalamus, hypothalamus, brain stem and cerebellum; and were divided into two groups - up to 40 years (n = 10) and above 40 years (n = 10). ACE2 and TMPRSS2 gene expression analysis was done using qRT-PCR and protein co-expression was seen by immunofluorescence. The ACE2 and TMPRSS2 gene expression was observed to be highest in hypothalamus and thalamus regions, respectively. Immunoreactivity for both ACE-2 and TMPRSS2 was observed in all examined brain regions, confirming the presence of these viral entry receptors. Co-localisation was maximum in hypothalamus. Our study did not find any trend related to different age groups. The expression of both these viral entry receptors suggests that normal human brain is susceptibility to SARS-CoV-2, perhaps which could be related to the cognitive and neurological impairment that occur in patients.

Survival analysis in association with GST gene polymorphism and Treatment outcomes of Gemcitabine and Cisplatin/Carboplatin-based chemotherapy among patients with Gallbladder Carcinoma.

PURPOSE: Majority of the gallbladder cancer (GBC) cases are diagnosed at an advanced stage where chemotherapy alone (or in combination with other treatment methods) is mainly opted as therapeutic approach. However, success or failure of this approach largely depends on the interindividual genetic differences. Careful consideration on the genetic association could assist in the evaluation of patient's treatment response and survival rate. Hence, the present study aims to investigate the survival of patients with GBC and their treatment response to gemcitabine and cisplatin/carboplatin-based chemotherapy in association with Glutathione S-transferase (GSTs) gene polymorphism. MATERIAL AND METHODS: A total of 216 histologically confirmed cases of gallbladder cancer were recruited. A total of 180 patients were treated with gemcitabine and cisplatin/carboplatin-based chemotherapy. GSTM1, GSTT1, and GSTP1 genotypes were determined by multiplex PCR and by PCR restriction fragment length polymorphism (PCR-RFLP), respectively. The influence of genetic polymorphism on overall survival was analyzed by Kaplan-Meier method, survival rate difference was analyzed by log-rank test, and hazard ratio for mortality outcomes was estimated using Cox regression method. RESULTS: GBC patients having genotype GSTP1 (AG + GG) showed poor 3-year survival rate of 0.8% compared to 10.9% of GSTP1 (AA) genotype (χ2 = 6.456, P = 0.011). The multivariate Cox regression results showed that the death risk was significantly higher in GSTP1 (AG + GG) genotype (HR = 3.858, P = 0.050). We found no association of GSTM1 and GSTT1 gene polymorphism with the survival; however, the combined genotypes of GSM1/GSTP1, GSTT1/GSTP1, and GSTM1/GSTT1/GSTP1 were associated with survival (P = 0.053, 0.006, and 0.058, respectively). Increased death hazard was noted by the genotype combinations of GSTM1+/GSTP1AG + GG (HR = 3.484, P = 0.024), GSTM1-/GSTP1AG + GG (HR = 2.721, P = 0.014), GSTT1+/GSTP1AG + GG (HR = 20.690, P = 0.001), and GSTT1-/GSTP1AA (HR = 26.111, P < 0.0001). Our findings indicate that chemotherapy treatment response of GSTP1 (AG + GG) has 1.62-fold increased risk for progression compared to GSTP1 (AA) genotype (p = 0.018); however, none of the genotypes showed association with overall survival and death risk after chemotherapeutic treatment. CONCLUSION: We found that the presence of GSTP1 (AG + GG) genotype showed survival disadvantage and poor treatment outcomes in response to gemcitabine and cisplatin/carboplatin-based chemotherapy. This could serve as biomarker, and future research in pharmacogenomics will definitely pave the way for the development of better treatment approach for GBC.

The Role of Serum Matrix Metalloproteinase-9 as a Predictor of Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is one of the major causes of a poor neurological outcome following aneurysmal subarachnoid hemorrhage (aSAH). Several biomarkers, including matrix metalloproteinase-9 (MMP-9), have been evaluated to predict the development of DCI for timely management. This prospective cohort study was done on 98 patients with aSAH presenting within 72 h of the ictus. Serum samples were collected preoperatively, 7 days after ictus, 10 days after ictus, or when the patient developed DCI, whichever was earlier. The primary objective was to correlate the serum MMP-9 levels with the development of DCI. The secondary objectives were to correlate the serum MMP-9 levels with sonographic vasospasm and the neurological outcome. There was no correlation between the serum MMP-9 levels and the development of DCI (p = 0.37). Similarly, there was no correlation between the serum MMP-9 levels and the sonographic vasospasm (0.05) nor with the modified Rankin Scale (mRS) at discharge (p = 0.27), mRS at 3 months (p = 0.22), and Glasgow Outcome Scale Extended (GOSE) at 3 months (p = 0.15). Serum MMP-9 levels do not predict the development of DCI following aSAH.

Performance evaluation of hybrid constructed wetlands for nitrogen removal and statistical approaches.

Nitrogen pollution in water bodies has become a pressing environmental and public health issue worldwide, demanding the implementation of effective nitrogen removal strategies. This research paper delves into the performance evaluation of hybrid constructed wetlands (HCWs) as a sustainable and innovative approach for nitrogen removal, employing a comprehensive year-long dataset gathered from a practical setup. The study collected data under diverse operating conditions to investigate the effectiveness of HCWs in removing nitrogen. Results revealed that HCWs achieved nitrogen removal efficiencies ranging from 28% to 65%, influenced by temperature and hydraulic retention time. Optimal removal occurred at an average temperature of 28°C and a 4-day hydraulic retention time. Notably, performance declined during colder periods, with temperatures below 15°C. The study also aims to predict nitrogen removal by three modeling techniques, that is, artificial neural networks (ANNs), support vector machines Pearson VII kernel function (SVM PUK), and multiple linear regression (MLR). Prediction has been done considering temperature (TEMP), hydraulic loading rate (HLR), initial concentration of chemical oxygen demand (COD) (CODin), initial concentration of total nitrogen (TNin ), initial concentration of total phosphorous (TPin ), and initial concentration of turbidity (TBin ) as input parameters, whereas reduction of total nitrogen (RED TN) is regarded as output parameter. The performance of the soft computing techniques has been compared in terms of coefficient of determination (R2 ), root mean square error (RMSE), and mean absolute error (MAE). The analysis revealed that the performance of the SVM (PUK) model (R2 : 0.572, RMSE: 0.0359, MAE: 0.0294) for the prediction of TN reduction is superior followed by MLR (R2 : 0.562, RMSE: 0.0365, MAE: 0.0294) and ANN (R2 : 0.597, RMSE: 0.0377, MAE: 0.0301). The present study concludes that the treated effluent by the HCWs, using water hyacinth and water lettuce, is of fair quality, thus having potential application for the treatment of rice mill wastewater in warmer climates. Further, machine learning approaches employed in estimating the total nitrogen reduction by HCWs technology have shown promising applicability and utilization in such studies. PRACTITIONER POINTS: Hybrid constructed wetlands (HCWs) are effective in removing nitrogen from wastewater. The performance of HCWs in nitrogen removal can vary due to physical, chemical, and biological processes. The performance of the HCWs highly depends on temperature and hydraulic retention time. Artificial neural networks (ANNs) and support vector machines (SVMs) provided better predictions of nitrogen removal with high accuracy and low root mean square error.

Parry Romberg Syndrome: A Case Report and an Insight Into Etiology.

Parry-Romberg syndrome (PRS) is a rare degenerative disorder of unknown cause that causes slow, progressive atrophy on one side of the face. The cause may be a malfunction of the sympathetic nervous system, with or without neurological symptoms. Atrophy usually begins in childhood and progresses gradually over several years. Stabilization can take up to 20 years. There is no definitive cure for this condition, but once the condition is stabilized, reconstructive surgery of the damaged skin and soft tissue can correct the deformity. The objective of this article is to present an insight into the etiology of PRS with a case report of a 15-year-old male patient, who was diagnosed with PRS due to trauma and developed progressive hemifacial atrophy without neurological manifestations. PRS is a progressive disease that severely affects one side of the face. Because of its devastating effects on the entire body, treatment requires a multidisciplinary approach. Further research is needed to clearly understand the etiology and provide patients with accurate treatment plans.

Hard and Soft Tissue Relapse After Different Genioplasty Procedures: A Scoping Review.

The chin is a crucial component of facial aesthetics, and 20% of craniofacial problems require repair of the chin size, shape, and position. Genioplasty is used to treat irregularities in all three planes of the chin. Specific hard and soft tissue relapses following various genioplasty techniques have not been adequately studied in the literature to date. The purpose of this scoping review was to investigate the stability of hard and soft tissue changes achieved by different genioplasty procedures, six months after the procedure. A literature search was performed on PubMed, Web of Science, Embase, Wiley Online, Scopus, Google Scholar, Science Direct, and Cochrane databases from January 1, 2011 to October 31, 2022. Prospective and retrospective cohorts, case-control studies, observational studies, and randomized control trials, with at least 10 patients, which were written in English and evaluated the stability of different genioplasty procedures, with a follow-up period of at least six months were included. The manual and electronic search yielded 523 articles, and after complete screening, seven articles were selected (five with advancement genioplasty and two with reduction genioplasty) that met the eligibility criteria for review. The patients undergoing reduction genioplasty had a mean age of 24.15 years, compared to 20.5 years for augmentation genioplasty. The average follow-up period was 18.64 months for augmentation genioplasty and 10.5 months for reduction genioplasty technique. The relapse was assessed at pogonion, and it was noted that the average surgical advancement at hard tissue pogonion was 7.04 mm with a relapse of 0.69 mm after six months post-treatment. The average vertical movement of the hard tissue pogonion was 1.8 mm with a relapse of 0.74 mm. The average reduction at hard tissue pogonion was 3.2 mm in the vertical direction with a relapse of 0.2 mm and 0.8 mm reduction in soft tissue pogonion with a relapse of 0.3 mm. The soft to hard tissue ratio mentioned in the different studies ranged from 0.89 to 0.97. Both reduction and augmentation genioplasty are stable and reliable for altering the chin position for aesthetic purposes. The recommended mode of fixation is rigid fixation.

Dysregulated Genes and Signaling Pathways in the Formation and Rupture of Intracranial Aneurysm.

Intracranial aneurysm (IA) has the potential to rupture. Despite scientific advances, we are still not in a position to screen patients for IA and identify those at risk of rupture. It is critical to comprehend the molecular basis of disease to facilitate the development of novel diagnostic strategies. We used transcriptomics to identify the dysregulated genes and understand their role in the disease biology. In particular, RNA-Seq was performed in tissue samples of controls, unruptured IA, and ruptured IA. Dysregulated genes (DGs) were identified and analyzed to understand the functional aspects of molecules. Subsequently, candidate genes were validated at both transcript and protein level. There were 314 DGs in patients with unruptured IA when compared to control samples. Out of these, SPARC and OSM were validated as candidate molecules in unruptured IA. PI3K-AKT signaling pathway was found to be an important pathway for the formation of IA. Similarly, 301 DGs were identified in the samples of ruptured IA when compared with unruptured IAs. CTSL was found to be a key candidate molecule which along with Hippo signaling pathway may be involved in the rupture of IA. We conclude that activation of PI3K-AKT signaling pathway by OSM along with up-regulation of SPARC is important for the formation of IA. Further, regulation of Hippo pathway through PI3K-AKT signaling results in the down-regulation of YAP1 gene. This along with up-regulation of CTSL leads to further weakening of aneurysm wall and its subsequent rupture.

The Role of Adjunctive Chemical Solutions in the Treatment of Odontogenic Keratocysts: A Scoping Review.

Odontogenic keratocysts (OKC) are aggressive cysts with a high recurrence potential. Treating them with surgical enucleation procedures alone is associated with high recurrence rates; therefore, additional or supportive treatment approaches, such as peripheral osteotomy, cryotherapy, and chemical solutions, are warranted. The objective of the present review was to evaluate the existing literature on the efficacy of chemical approaches, such as Carnoy's solution (CS), in preventing recurrence after the enucleation of OKC. An electronic search was conducted on PubMed, Scopus, and Google Scholar databases to find articles published from January 2010 to December 2022 by using the Medical Subject Headings (MeSH) terms "Odontogenic Keratocyst" "Carnoy's Solution," "Treatment," and "Enucleation." Articles published in the English language were selected for the study. The PICOS criteria (population: patients with non-syndromic OKC with histopathological diagnosis and a minimum follow-up of six months; intervention and comparison: enucleation followed by adjunctive chemical therapy and standard procedure; outcome: recurrence rates; study design: retrospective and prospective studies, randomized controlled trials, and case series involving at least 10 cases of OKC) were employed. Studies involving syndromic (nevoid basal cell carcinoma) cases were excluded from the search. Seventeen studies fulfilled the inclusion criteria and the majority of them were retrospective studies, with a few case series. OKC was found more frequently in the mandible, with a recurrence rate of 11%, when treated with CS following enucleation after four years of follow-up. Modified Carnoy's solution (MC) was used in two studies. The mean follow-up period was 44 months. Based on our findings, adjuvant therapy using a chemical approach following enucleation is a more effective and beneficial modality for the treatment of OKC.

Differential Expression of Non-Coding RNAs in Stem Cell Development and Therapeutics of Bone Disorders.

Stem cells' self-renewal and multi-lineage differentiation are regulated by a complex network consisting of signaling factors, chromatin regulators, transcription factors, and non-coding RNAs (ncRNAs). Diverse role of ncRNAs in stem cell development and maintenance of bone homeostasis have been discovered recently. The ncRNAs, such as long non-coding RNAs, micro RNAs, circular RNAs, small interfering RNA, Piwi-interacting RNAs, etc., are not translated into proteins but act as essential epigenetic regulators in stem cells' self-renewal and differentiation. Different signaling pathways are monitored efficiently by the differential expression of ncRNAs, which function as regulatory elements in determining the fate of stem cells. In addition, several species of ncRNAs could serve as potential molecular biomarkers in early diagnosis of bone diseases, including osteoporosis, osteoarthritis, and bone cancers, ultimately leading to the development of new therapeutic strategies. This review aims to explore the specific roles of ncRNAs and their effective molecular mechanisms in the growth and development of stem cells, and in the regulation of osteoblast and osteoclast activities. Furthermore, we focus on and explore the association of altered ncRNA expression with stem cells and bone turnover.

An analysis of emergency surgery on coronavirus disease positive patients and their outcomes during the coronavirus pandemic: A retrospective observational study.

Background: The primary objective of this study was to determine the outcome of emergency surgery in coronavirus disease 2019 (COVID-19) patients with regard to presently existing physical status, and highlight its subspecialty distribution. Methods: This retrospective observational study was done on all patients who underwent emergency surgery between March 2020 and Dec 2021 and were positive for COVID-19. Data collection included the age of the patients, gender, diagnosis, the type of surgery performed, and outcome. Physical status was assessed, as per Modified Medical Research Council Dyspnoea Scale (MMRC) and Metabolic Equivalent Scale (METS). Results: A total of 89 patients were analyzed from March 2020 to Dec 2021. There were 63 females and 26 males. The average age of the males was 53.8 ± 8.9 years and the average age of the females was 29.1 ± 4.6 years. The maximum number of surgeries done was lower segment cesarean section (57.3%). 55 out of 60 (91%) cases had a good grade on the MMRC scale (Grade 0 and 1). 3 patients had Grade 4 MMRC scale and all 3 were oncology cases. As per the METS scale, 56/60 (93.3%) patients had METS >10. Conclusion: This study has demonstrated that 55 out of 60 (91%) of cases had a good grade on the MMRC scale (Grade 0 and 1) 6 months to 1-year post-surgery. As per the METS scale, 56/60 (93.3%) patients had METS >10. Most of the cases were asymptomatic COVID-19-positive and presently have good physical status as determined by the study.

Self-supervised Learning: A Succinct Review.

Machine learning has made significant advances in the field of image processing. The foundation of this success is supervised learning, which necessitates annotated labels generated by humans and hence learns from labelled data, whereas unsupervised learning learns from unlabeled data. Self-supervised learning (SSL) is a type of un-supervised learning that helps in the performance of downstream computer vision tasks such as object detection, image comprehension, image segmentation, and so on. It can develop generic artificial intelligence systems at a low cost using unstructured and unlabeled data. The authors of this review article have presented detailed literature on self-supervised learning as well as its applications in different domains. The primary goal of this review article is to demonstrate how images learn from their visual features using self-supervised approaches. The authors have also discussed various terms used in self-supervised learning as well as different types of learning, such as contrastive learning, transfer learning, and so on. This review article describes in detail the pipeline of self-supervised learning, including its two main phases: pretext and downstream tasks. The authors have shed light on various challenges encountered while working on self-supervised learning at the end of the article.

Transfer learning for image classification using VGG19: Caltech-101 image data set.

Image classification is getting more attention in the area of computer vision. During the past few years, a lot of research has been done on image classification using classical machine learning and deep learning techniques. Presently, deep learning-based techniques have given stupendous results. The performance of a classification system depends on the quality of features extracted from an image. The better is the quality of extracted features, the more the accuracy will be. Although, numerous deep learning-based methods have shown enormous performance in image classification, still due to various challenges deep learning methods are not able to extract all the important information from the image. This results in a reduction in overall classification accuracy. The goal of the present research is to improve the image classification performance by combining the deep features extracted using popular deep convolutional neural network, VGG19, and various handcrafted feature extraction methods, i.e., SIFT, SURF, ORB, and Shi-Tomasi corner detector algorithm. Further, the extracted features from these methods are classified using various machine learning classification methods, i.e., Gaussian Naïve Bayes, Decision Tree, Random Forest, and eXtreme Gradient Boosting (XGBClassifier) classifier. The experiment is carried out on a benchmark dataset Caltech-101. The experimental results indicate that Random Forest using the combined features give 93.73% accuracy and outperforms other classifiers and methods proposed by other authors. The paper concludes that a single feature extractor whether shallow or deep is not enough to achieve satisfactory results. So, a combined approach using deep learning features and traditional handcrafted features is better for image classification.

COVID-19: Social distancing monitoring using faster-RCNN and YOLOv3 algorithms.

As of March 31, 2021, the Coronavirus COVID-19 was affecting 219 countries and territories worldwide, with approximately 129,574,017 confirmed cases and 2,830,220 death cases. Social isolation is the most reliable way to deal with this pandemic situation. Motivated by this notion, this paper proposes a deep learning-based technique for automating the task of monitoring social distancing using surveillance cameras. To separate humans from the background, the proposed system employs object detection models based on F-RCNN (Faster Region-based Convolutional Neural Networks) and YOLO (You Only Look Once) algorithms. In the COVID-19 environment, these models track the percentage of people who violate social distancing norms on a daily basis. The authors compared the performance of both models in experimental work using the MS COCO dataset. Many tests were carried out, and we discovered that YOLOv3 demonstrated efficient performance with balanced FPS (frames per second).

Targeting bacterial biofilms using vancomycin and multivalent cell-penetrating peptide labeled quantum dots.

Bacterial biofilms are highly resilient microbial musters that are difficult to eradicate, driving the development of novel therapeutic strategies. The current study aims to investigate the therapeutic efficacy of cell-penetrating peptide-based targeted delivery of vancomycin functionalized quantum dots in eradicating biofilm formation in gram-positive and gram-negative bacterial strains. The conjugate was characterized using fluorimetry, UV-visible spectroscopy, gel electrophoresis, and zeta potential. The conjugate was then tested for antimicrobial and antibiofilm activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, and it demonstrated excellent antimicrobial as well as antibiofilm activity against all the tested strains. The findings indicated that the conjugate was capable of overcoming bacterial resistance of bacteria in addition to the eradication of biofilms at effective concentrations.

Radiation Exposure to the Personnel Performing Myocardial Blood Flow Quantification Study Using 13N-ammonia Positron Emission Tomography/Computed Tomography.

Purpose: The present study aimed to evaluate radiation exposure to staff performing coronary flow reserve (CFR) measurement using 13N-ammonia. Materials and Methods: The radiation exposure rate during the administration of 13N-ammonia for the rest and stress part of the study was noted using an ionization chamber-based calibrated survey monitor. The radiation exposure to persons involved in dispensing radioactivity (D1), administering radioactivity (D2) and monitoring the patient during pharmacological stress (D3) were measured using an energy compensated Si-diode personal pocket dosimeter. Results: The average dose received by individuals with dosimeters D1, D2, and D3 was 1.28 ± 0.79 µSv, 1.56 ± 0.51 µSv, and 0.88 ± 0.97 µSv per injection, respectively, during the rest of study and 1.56 ± 0.96 µSv, 2.64 ± 1.22 µSv, and 2.2 ± 1.7 µSv per injection, respectively, during stress study. The average exposure rate during the administration of 13N-ammonia at 0.5 m and 1.5 m from the injection site was found to be 259 µSv/h and 53.4 µSv/h, respectively, during the rest study and 301 µSv/h and 67.25 µSv/h, respectively, during stress study. Conclusion: The exposure to the staff performing CFR study with 13N-ammonia was well within prescribed limits by the International Commission on Radiological Protection 103. The CFR measurement with 13N-ammonia positron emission tomography/computed tomography can be included in routine workups of cardiac patients without the fear of radiation exposure.

GSTs genetic polymorphism, gene-environment interaction and association with gallbladder cancer risk in North Indian population: A case-controlled study.

AIM: In the present case-controlled study, we explored the role of genetic polymorphism in three xenobiotic metabolizing genes, GSTM1, GSTT1 and GSTP1, and their association to gallbladder cancer (GBC) risk in a North Indian population. Its etiology is influenced by genetic, food habits, lifestyle, and environmental factors. GBC incidence is significantly higher in the Gangetic belt, India. Therefore, we explored the prognostic factors in the susceptibility of GBC through gene-gene and gene-environment interaction in this region. MATERIAL AND METHODS: Genetic polymorphism was analyzed in 108 GBC patients from Kamala Nehru Memorial Cancer Hospital, Prayagraj and 142 matched controls. GSTM1 and GSTT1 genotypes were analyzed by multiplex PCR method, while restriction fragment length polymorphism (RFLP) was performed to analyze GSTP1 genotypes. Logistic regression analysis calculating the odds ratio (OR) and 95% confidence interval (CI) was performed to analyze the GBC risk. RESULTS: GSTT1 (null) genotype was at a significantly higher risk and susceptible to GBC (OR = 2.044, CI = 1.225-3.411, P = 0.006), while GSTM1 and GSTP1 genotypes did not show any association to GBC risk. After sex stratification, females diagnosed with GBC had higher GSTT1 (null) genotype (OR = 2.754, CI = 1.428-5.310, P = 0.003) compared to males. GBC patients dwelling in rural areas show higher GSTT1 (null) genotype with two-fold GBC risk (OR = 2.031, CI = 1.200-3.439, P = 0.008). Further, GBC patients with histopathology of adenocarcinoma also showed higher GSTT1 (null) genotype (OR = 2.113, CI = 1.248-3.578, P = 0.005). Gene-gene interaction between GSTT1 (non-null)/GSTP1 (Ile/Val + Val/Val), enhance the GBC risk (OR = 1.840, CI = 1.135-2.982, P = 0.013). CONCLUSIONS: The present study suggests that GSTT1 (null) genotype has higher susceptibility and risk towards GBC in North Indian population. Female patients, patients with histopathology of adenocarcinoma and rural dwelling GBC patients have higher GSTT1 (null) genotypes and may be at risk of developing GBC. The genotype combination GSTT1 (non-null)/GSTP1 (Ile/Val + Val/Val) has increased GBC susceptibility and may be considered as 'at risk' genotypes for GBC in North Indians.

Survival analysis and prognostic factors of the carcinoma of gallbladder.

BACKGROUND: The present study aims to evaluate the survival status of patients with gallbladder cancer (GBC) and explore the prognostic factors for the improvement and preventions. METHODS: The study consists of 176 patients with clinically diagnosed gallbladder cancer; the study was conducted between 2019 and 2021 registered at Kamala Nehru Memorial Cancer Hospital, Prayagraj, India. The survival rates were analyzed by the Kaplan-Meier method; survival rate difference was analyzed by log-rank test, prognosis factors; and hazard ratio for mortality outcomes was estimated using Cox regression method. RESULTS: The overall median survival time of patients was 5 months with the 1-year, 2-year, and 3-year survival rates of 24.4%, 8.5%, and 4.5%, respectively. The 3-year survival for patients with jaundice was 2.9%, liver infiltration (4.2%), gallstones (0.8%), and with advanced tumor grade (1.4%). Elderly GBC patients had lower survival rates (3.8%), while the 3-year overall survival for patients residing in urban areas dropped to zero. No patients in the tumor stage (T3/T4) and with distance metastasis stage survived in 3 years, while only 1.1% of patients with advanced nodal stage survived. On receiving surgery and radiation therapy, the 3-year survival rate increased to 19.5% and 35%, respectively. The results of multivariate analysis showed that urban region (HR = 1.568, p = 0.040), gallstone or not (1.571, p = 0.049), N stage (HR = 1.468, p = 0.029), and M stage (HR = 2.289, p < 0.0001) were independent risk factors for prognosis, while surgery or not (HR = 0.573, p = 0.030) was the protective factor for the prognosis of GBC. CONCLUSION: The overall survival of GBC in the Gangetic belt is poor. The geographical region of patients, gallstones, and N and M stage was the risk factors for prognosis, while surgery or not was the protective factor for the prognosis of GBC.

Metabolic Pathways, Enzymes, and Metabolites: Opportunities in Cancer Therapy.

Metabolic reprogramming enables cancer cells to proliferate and produce tumor biomass under a nutrient-deficient microenvironment and the stress of metabolic waste. A cancer cell adeptly undergoes a variety of adaptations in metabolic pathways and differential expression of metabolic enzyme genes. Metabolic adaptation is mainly determined by the physiological demands of the cancer cell of origin and the host tissue. Numerous metabolic regulators that assist cancer cell proliferation include uncontrolled anabolism/catabolism of glucose metabolism, fatty acids, amino acids metabolism, nucleotide metabolism, tumor suppressor genes, microRNAs, and many regulatory enzymes and genes. Using this paradigm, we review the current understanding of metabolic reprogramming in tumors and discuss the new strategies of cancer metabolomics that can be tapped into for cancer therapeutics.