Pregnant women with coronavirus infection are at a higher risk for severe diseases. In the present study, we evaluated and compared clinical characteristics and outcomes in pregnancy of normal females and females with SARS-CoV-2 infection. Our study was a cross-sectional study. The pregnant females were examined, their blood samples were taken for Covid Panel (D-Dimer, Ferritin, IL-6, CRP, PCT (Procalcitonin)); and oral-nasal swabs were taken for SARS-CoV-2 infection. Both SARS-CoV-2 positive and negative (control) females were followed up every trimester for any complication related to pregnancy. We found that females suffering from SARS-CoV-2 infection had reduced gestation periods, and had higher percentage of caesarean and pre-term delivery than SARS-CoV-2 negative females. Based on our findings, it appears that there exist close associations between SARS-CoV-2 infection in pregnant females and increased risk of reduced gestation periods, and spontaneous caesarean and pre-term delivery. However, more studies are still needed to validate present findings.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis research was sponsored by Multi-Disciplinary Research Units (MRUs) and DST, a grant by ICMR-Department of Health Research [Grant No: 6004].### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The study was approved by ethical committee of the Institution, Banaras Hindu University (No.Dean/2021/EC/2762).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present work are contained in the manuscript
Background: Chronic Myeloid Leukemia is characterized by the presence of the Philadelphia Chromosome (Ph) which contains the BCR::ABL1 fusion gene that occurs due to a reciprocal translocation between chromosomes 9 and 22. This accounts for up to 15 % of all adult leukemias [1]. Most patients treated with first line tyrosine kinase inhibitor (TKI) imatinib achieve durable response but may undergo relapse at some stage [2]. The most important mechanism that may confer imatinib resistance is point mutation within BCR::ABL kinase domain. Other generation ABL tyrosine kinase inhibitors such as dasatinib, nilotinib, bosutinib and ponatinib help to overcome imatinib resistance [3]. Sensitivity of the patient to each of the above TKIs depends upon the individual candidate mutation present. Thus, it is important to perform mutation analysis for effective therapeutic management of CML patients once they show imatinib resistance. We used direct sequencing to identify the different types of mutations responsible for resistance of imatinib treatment from north India. Methods: In this study, the patient resistance for the imatinib were analyzed for BCR::ABL kinase domain mutation by direct sequencing and the detected mutations along with their percentage prevalence were reported. Results: 329 patients with CML-CP were analyzed for BCR::ABL kinase domain mutation. Total 66 (20.06 %) patients out of 329 had mutation in at least one of the domains of BCR::ABL conferring resistance to different generations of TKI. Mutations in BCR::ABL kinase domain was observed in different domain of BCR::ABL. ATP binding P-Loop (42.42 %), Direct binding site (36.36 %), C-Loop (10.60 %), A-Loop (6.06 %), SH2 contact (3.03 %), SH3 contact (1.51 %). Conclusion: Total 20.06 % patients (66/329) show mutation in at least one of the structural motifs of BCR-ABL kinase domain, which further confer the resistance to a particular generation of TKI.
Endometriosis, is a gynecological disease, where uterine (eutopic) endometrial glands and tissues are present outside the intra-uterine locations, ectopic regions (pelvic peritoneum, fallopian tubes or ovaries). About 5-10% reproductive and 20-50% infertile women have endometriosis. Several factors like hormonal, environmental, genetic and immune system are involved in the pathogenesis of endometriosis both directly or indirectly altering the estrogen level and thus affecting the reproductive health of women. Current study was done with an aim to identify novel and potential biomarker for endometriosis using mRNA seq analysis. From raw gene expression profiles differentially expressed genes (DEGs) were identified and further their functional analysis was conducted. A total of 552 (312 up and 240 downregulated) DEGs were identified in samples from endometriosis suffering women when compared with control subjects. Major DEGs forming hubnodes like C3, PSAP, APP, GNG12 were found to be involved in various functions such as, epithelia cell differentiation and development, proteolysis, gland development, muscle fiber development, response to hormone stimulus. The identified DEGs can be directly or indirectly involved in the pathway of pathogenesis of endometriosis and can act as a potential biomarker for ectopic endometrium. Current study will provide a preliminary insight into the mechanism of endometriosis disease; however, it will require further detailed studies for its complete path of action.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis study did not receive any funding### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:From the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database (http://www. ncbi.nlm.nih.gov/geo/), the raw gene expression profile datasets (ID: GSE7305) were obtained for this study.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present work are contained in the manuscript
Background and objective Down syndrome (DS) is characterized by the presence of an additional chromosome; it is a typical chromosomal disorder causing intellectual disability in individuals. The diagnostic process for DS often involves conventional karyotyping, which can be time-consuming. Trisomy 21 and other chromosomal abnormalities may now be quickly and accurately diagnosed using quantitative fluorescence polymerase chain reaction (QF-PCR). In light of this, this study aimed to investigate chromosomal abnormalities in DS using conventional karyotyping and QF-PCR among the population in eastern Uttar Pradesh, India. Methods Blood samples from 40 individuals with clinically diagnosed DS were collected. Conventional karyotyping involved standard cytogenetic techniques, while QF-PCR utilized DNA extraction and analysis with chromosome -specific short tandem repeat (STR) markers. Results Various distinct physical characteristics were observed in the DS individuals, such as mongoloid slant and low -set ears. Karyotyping and QF-PCR analyses revealed different chromosomal configurations associated with DS trisomy 21, with additional chromosomal abnormalities found in some individuals, including partial monosomy 18 and mosaic trisomy 21. However, in a few cases, neither karyotyping nor QF-PCR revealed any abnormalities. Conclusions The study demonstrated that QF-PCR is a reliable and rapid method for diagnosing DS, providing results within 24 hours. This approach allows for the simultaneous diagnosis of a large number of samples and reduces the time required to obtain results. In the diagnostic procedure for DS, we believe QF-PCR will prove to be a useful tool. Furthermore, therapeutic interventions based on their clinical traits and molecular karyotyping can enhance the quality of life of people with DS.
Introduction Neonatal sepsis is a dynamic process where the rigorous evaluation of clinical signs along with appropriately selected biomarkers guides the diagnosis of sepsis. Procalcitonin (PCT) and C-reactive protein (CRP) are the two most commonly used diagnostic biomarkers used in sepsis. Sepsis remains the most important cause of mortality and morbidity in surgical neonates. A cross-sectional study was conducted to assess the prognostic predictability of PCT and CRP in neonatal surgical sepsis. Methods All the neonates admitted to the neonatal surgical intensive care unit between January 2019 and December 2020 with features of sepsis were included in the study. Blood cultures, CRP, and PCT on Day one (PCT1) and Day three (PCT3) of suspicion of sepsis were evaluated. The receiver operating characteristics curve was studied to estimate the probability of two markers to predict the mortality in neonatal sepsis. Results Of 102 surgical neonates, 63 neonates had early-onset sepsis while 23 (22.5%) neonates died and 30 neonates reported positive blood culture. There was a decline in the overall PCT trend from PCT1 and PCT3, while a significant PCT rise was noted for the non-survival group (p= 0.003). At cut-off of 5 mg/dl for CRP and 2.5 ng/dl for PCT1 and PCT3, the sensitivity (36.0%, 25.8%, 100%), specificity (84.1%, 83.3%, 97.5%), positive predictive value (52.2%, 73.9%, 91.3%), and negative predictive values (73.4%, 38.0%, 100%) were observed. Conclusion PCT on Day three of suspected sepsis has higher sensitivity, specificity, and accuracy for prognostication of surgical neonatal sepsis at the cut-off value of 2.5 ng/ml. The rising trend of PCT levels is indicative of a poor prognosis.
[This corrects the article DOI: 10.7759/cureus.29544.].
Rhino-orbital mucormycosis is a rare life threatening invasive fungal infection that has recently shown a very high mortality rate in India during COVID-19 pandemic. We have designed the present study to find out associations between COVID-19 induced rhino-orbital mucormycosis and concentrations of inflammatory markers, i.e. D-dimer, Ferritin, IL-6, CRP and PCT, in blood serum of Indian population. There were four groups in the study, viz. control group with healthy subjects, treatment group-1 with patients suffering from SARS-COV-2 infection, treatment group-2 with patients suffering from both SARS-COV-2 infection and rhino-orbital mucormycosis, and treatment group-3 with patients suffering from rhino-orbital mucormycosis after SARS-COV-2 infection recovery. Inflammatory markers were quantified with standard protocols, and recorded data were subjected to statistical analyses. We found that patients suffering from SARS-COV-2 infection were more susceptible to rhino-orbital mucormycosis, as they had higher concentrations of inflammatory markers in their blood than the other subjects. Diabetes mellitus, hypertension, cardiovascular diseases and renal disorders were the associated comorbidities with the patients. We also found higher concentrations of inflammatory markers in males than the females, indicating towards their higher susceptibility in developing rhino-orbital mucormycosis than females. Present study therefore suggests that the frequent occurrence of rhino-orbital mucormycosis in India during second wave of COVID-19 was possibly due to indiscriminate use of corticosteroids by COVID-19 patients. Subjects with previous history of comorbidities like diabetes mellitus, hypertension, cardiovascular disorders and renal diseases are the most susceptible population groups for developing infection. Moreover, males are at higher risk of developing mucormycosis than the females.
Background: Neonatal sepsis term is an infection of newborns <28 days of age. It is a common cause of death in developing countries. The receptor-gamma receptor FCGR2A has been shown to be associated with neonatal sepsis. It is an activating receptor found in many cell types such as monocytes, neutrophils, macrophages, platelets, and others. The receptor has a polymorphism (single-nucleotide polymorphism rs1801274) in its gene (FCGR2A) that encodes either a histidine (H) or arginine (R) at amino acid position 131. There are many studies showing the impact of these FCGR2A polymorphisms on sepsis. Our study aims to determine the prevalence of Fc-gamma receptor FCGR2A (rs1801274) polymorphism in neonatal sepsis and control in Eastern UP populations. Patients and Methods: We conducted a cross-sectional descriptive study of 590 patients (310 healthy individuals and 280 sepsis patients) to determine polymorphisms in the CD32A coding region in neonates. All individuals were genotyped for a variant at position 131 of the FcγRIIA gene. Discussion: In our study, the prevalence of FcγRIIa polymorphism is more in neonates with sepsis than in noninfected neonates. It was observed that the heterozygous allele (AG) were significantly increased in septic neonates when compared to the normal. Conclusion: Our data indicate that FcγRIIA genotyping can be used as a marker of genetic susceptibility to sepsis.
Background: 4-Nonylphenol (4-NP) is an Endocrine Disrupting Chemical (EDC), which interferes with endocrine (hormonal) system at certain doses.It is the primary final degradation product of Alkylphenolethoxylates (APE) which is a non-ionic surfactant, widely used in industries, agriculture and domestic purposes.4-NP is a persistent and ubiquitous Xenoestrogen with endocrine disrupting activities.It is highly prevalent in aquatic environments and is moderately bio-accumulative due to its lipophilic nature.Several studies have reported adverse effects of 4-NP on male reproductive system, including testicular abnormalities with gene expression profiling. Objective:The aim of our study was to investigate the multidimensional effects of 4-NP at varying doses (control, low and high) on BALB/C male mice testis having its exposure for about 21 days followed by gene expression studies. Materials and Methods: Male mice were given oral doses 21.25 mg/kg BW (Low Dose) and 85.0 mg/kg BW (High dose) of NP for 21 days. Result:The aromatase gene expression in low and high dose tissue samples varies (slightly higher) in respect to control testis samples. Conclusion:4-NP has an estrogenic effect on testes of male mice.
Introduction: The number and accumulation of hazardous chemicals are increasing gradually in the environment. These chemicals directly or indirectly affect the human health, and now-a-day’s these mostly include Endocrine-Disrupting Chemicals (EDCs). These EDC’s interfere with the normal hormonal signaling, leading to reproductive or physiological imbalance causing different diseases. Studies suggest that in these EDCs, 4-Nonylphenol (4-NP) is most commonly used after industrialisation and it is hazardous for all of us. But the complete or detailed studies regarding its effects on reproduction and physiology, mode of action, pathway followed and other related causative factors are yet to be studied. Aim: To examine the multigenerational effects of environmental EDC 4-NP on reproductive, histological and hormonal fitness of male mice exposed for 21 days. Materials and Methods: Male mice were given oral doses 21.25 and 85.0 mg/kg Body Weight (BW) of 4-NP for 21 days. After 21 days BW, organ weight, sperm viability tests were done to analyse the difference with respect to control group. Further histopathological [via Haematoxylin-Eosin (H&E), Periodic Acid Schiff (PAS) stain and Immunohistochemistry (IHC) techniques]and stress parameters (Superoxide Dismutase (SOD) and Lipid Peroxidation (LPO)) examinations were done in different organ tissue samples for detailed study. Results: The results showed that in male mice, 4-NP had a significant negative effect on the weight of its body organs. It further has an adverse effect on spermatogenesis and sperm quality with a resultant impact on male mice fertility with hormonal imbalance. Histopathological examination of the liver and testes biopsy samples illustrates that exposure to 4-NP at high doses induces occurrence of anomalies. 4-NP also causes decrease in SOD and increase in LPO, a parameter for increasing toxicity in the organs. Conclusion: Exposure to 4-NP induces reproductive and physiological toxic effects on male mice by causing hormonal imbalance.
Background: Endometriosis is a chronic inflammatory disease condition that affects an estimated 176 million women worldwide. The disease causes unbearable symptoms of pelvic pain and infertility that limit the quality of reproductive life of affected women. Objective: An attempt has been made to identify certain physiological and/or hormonal factors that may behave as reliable diagnostic markers to assess the various stages of endometriosis. Design: A retrospective population-based study. Material and Methods: Questionnaire-based study was conducted on females of Eastern Uttar Pradesh and Bihar that were suffering from endometriosis. Prevalent patients were characterized in terms of their socio-demographic and clinical characteristics, including validated infertility and chronic disease registries. Results: Progression of the disease was not affected by age and Body Mass Index (BMI) of subjects. The concentration of blood sugar (fasting and PP), and levels of Serum Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), T4, and Thyroid Stimulating Hormone (TSH) did not change as the disease progressed from stage 1 to 4. However, levels of serum estradiol, cortisol, prolactin, T3, and CA-125 increased as endometriosis progressed. There also existed close associations between CA-125, estradiol and cortisol, and stages of endometriosis. Conclusion: Elevated levels of CA-125, estradiol, and cortisol may behave as prominent diagnostic markers to assess the progression of the disease and to discriminate between various stages of endometriosis.
Accurate anthropometric measurements and critical analysis of growth data allow the clinician to promptly recognize children with short stature. Vitamin D deficiency (VDD) is widespread, yet it is the most underdiagnosed and undertreated nutritional deficiency in the world. The aim of this study was to determine the Effect of circulating 25-hydroxyvitamin D status in short stature patients undergoing Concurrent hormone therapy among children referred to the department of pediatric and endocrinology, Institute of medical Science, Banaras Hindu University. Methods: Blood was collected form the endocrinology OPD Sir Sunderlal Hospital IMS BHU complete blood count, calcium, phosphorus, alkaline phosphatase, 25 (OH) Vitamin D levels (by automated chemiluminescent immunoassay) on subjects suffering from Short Stature to record the details of their lifestyle, habits and familial history. All subjects were of Indian ethnicity from Eastern Uttar Pradesh and Bihar, the two states of northern Indian population. Patients were characterized in terms of their socio-demographic and clinically diagnosed characteristics, Evaluation included: detailed medical history, physical examination, laboratory tests, bone age and chromosomal analysis. Results: A total of 70 patients with short stature were involved in this study. The patient age for the study was taken 18 years (range 4 to 18 years) and 38 (54%) were male. The chosen patient to study their height and weight were below the 2 Standard deviation or third percentile there chronologic age in 57 (81%) patients. The leading cause of short stature in our population was Growth Hormone (GH) deficiency seen in 48 out of 70 (69%) patients. Conclusions: Several previous studies suggested that Vitamin D deficiency constitutes one of the major causes of short stature among fine-nurtured short stature children in India. If Primary recognition of short stature cannot help only average height attend but also improve their quality of life and social standing. All-purpose if diagnostic was done early need to be cognizant of and refer patients promptly to an endocrinologist for timely treatment.
Background: Endometriosis affects an estimated 176 million women worldwide, which constitutes 10% of the total female population causing debilitating symptoms of pelvic pain and infertility, which limits the quality of reproductive life of affected women. The present study aimed to assess the serum level of VEGF and pro-inflammatory marker IL-6 in cases and normal healthy control groups.Methods: VEGF and IL-6 serum levels were measured by competitive sandwich enzyme-linked immunosorbent assay (ELISA) from 34 subjects with surgically confirmed endometriosis, 16 subjects with adenomyosis and 18 similar age matched healthy controls with no clinical evidence of the disease or detectable endometriotic lesions at the time of surgical examination. Patients were characterized in terms of their socio-demographic and clinically diagnosed characteristics, including the validated infertility and chronic disease registries.Results: The mean serum level of VEGF was significantly (p<0.0001) higher in case of endometriosis (3887 ng/l) followed by adenomyosis (2588 ng/l) group and lower in case of normal healthy control (665 ng/l) group. The mean serum IL-6 was found to be highly significant (p<0.0001) in case of endometriosis (90.49 pg/ml) followed by adenomyosis (70.37 pg/ml) group and lower in case of normal healthy control (22.97 pg/ml) group.Conclusions: VEGF and IL-6 seems to play a crucial role in the implantation and development of endometriotic lesions, and the disease is associated with significant modulations in the serum levels of VEGF. IL-6 can be a reliable non-invasive diagnostic marker for endometriosis.
Introduction: Cervicobrachial Pain Syndrome (CBPS) is a disorder of enhanced mechanosensitivity to the neural structure, also known as lower cervical pain Syndrome. Cervicobrachial pain is managed by manual and traditional therapy, besides medical management. Aim: The aim of this scoping analysis was to determine the efficacy of the protocols for cervicobrachial syndrome treatment. Materials and Methods: Until March 2020, initial literature searches were performed through robust online electronic databases such as “Scopus” “MEDLINE via PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Sciences and Cochrane Controlled Trials Register in Cochrane Library, Physiotherapy Evidence Database (PEDro), ProQuest 5000 International, ProQuest Health and Medical Complete, and following keywords were used “Neck Disability Index, “Upper Limb Tension test, “Goniometry “Neck pain,” “Cervicobrachial Pain Syndrome,” Thirty six studies were included in this scoping study using PRISMA guidelines. Results: There is little evidence of manual and conventional physiotherapy treatment of cervicobrachial pain and its efficacy. Key advantages have been reported in manual therapy and exercises methods for pain relief and rehabilitation. Electrotherapeutic modalities, neck strengthening exercises, traction and methods for handling soft tissue are considered to be less effective in managing cervicobrachial pain syndrome relative to manual therapy. Lateral cervical glide and median nerve slider technique (neurodynamic) have useful effects as a treatment intervention in multiple cases of cervicobrachial pain syndrome, such as the median nerve slider technique and contra-lateral cervical glide technique. Recommendations for the management of cervicobrachial syndrome in practice should be encouraged in additional trials of innovative treatment methods. Conclusion: Studies should identify which cervicobrachial pain respond to specific interventions for immediate and effective response so as to increase the quality of life of the patients. Further research with innovative techniques of therapeutic approach would facilitate practice guidelines for the management of cervicobrachial syndrome.
Endometriosis disease affects about an estimated number of 176 million women worldwide, which constitutes ~10% of the total female population causing debilitating symptoms of pelvic pain and infertility, thus limiting the quality of reproductive life of an affected woman. Progestins now have became a mainstay of endometriosis suppression, out of which dienogest has been opted as a best option worldwide. Its an expertise literature review with recommendations on the use of dienogest in the context of various clinical considerations when treating endometriosis disease. Experts have reviewed and included those, which they found to be considered most relevant in clinical practices, based on their own clinical experiences. Long-term uses (>15 months) of dienogest for the management of endometriosis is presented, with experts concluding that the efficacy of dienogest must be assessed primarily for its impact on pain and quality of life of a woman. Fertility preservation, avoiding or delaying surgery, and managing the bleeding irregularities occurring because of this medical treatment are also considered here. Counseling women on potential bleeding risks before starting the treatment may be helpful, as the evidences suggest that few of them discontinues the treatment because of this reason outweighing the benefits. Overall, the evidences demonstrate that dienogest offers an effective and tolerable alternative in adjunct to surgery and provids many advantages over combined hormonal contraceptives for the treatment of endometriosis. But its important for all that treatment guidelines must be followed strictly with great care and must be tailored to the woman’s individual needs and their desires.
Severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) is the virus that causes COVID19 (coronavirus disease 2019), the respiratory illness responsible for the COVID-19 pandemic. It has created a devastating effect on humanity with social and economic depression. Europe and America were the hardest hit continents. India has also lost lives, making the country fourth most deadly worldwide. However, the infection and death rate per million and the case fatality ratio in Uttar Pradesh were substantially lower than in many States in India. Several factors have been proposed including genetics. One of the important facts is that a large chunk of Uttar Pradesh population is asymptomatic to the SARS-CoV-2 infection. Thus, the real infection in Uttar Pradesh is much higher than the reported number of cases. Therefore, the majority of people are already immune in the states. To understand the dynamics of real infection as well as the level of immunity against SARS-CoV-2, we have performed antibody testing (serosurveillance) in the urban region of ten districts in Uttar Pradesh in our survey, the prevalence frequency varied between 0.01-0.48, suggesting high variability of viral transmission between District. We also found out that the cases reported by the government were several folds lower than the real incidence of infection. This discrepancy is mainly driven by the higher number of asymptomatic cases. Overall, we suggest that with the high level of immunity developed against SARS-CoV-2 in the majority of the districts, the case fatality rate of second wave in India will be minor than first wave.
The Diabetes Mellitus (DM) is increasing in incidence and prevalence worldwide, taking the shape of the pandemic proportions, which is expected to increase further over a couple of decades.In 2019, an estimated 9.3% of the population (463 million people), globally had DM.Projection of future DM burden may increase to 10.2% (578 million people) by 2030 and 10.9% (700 million people) by next 25 years (2045).The decrease in immunity in diabetic patients has been a significant concern for physicians and patients alike.The role of mitochondria and it is cellular signaling can elaborate on this problem in depth.Mitochondria is a rich source of reactive oxygen species (ROS) and plays a crucial role in cellular metabolism for energy.They are targets of ROS and many different cellular signals like mitochondrial membrane apoptosis due to hyperglycemia and ROS.The interplay between oxidative stress and diabetes further activated, leading to increased permeability of mitochondrial membrane & apoptosis; this leads to a decrease in immunity in diabetic patients leading to increased mortality and morbidity.Hyperglycemia and ROS major pathways of apoptosis through mitochondrial activation in diabetic patients leading to decreased immunity.They can become drug targets for further intervention of this problem in Diabetic patients.
Endometriosis is an estrogen-dependent chronic inflammatory disease associated with substantial morbidity, including dyspareunia, dysmenorrhea, pelvic pain, multiple surgery, and infertility. This disease has a high impact on both woman’s physical and mental wellbeing. The etiology of endometriosis is complex and multifactorial. The risk factors associated with the development of endometriosis include family history, menstrual and reproductive cycle, low body mass index (BMI), diet, alcohol uses, smoking, environmental factors, immune system, genetic factors and intrinsic abnormalities in the endometrium. There exist many theories on the initiation and propagation of different types of endometriotic lesions and consequent biological disturbances, of which the most common is the Sampson’s theory according to which the retrograde flow of menstrual blood is linked to the development of endometriosis. Endometriosis affected women have a higher risk than the general female population, for ovarian cancer, coronary heart disease (CHD), and other long-term disease risks as well for autoimmune and atopic disorders. Therefore it becomes a necessity for the clinician not only to attain right diagnosis but also follow up for the other associated disorders. In this review, we have considered the crucial risk factors and biomarkers of the endometriosis as well as the possible pathogenesis towards the development of endometriosis and its prevention strategies. The currently available therapies for the control and treatment of endometriosis have also been elaborated.
Pyruvate kinase plays a pivotal role in regulating cell metabolism. The final and rate-limiting step of glycolysis is the conversion of Phosphoenolpyruvate (PEP) to Pyruvate, which is catalyzed by Pyruvate Kinase. There are four isomeric, tissue-specific forms of Pyruvate Kinase found in mammals: PKL, PKR, PKM1, and PKM2. PKM1 and PKM2 are formed bya single mRNA transcript of the PKM gene by alternative splicing. The oligomers of PKM2 exist in high activity tetramer and low activity dimer forms. The dimer PKM2 regulates the rate-limiting step of glycolysis that shifts the glucose metabolism from the normal respiratory chain to lactate production in tumor cells. Besides its role as a metabolic regulator, it also acts as protein kinase, which contributes to tumorigenesis. This review is focused on the metabolic role of pyruvate kinase M2 in normal cells vs. cancerous cells and its regulation at the transcriptional level. The review also highlights the role of PKM2 as a potential diagnostic marker and as a therapeutic target in cancer treatment.