GLUT and HK: Two primary and essential key players in tumor glycolysis.

Cancer cells reprogram their metabolism to become "glycolysis-dominant," which enables them to meet their energy and macromolecule needs and enhancing their rate of survival. This glycolytic-dominancy is known as the "Warburg effect", a significant factor in the growth and invasion of malignant tumors. Many studies confirmed that members of the GLUT family, specifically HK-II from the HK family play a pivotal role in the Warburg effect, and are closely associated with glucose transportation followed by glucose metabolism in cancer cells. Overexpression of GLUTs and HK-II correlates with aggressive tumor behaviour and tumor microenvironment making them attractive therapeutic targets. Several studies have proven that the regulation of GLUTs and HK-II expression improves the treatment outcome for various tumors. Therefore, small molecule inhibitors targeting GLUT and HK-II show promise in sensitizing cancer cells to treatment, either alone or in combination with existing therapies including chemotherapy, radiotherapy, immunotherapy, and photodynamic therapy. Despite existing therapies, viable methods to target the glycolysis of cancer cells are currently lacking to increase the effectiveness of cancer treatment. This review explores the current understanding of GLUT and HK-II in cancer metabolism, recent inhibitor developments, and strategies for future drug development, offering insights into improving cancer treatment efficacy.

Potential role of p53 deregulation in modulating immune responses in human malignancies: A paradigm to develop immunotherapy.

The crucial role played by the oncogenic expression of TP53, stemming from mutation or amyloid formation, in various human malignancies has been extensively studied over the past two decades. Interestingly, the potential role of TP53 as a crucial player in modulating immune responses has provided new insight into the field of cancer biology. The loss of p53's transcriptional functions and/or the acquisition of tumorigenic properties can efficiently modulate the recruitment and functions of myeloid and lymphoid cells, ultimately leading to the evasion of immune responses in human tumors. Consequently, the oncogenic nature of the tumor suppressor p53 can dynamically alter the function of immune cells, providing support for tumor progression and metastasis. This review comprehensively explores the dual role of p53 as both the guardian of the genome and an oncogenic driver, especially in the context of regulation of autophagy, apoptosis, the tumor microenvironment, immune cells, innate immunity, and adaptive immune responses. Additionally, the focus of this review centers on how p53 status in the immune response can be harnessed for the development of tailored therapeutic strategies and their potential application in immunotherapy against human malignancies.

Runt-related transcription factors in human carcinogenesis: a friend or foe?

PURPOSE: Cancer is one of the deadliest pathologies with more than 19 million new cases and 10 million cancer-related deaths across the globe. Despite development of advanced therapeutic interventions, cancer remains as a fatal pathology due to lack of early prognostic biomarkers, therapy resistance and requires identification of novel drug targets. METHODS: Runt-related transcription factors (Runx) family controls several cellular and physiological functions including osteogenesis. Recent literatures from PubMed was mined and the review was written in comprehensive manner RESULTS: Recent literature suggests that aberrant expression of Runx contributes to tumorigenesis of many organs. Conversely, cell- and tissue-specific tumor suppressor roles of Runx are also reported. In this review, we have provided the structural/functional properties of Runx isoforms and its regulation in context of human cancer. Moreover, in an urgent need to discover novel therapeutic interventions against cancer, we comprehensively discussed the reported oncogenic and tumor suppressive roles of Runx isoforms in several tumor types and discussed the discrepancies that may have risen on Runx as a driver of malignant transformation. CONCLUSION: Runx may be a novel therapeutic target against a battery of deadly human cancers.

Association of Genital Chlamydia trachomatis Infection with Female Infer-tility, Study in a Tertiary Care Hospital in Eastern India.

BACKGROUND: Chlamydia trachomatis is recognized as one of the most common sexually transmitted pathogen in the world. 50-80% of infected females are asymptomatic. These untreated women are at risk of developing chronic sequelae leading to tubal pathology causing infertility. Infertility is defined as 1 year of unprotected intercourse without pregnancy. It may be primary or secondary. Aim : To find out the association of genital Chlamydia trachomatis infection with female infertility. Materials and Methodology : This case control study has been carried out in collaboration with R. G. Kar Medical College and Institute of Post Graduate Medical Education & Research, India, between July 2012 and June 2013. 40 infertile and 40 pregnant women were enrolled by purposive sampling as per inclusion and exclusion criteria. ELISA test was performed to detect serum IgG and IgA antibody against recombinant analogs of MOMP and 3 different PCR assays were done targeting MOMP and rRNA DNA from DNA extracted from first void urine. Results : IgG seropositivity was significantly higher (15% vs 0%, P=.0255) in cases than controls, though there was no significant difference in the proportion of IgA seropositivity among 2 groups (12.5% vs 2.5%, P=0.2007). Out of 80 samples 2 samples showed the production of amplicons with R1 - R2 primers. Only 1 sample gave positive result with production of amplicons with all the 3 primers used (R1 - R2, CT0005 - CT06 and JM15 - JM16). Conclusion : Persistent C. trachomatis infection must be recognized as a risk factor of infertility in this region of India. The low PCR positivity in FVU sample helps to conclude the diagnostic utility of serological tests in screening of infertile women.

Evaluation of virulent multidrug resistant Klebsiella infection status in a tertiary care hospital in Eastern India.

Klebsiella especially Klebsiella pneumoniae is gaining renewed interest because of emergence of multidrug resistance among klebsiellae associated with infections.These are now being recognised as one of the major threats to effective management of patients in hospital, especially in developing country like India. Pathogenic mechanism of klebsiella Infections are associated with virulence factors such as capsule and mucoid phenotype, etc. The present study was designed to determine the virulence factors and antibiogram of klebsiellae, isolated from various clinical specimen in a tertiary care hospital of West Bengal, India. A total of 2370 clinical specimens which include blood, urine, wound swab, sputum were processed for isolation and identification of klebsiella to the species level. For each klebsiella isolate demonstration of capsule was done by capsule relief stain and detection of mucoid phenotype was done by string test. Antibiogram was studied by Kirby-Bauer disc diffusion method according to Clinical and Laboratory Standard Institute (CLSI) guidelines. The results showed that klebsiella species were isolated and identified from 139 clinical samples (5.9% prevalence rate) among which 4 (2.9%) were Klebsiella oxytoca and the remaining 135 Isolates (97.1%) were Klebsiella pneumoniae. Out of 139 klebsiella isolates, capsule was demonstrated in 118 (84.9%) and 116 (83.4%) were positive for string test. Antibiogram revealed that most of isolates of Klebsiella pneumoniae were multidrug resistant.

A study on blood culture positivity and C-reactive protein variability in neonatal septicaemia at neonatal intensive care unit of a tertiary care hospital.

Neonatal septicaemia is an important cause of neonatal morbidity and mortality. Blood culture is the gold standard for diagnosis of neonatal septicaemia. Several laboratory investigations are available to detect neonatal sepsis, one important is 'sepsis screen' which includes C-reactive protein (CRP), micro -ESR, total WBC count including immature to mature (VT) ratio and absolute neutrophil count. Blood culture was done among 210 samples from neonatal intensive care unit (NICU), RG Kar Medical College with suspected septicaemia along with CRP estimation. Among all the parameters, clinical correlation of CRP is significant; 65.2% of patients has blood culture positive. CRP positivity varied in different organisms. CRP is a non-specific acute phase reactant and rises significantly after 12 hours onwards. It can be used as an important parameter in infant at risk of septicaemia (significant > 6 mg/dl) and early institution of antimicrobials therapy. It has got prognostic value.

Association of interferon-gamma, interleukin-10, and tumor necrosis factor-alpha gene polymorphisms with occurrence and severity of Eales' disease.

PURPOSE: Eales' disease (ED) is an idiopathic retinal vasculitis characterized by capillary nonperfusion and neovascularization. Previous reports on ED demonstrated that T-cell-mediated immunoresponse and differential cytokine production in inflammatory and angiogenic stage seem to influence the extent and severity of this disease. Therefore, the purpose of this study is to investigate the influence of cytokine gene polymorphisms on occurrence and severity of ED. METHODS: One hundred twenty-one patients with ED were recruited from an Eastern Indian population and compared with 223 matched healthy control subjects. Genotyping of IFN-γ, IL-10, and TNF-α were performed by amplification refractory mutation system polymerase chain reaction (ARMS-PCR). RESULTS: A statistically significant association was found between the IL-10 -1082AA (P = 0.002), TNF-α -308AA (P = 0.0017) genotypes and the IL-10 ATA haplotype (P = 0.0123) and the occurrence of ED. In addition IL-10 -1082GG (P = 0.0005), TNF-α -308GG (P < 0.0001) genotype were found to be protective against disease occurrence. A synergistically low IL-10/high TNF-α genotype increased the risk of development (P < 0.0001) and the severity (P = 0.019) of ED. CONCLUSIONS: These data suggest that a low IL-10-expressing and high TNF-α-expressing genotype of the host can influence the occurrence and severity of outcome of ED.

A hospital-based study to evaluate the incidence pattern of group A streptococcal throat infections from different age group patients.

Streptococcus pyogenes(group A) is a major pathogen capable of causing a wide range of diseases in different age group of people. In this study 100 patients were selected who presented with the complaint of sore throat. All the patients were divided in four age groups. Streptococcus pyogenes colonies were confirmed on the basis of beta-haemolysis, bacitracin sensitivity test, and latex agglutination test for group A. Out of a total of 100 samples, 42 were confirmed as group A streptococcus. From this study, it has been observed that all age groups, with maximum occurrence in 5-15 years age group, were suffering from group A streptococcal pharyngitis. Therefore every case of sore throat especially affecting children should be investigated to detect the causative agent for initiation of proper therapy so that the more serious outcome like acute rheumatic fever (ARF) and acute glomerulonephritis (AGN) can be prevented.

Rapid identification of mycobacterium species with the aid of multiplex polymerase chain reaction (PCR) from clinical isolates.

Mycobacteria are aerobic, nonspore forming, non-motile,single-cell bacteria.Of more than 40 currently recognized species of mycobacteria, Mycobacterium tuberculosis, the causative agent of human TB is the commonest pathogen for pulmonary and extra pulmonary tuberculosis cases. The other members of the Mycobacterium tuberculosis complex (MTC) or the nontubercular mycobacterium (NTM) produces similar diseases which cannot be differentiated from tuberculosis by clinical symptoms and signs. But this differentiation is important as the chemotherapy varies widely according to the strain of mycobacterium. The burden of morbidity and mortality of tuberculosis is rapidly growing worldwide, particularly with the HIV/AIDS epidemic. The strain identification of Mycobacterium remains a cumbersome, labor intensive and expensive procedure, which requires 3 to 12 weeks of time. The conventional methods of strain identification lack proper standardization and precise diagnosis. The prime objective of this study is to overcome these problems.A multiplex PCR using 3 amplicons of 165,365, and 541 base pair target sequences was done with a total number of 165 clinical isolates of suspected Koch's patients. Strain identification was compared both by conventional methods and multiplex PCR. The results of the study show that this multiplex PCR is supposed to be less complicated, less time consuming, cost-effective and superior to the conventional methods. It is also applicable for culture negative samples where strain identification is not possible by conventional approach.

Development and application of a new efficient and sensitive multiplex polymerase chain reaction (PCR) in diagnosis of leprosy.

India contributes about 80% of the global leprosy case load including case of fresh infection and reinfection. Due to lack of gold standard, diagnosis is done mainly based on routine clinical signs and symptoms, smear and histopathological evidences. There is a lot of lacunae in early confirmatory diagnosis in terms of sensitivity and specificity, especially in paucibacillary tuberculoid type. Moreover, the classification of different classes of leprosy is very important for selection of proper therapeutic schedule. Hence this study was undertaken to develop a multiplex polymerase chain reaction for the diagnosis and strain differentiation of M leprae. A multiplex polymerase chain reaction was developed using the primers R1 and R2 (a) amplifying 372bp DNA target from a repetitive sequence of M leprae and this repetitive sequence (372bp) that was used as a target DNA for amplification was reported to be specific for M leprae was not present in 20 mycobacterium species other than M leprae and primers TTCA and TTCB (b) amplifying (201bp) DNA target of variable sizes from the regions flanking TTC repeats of M leprae genome. This multiplex polymerase chain reacton developed in our laboratory revealed that the number of repeats at each locus might be variable among M leprae but they are found mostly in multibacillary (as the bacterial load is higher in multibacillary) type.

Studies on siderophore production of different diarrhoeagenic Escherichia coli.

In the present study, siderophore production capacity of various diarrhoeagenic E coli strains was tested on quantitative basis. The collected strains were classified under enteropathogenic E coli, enterotoxigenic E coli and entero-invasive E coli groups by using appropriate techniques. A few reference . enterotoxigenic E coli strains were also included in this study. The confirmation of various properties of enteropathogenic E coli, enterotoxigenic E coli and entero-invasive E coli strains was carried out by standard procedures. Several non-pathogenic E coli strains were also included in the study to assess their siderophore producing capacity. The results presented in the study showed that, the phenolate type of siderophore, that is enterochelin was predominantly produced by majority of these E coli strains. Only 30% of enteropathogenic E coli and 33% of enterotoxigenic E coli strains failed to produce any detectable level of enterochelin. On the other hand, only 50% of enteropathogenic E coli strains and all the entro-invasive E coli (100%) showed the positive aerobactin that is hydroxamate type of siderophore production ability. None of the enterotoxigenic E coli and non-pathogenic strains produced aerobactin.