IN VITRO CYTOGENETIC EFFECTS OF AGRIZIM AND BAYLETON ON HUMAN LYMPHOCYTES IN THE PRESENCE AND ABSENCE OF METABOLIC ACTIVATION

Agrizim and bayleton,two commonly usedagricultural fungicides in India,wereinvestigated for their genotoxicpotentialities on cultured humanlymphocytes by studying chromosomalaberrations and sister chromatid exchangesin the presence and absence of

<i>N-myc</i>Downstream Regulated Gene 1 Increases Differentiation Factors Level in Human Prostate Cancer Cells without Affecting Cell Proliferation and Cell Cycle Profiles

N-myc downstream regulated gene 1 (NDRG1), also known as differentiation related gene 1, was previously identified as an up-regulated gene upon cellular differentiation. Even though its sequence along with its expressional pattern in cancer cell lines are evident, the functional aspects concerning cell proliferation, viability, differentiation and cell cycle regulation of NDRG1 remains vague. The aim of the present study was to elucidate the functional role of NDRG1 in human prostate cancer. Our results showed basal levels of NDRG1 expression in PC-3 (poorly differentiated, null p53), DU-145 (moderately differentiated, mutant p53) and LNCaP (well-differentiated, wiled type p53). Nevertheless, NDRG1 sequencing assay disclosed no mutations in the gene. Furthermore, human cDNA of NDRG1 from normal placenta was cloned into a eukaryotic expression vector and transfected into the three cancer cell lines. This resulted in over-expression of NDRG1, which in turn markedly up regulated two differentiation markers of the prostate tissue, p21 and cytokeratin 8/18. Unpredictably, cell cycle progression, cell proliferation and DNA synthesis were unaffected following NDRG1 expression. These results revealed that NDRG1 is functional in prostate cancer cells and able to induce expression of differentiation factors through p53 independent pathway. However, the pathway downstream NDRG1, involving p21 and c8/18, regulating cell cycle progression and DNA synthesis is unfunctional. Loss of sensitivity to p21 cell cycle control may be associated with prostatic cancer behavior. Further studies are required to clarify the intra cellular molecular pathways affecting NDRG1 function in human prostate cancer.

Equivocal Differential Effect of NDRG1 in Human Ovarian Cancer Cells

Inactivation of tumor suppressor genes is a key factor in cancer regulation. N-myc downstream regulated gene 1 (NDRG1) is a tumor suppressor gene well known to be involved in carcinogenesis of numerous cancer types. The present study was designed to investigate the role of NDRG1 in human ovarian cancer, using SKOV-3 and SW626 (moderately and well differentiated cancer cells, respectively). Our results revealed that over-expressed NDRG1 significantly up-regulated the differentiation marker p21, in the ovarian cancer cell lines. This regulation led to decrease in cell viability and DNA synthesis rates in SW626 cells (83% and 89.5%, respectively). However, no effect on viability or on DNA synthesis was observed in SKOV-3 NDRG1-transfected cells. These findings prove that NDRG1 is indubitably functional in human ovarian cancer cells, as it up-regulated p21 expression. Nevertheless, this regulation showed differential effect on cell viability and DNA formation thus promoting the perception that downstream regulation of p21 could be inefficient in some cancer cells, a concept that needs to be further explored in order to understand its disability to play as regulator of cell cycle progression.

What Is Dentists’ Role in Modulating Environmental and Epigenetic Determinant in Oral Health of Diabetic Patients?

Background and Purpose: With the unexpectedly rapid increase in the prevalence of types of diabetes worldwide, this chronic disease is no longer being viewed as a systemic health issue, but also treated as the start of the deadly disease. As the sixth complication of diabetes, periodontitis is a chronic inflammatory condition that leads directly and indirectly to a severer condition of diabetes via its underlying mechanisms. Interestingly, both diseases are not been fully identified in their bidirectional relationships by researchers. Thus, healthcare agencies must pay appropriate attention. This literature review paper aims to investigate and discuss dentists’ role in modulating environmental and epigenetic determinants in the oral health of diabetic patients based on the bidirectional relationship between these diseases, their prevalence and how treatment of one disease affects the other. Methods: The authors conducted electronic searches in PubMed, Google Scholar, One Search UofT, ScienceDirect, and the National Library of Medicine. The paper also included gray literature from government resources related to the topic. The paper will review the epidemiology, pathogenesis, and epigenetics of both diabetes and periodontal disease and their functions with each other. Results: The literature has consistently shown that diabetes and periodontal disease have responded to the formation and severity of each other. Patients with pre- and diabetes have potentially higher risks of causing periodontal disease and other complications if adequate diagnosis and treatment are not involved timely. The combination of risk factors, including individual, social, environmental, and genetic, play a crucial role in the development of diabetes and the severity of periodontitis. Conclusions: Based on the results, the collaboration between dentists and other healthcare practitioners is inevitable in the overall development of treatment for both diseases. With the proper and updated knowledge, dentists can benefit patients’ overall physical conditions through strategic intervention in diabetes patients.

Enteric neuropathy in diabetes:Implications for gastrointestinal function

Diabetes,commonly known for its metabolic effects,also critically affects the enteric nervous system(ENS),which is essential in regulating gastrointestinal(GI)motility,secretion,and absorption.The development of diabetes-induced enteric neuropathy can lead to various GI dysfunctions,such as gastroparesis and irregular bowel habits,primarily due to disruptions in the function of neuronal and glial cells within the ENS,as well as oxidative stress and inflammation.This editorial explores the pathophysiological mechanisms underlying the development of enteric neuropathy in diabetic patients.Additionally,it discusses the latest advances in diagnostic approaches,emphasizing the need for early detection and intervention to mitigate GI complications in diabetic individuals.The editorial also reviews current and emerging therapeutic strategies,focusing on pharmacological treatments,dietary management,and potential neuromodulatory interventions.Ultimately,this editorial highlights the necessity of a multidisciplinary approach in managing enteric neuropathy in diabetes,aiming to enhance patient quality of life and address a frequently overlooked complication of this widespread disease.

Insulin resistance as the molecular link between diabetes and Alzheimer's disease

Diabetes mellitus(DM)and Alzheimer's disease(AD)are two major health concerns that have seen a rising prevalence worldwide.Recent studies have indicated a possible link between DM and an increased risk of developing AD.Insulin,while primarily known for its role in regulating blood sugar,also plays a vital role in protecting brain functions.Insulin resistance(IR),especially prevalent in type 2 diabetes,is believed to play a significant role in AD's development.When insulin signalling becomes dysfunctional,it can negatively affect various brain functions,making individuals more susceptible to AD's defining features,such as the buildup of beta-amyloid plaques and tau protein tangles.Emerging research suggests that addressing insulin-related issues might help reduce or even reverse the brain changes linked to AD.This review aims to explore the relationship between DM and AD,with a focus on the role of IR.It also explores the molecular mechanisms by which IR might lead to brain changes and assesses current treatments that target IR.Understanding IR's role in the connection between DM and AD offers new possibilities for treatments and highlights the importance of continued research in this interdisciplinary field.

Advancing diabetes management: Exploring pancreatic beta-cell restoration’s potential and challenges

Diabetes mellitus,characterized by chronic hyperglycemia due to insulin deficiency or resistance,poses a significant global health burden.Central to its pathogenesis is the dysfunction or loss of pancreatic beta cells,which are res-ponsible for insulin production.Recent advances in beta-cell regeneration research offer promising strategies for diabetes treatment,aiming to restore endogenous insulin production and achieve glycemic control.This review explores the physiological basis of beta-cell function,recent scientific advan-cements,and the challenges in translating these findings into clinical applications.It highlights key developments in stem cell therapy,gene editing technologies,and the identification of novel regenerative molecules.Despite the potential,the field faces hurdles such as ensuring the safety and long-term efficacy of regen-erative therapies,ethical concerns around stem cell use,and the complexity of beta-cell differentiation and integration.The review highlights the importance of interdisciplinary collaboration,increased funding,the need for patient-centered approaches and the integration of new treatments into comprehensive care strategies to overcome these challenges.Through continued research and collab-oration,beta-cell regeneration holds the potential to revolutionize diabetes care,turning a chronic condition into a manageable or even curable disease.

The effect of minimal shoes on arch structure and intrinsic foot muscle strength

Background:This prospective study explored the effects of endurance running(ER) in minimal versus standard running shoes on the foot’s superficial layer intrinsic muscles and the function of the longitudinal arch.Our hypothesis was that running in minimal shoes would cause hypertrophy in these muscles and lead to higher,stronger,stiffer arches.Methods:The hypothesis was tested using a sample of 33 healthy runners randomized into two groups,a control group shod in traditional running footwear and an experimental group shod in minimal support footwear,whose feet were scanned in an MRI before and after a 12-week training regime.Running kinematics as well as arch stiffness and height were also assessed before and after the treatment period.Results:Analysis of anatomical cross-sectional areas and muscle volumes indicate that the flexor digitomm brevis muscle became larger in both groups by 11%and 21%,respectively,but only the minimally shod runners had significant areal and volumetric increases of the abductor digiti minimi of 18%and 22%,respectively,and significantly increased longitudinal arch stiffness(60%).Conclusion:These results suggest that endurance running in minimal support footwear with 4 mm offset or less makes greater use of the springlike function of the longitudinal arch,thus leading to greater demands on the intrinsic muscles that support the arch,thereby strengthening the foot.

Introduction:The past,present,and future of research on running barefoot and in minimal shoes

Barefoot running has been around for millions of years,and it is safe to presume that for most of that time,the practice occasioned little interest.Our ancestors ran barefoot because they had no shoes.When footwear was first invented during the last 40,000 years (no doubt at different times and in different places),shoes were by necessity minimal-essentially sandals and moccasins-designed to protect the sole of the foot but lacking any of the sophisticated features and materials present in modem running shoes such as elevated cushioned heels,arch supports,and toe springs.Most of these features were invented in the 1970s,and they quickly became more popular and sophisticated as running underwent a worldwide boom.Today,the vast majority of runners think it is normal to wear cushioned running shoes,and would never dream of running without them.

Detection of cardiac myosin binding protein-C (cMyBP-C) by a phospho-specific PKD antibody in contracting rat cardiomyocytes

Protein phosphorylation plays an important role in physiological processes, such as muscle contraction. Phospho-specific antibodies have become powerful tools to study these processes. Cardiac myosin binding protein-C (cMyBP-C) is one of the proteins that make up the contractile apparatus of cardiomyocytes. Phosphorylation of cMyBP-C is essential for normal cardiac function, since dephosphorylation of this protein leads to its degradation and has been associated with cardiomyopathy. One of the upstream kinases, which phosphorylate cMyBP-C, is protein kinase D (PKD). While studying the role of PKD in cMyBP-C phosphorylation, we tried to analyze phosphorylation of PKD with a phospho-specific PKD-Ser744/748 antibody. Contrary to the expected 115 kDa, a signal was found for a 150-kDa protein. By MALDI-TOF mass spectrometry, we identified this protein to be cMyBP-C. These data were confirmed by immunostaining using the p-PKD-Ser744/748 antibody, which displayed a striated pattern similar to the one observed for a regular cMyBP-C antibody. To our knowledge there are no antibodies commercially available for phosphorylated cMyBP-C. Thus, the p-PKD-Ser744/748 antibody can accelerate research into the role of cMyBP-C phosphorylation in cardiomyocytes.

Role of Tyrosine Kinase Receptors in Growth Factor Mediated Signal Transduction, with Specific Reference to MAPK/Rasand p13k-Akt Containing Pathways in Oncogenesis: A Qualitative Database Review

Receptor Tyrosine kinases (RTKs) play a crucial role in the signal transduction pathways at cellular levels. RTK plays a vital role in cellular communication and transmission of signals to the adjacent cells and regulates different functions of the cell, such as cellular growth, differentiation, metabolism and motility. RTK s triggers growth factor receptors such as epidermal growth factor, insulin growth factor-1 receptor, platelet derived growth factor receptor, and fibro blast growth factor receptor and vascular endothelial growth factor receptor, thereby initiating and regulating cell growth and proliferation. MAPK/RAS and PI3/AKT pathways are the major pathways of RTK’s function. Dysregulation of these RTK’s and pathways often leads to many diseases such as Noonan Syndrome, Logius Syndrome, CFC syndrome and different types of cancer. Point mutation and over expression of receptors and mutations in Ras leads to 30% of human cancers. Also over expression of different growth factor receptors by RTK too lead to several types of cancers as Glioblastoma, Thyroid cancer, Colon cancer and Non-small cell lung cancer. PTEN mutation in PI3/AKT pathway often leads to carcinoma relative to Thyroid, Skin, Large intestine, eye and Bone. Therefore, these RTK’s often used as targets for cancer therapies. The medical sector uses various types of small molecule tyrosine kinase inhibitors such as ATP competitive inhibitors, Allosteric inhibitors and covalent inhibitors which are known as Afatinib, Crizotinib, Eroltinib, Icotinib, Lepatinib and Lenvatinib in treatment and management of differential carcinomas.

A Retrospective Study of Directed Blood Donations in the Kasungu District of Malawi

Since the discovery of blood circulation and transfusion, there has been an insatiable demand for voluntary blood donations throughout the world. However, gathering blood donors has never been easy because eligible donors constitute only a fraction of the general population and are often reluctant to donate. This is especially challenging in underprivileged countries of sub-Saharan Africa such as Malawi whose nationally run blood transfusion service struggles to maintain hospital blood banks. As a result, hospitals turn to their local communities for directed donations. A retrospective analysis from January 2014 to June 2016 of directed blood donor data from two hospitals in the Kasungu District of Malawi was conducted. The analysis of 2134 donations was carried out with respect to sex, age, hemoglobin concentration, blood group, and presence of transfusion-transmissible infections. On average, donors were 30 years of age and predominately male. Blood group O+ constituted more than half of all directed blood donations. Ultimately, about one third of donations were unable to be utilized for transfusion.

Serum resistin and the risk for hepatocellular carcinoma in diabetic patients

Hepatocellular carcinoma(HCC),the predominant type of liver cancer,is a major contributor to cancer-related fatalities across the globe.Diabetes has been identified as a significant risk factor for HCC,with recent research indicating that the hormone resistin could be involved in the onset and advancement of HCC in diabetic individuals.Resistin is a hormone that is known to be involved in inflammation and insulin resistance.Patients with HCC have been observed to exhibit increased resistin levels,which could be correlated with more severe disease stages and unfavourable prognoses.Nevertheless,the exact processes through which resistin influences the development and progression of HCC in diabetic patients remain unclear.This article aims to examine the existing literature on the possible use of resistin levels as a biomarker for HCC development and monitoring.Furthermore,it reviews the possible pathways of HCC initiation due to elevated resistin and offers new perspectives on comprehending the fundamen-tal mechanisms of HCC in diabetic patients.Gaining a better understanding of these processes may yield valuable insights into HCC’s development and progression,as well as identify possible avenues for prevention and therapy.

COVID-19 and liver injury in individuals with obesity

Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations,including liver damage commonly detected by a hepatocellular pattern from liver function tests.Liver injury is associated with a worse prognosis overall.Conditions associated with the severity of the disease include obesity and cardiometabolic comorbidities,which are also associated with nonalcoholic fatty liver disease(NAFLD).The presence of NAFLD,similarly to obesity,is associated with an unfavourable impact on the coronavirus disease 2019 outcome.Individuals with these conditions could present with liver damage and elevated liver function tests due to direct viral cytotoxicity,systemic inflammation,ischemic or hypoxic liver damage or drug side effects.However,liver damage in the setting of NAFLD could also be attributed to a pre-existing chronic low-grade inflammation associated with surplus and dysfunctional adipose tissue in these individuals.Here we investigate the hypothesis that a pre-existing inflammatory status is exacerbated after severe acute respiratory syndrome coronavirus 2 infection,which embodies a second hit to the underestimated liver damage.

Therapy-refractory gastrointestinal motility disorder in a child with c-kit mutations

Constipation and fecal impaction are frequent and distressing complaints in pediatric gastroenterology. Especially in neurologically handicapped children, treatment of severe forms of slow-transit constipation (STC) can be difficult. In the majority of cases, STC is of unknown etiology. However, in recent years, there is growing evidence that interstitial cells of Cajal (ICCs), which serve as electrical pacemakers and generate spontaneous electrical slow waves in the gastrointestinal tract, might play an important role in the pathophysiology of STC. It remains unclear whether morphological ICC alterations seen in affected patients are based on congenital developmental anomalies, or whether they are a consequence of long-term constipation with secondary damage of the gastrointestinal nervous system. To the best of our knowledge, we present the first case of a patient with histological alterations in ICC morphology who displayed multiple alterations of c-kit at the level of mRNA. The protein encoded by c-kit is the receptor tyrosine kinase Kit (CD117), which is crucial for development and function of ICCs. Therefore, these findings provide a new explanation for congenital alterations of ICC development that result in gastrointestinal motility disorders.

Sickle Cell Gene Transmission: Do Public Servants in Tamale, Ghana Have the Right Knowledge and Attitude to Curb It?

Introduction: Sickle cell disease (SCD) is exerting enormous public health and economic burden on many countries. To reduce these effects, the World Health Organization is urging countries, especially those in Africa, to increase public awareness of this disease. This study accessed whether public servants in Tamale, Ghana possess adequate knowledge and positive attitude towards SCD. Method: A total of 320 public servants within the Tamale Metropolis were invited to complete a questionnaire in a cross-sectional study. Data were analyzed using GraphPad 5.01. Association between different variables was tested. Results: The media was the main source of information for a majority of the 94.2% of respondents who had ever heard of SCD. Knowledge of respondents on transmission and testing of SCD was above 70% but they recorded less than 40% in SCD’s incurability, prevalence, effect of SCD on life span and pregnancy. The mean knowledge score of respondents was (11.1 ± 5.11)/22 or 50.7%. Only about a quarter knew their sickling status or that of their spouses before marriage or first child. Although 78.0% of respondents would call off marriages if they became aware of genetic incompatibility, the overall mean attitude, (2.857 ± 1.97)/ 7.0% or 40.8% was poor. There was a positive and significant correlation between the knowledge of respondents and their attitude towards SCD (r = 0.494, p < 0.0001) hence respondents working in the health sector and those with tertiary level education had better attitudes towards SCD. Conclusion: Public servants in Ghana have moderate knowledge of SCD but their attitude towards the disease was poor. Public servants least considered genetic incompatibility before entering conjugal relationships. This poor attitude means the campaign for the reduction of sickle cell gene transmission must be intensified. Governments need to increase their investment on educational campaigns aimed at changing attitude of persons through provision of more knowledge about SCD.

Mycobacterium avium subspecies paratuberculosis infects and multiplies in enteric glial cells

AIM: To establish the role of enteric glial cells during infection with Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn's disease. METHODS: In order to establish the role of enteric glial cells during infection with M. avium subspecies paratuberculosis (MAP) in Crohn's disease, Map adhesion experiments on enteric glial cells were performed as well as expression analysis of Map sigma factors during infection. RESULTS: In this study, for the first time, we found a high affinity of MAP to enteric glial cells and we analyzed the expression of MAP sigma factors under different conditions of growth. CONCLUSION: The fact that Map showed a high affinity to the glial cells raises concerns about the complicated etiology of the Crohn's disease. Elucidation of the mechanisms whereby inflammation alters enteric neural control of gut functions may lead to novel treatments for Crohn's disease.

Heat dissipating upper body compression garment:Thermoregulatory,cardiovascular, and perceptual responses

Purpose:The aim of the present study was to determine the effects of an upper body compression garment(UBCG)on thermoregulatory responses during cycling in a controlled laboratory thermoneutral environment(~23℃).A secondary aim was to determine the cardiovascular and perceptual responses when wearing the garment.Methods:Sixteen untrained participants(age:21.3±5.7 years;peak oxygen consumption(V02 peak):50.88±8.00 mL/min/kg;mean±SD)performed 2 cycling trials in a thermoneutral environment(~23℃)wearing either UBCG or control(Con)garment.Testing consisted of a 5-min rest on a cycle ergometer,followed by 4 bouts of cycling for 14-min at ~50%VO2 peak,with 1-min rest between each bout.At the end of these bouts there was 10-min of passive recovery.During the entire protocol rectal temperature(Trec),skin temperature(Tskin),mean body temperature(Tbody),and heat storage(HS)were measured.Heart rate(HR),VO2,pH,hematocrit(Hct),plasma electrolytes,weight loss(Wloss),and perceptual responses were also measured.Results:There were no significant differences between garments for Tskin,HS,HR,VO2,pH,Hct,plasma electrolyte concentration,Wloss,and perceptual responses during the trial.Trec did not differ between garment conditions during rest,exercise,or recovery although a greater reduction in Trec wearing UBCG(p=0.01)was observed during recovery.Lower Tbody during recovery was found when wearing UBCG(36.82℃±0.30℃ vs.36.99℃±0.24℃).Conclusion:Wearing a UBCG did not benefit thermoregulatory,cardiovascular,and perceptual responses during exercise although it was found to lower Tbody during recovery,which suggests that it could be used as a recovery tool after exercise.

Strike type variation among Tarahumara Indians in minimal sandals versus conventional running shoes

Purpose:This study examined variation in foot strike types,lower extremity kinematics,and arch height and stiffness among Tarahumara Indians from the Sierra Tarahumara.Mexico.Methods:High speed video was used to study the kinematics of 23 individuals.13 who habitually wear traditional minimal running sandals(huaraches).and 10 who habitually wear modern,conventional running shoes with elevated,cushioned heels and arch support.Measurements of foot shape and arch stiffness were taken on these individuals plus an additional sample of 12 individuals.Results:Minimally shod Tarahumara exhibit much variation with 40%primarily using midfoot strikes,30%primarily using forefoot strikes,and30%primarily using rearfoot strikes.In contrast,75%of the conventionally shod Tarahumara primarily used rearfoot strikes,and 25%primarily used midfoot strikes.Individuals who used forefoot or midfoot strikes landed with significantly more plantarflexed ankles,flexed knees,and flexed hips than runners who used rearfoot strikes.Foot measurements indicate that conventionally shod Tarahumara also have significantly less stiff arches than those wearing minimal shoes.Conclusion:These data reinforce earlier studies that there is variation among foot strike patterns among minimally shod runners,but also support the hypothesis that foot stiffness and important aspects of running form,including foot strike,differ between runners who grow up using minimal versus modem,conventional footwear.

National trends in alcohol and substance use among adolescents from 2005 to 2021:a Korean serial cross‑sectional study of one million adolescents

Background Although previous studies have provided data on early pandemic periods of alcohol and substance use in adolescents,more adequate studies are needed to predict the trends of alcohol and substance use during recent periods,including the mid-pandemic period.This study investigated the changes in alcohol and substance use,except tobacco use,throughout the pre-,early-,and mid-pandemic periods in adolescents using a nationwide serial cross-sectional survey from South Korea.Methods Data on 1,109,776 Korean adolescents aged 13–18 years from 2005 to 2021 were obtained in a survey operated by the Korea Disease Control and Prevention Agency.We evaluated adolescents’alcohol and substance consumption prevalence and compared the slope of alcohol and substance prevalence before and during the COVID-19 pandemic to see the trend changes.We define the pre-COVID-19 period as consisting of four groups of consecutive years(2005–2008,2009–2012,2013–2015,and 2016–2019).The COVID-19 pandemic period is composed of 2020(early-pandemic era)and 2021(midpandemic era).Results More than a million adolescents successfully met the inclusion criteria.The weighted prevalence of current alcohol use was 26.8%[95%confidence interval(CI)26.4–27.1]from 2005 to 2008 and 10.5%(95%CI 10.1–11.0)in 2020 and 2021.The weighted prevalence of substance use was 1.1%(95%CI 1.1–1.2)from 2005 to 2008 and 0.7%(95%CI 0.6–0.7)between 2020 and 2021.From 2005 to 2021,the overall trend of use of both alcohol and drugs was found to decrease,but the decline has slowed since COVID-19 epidemic(current alcohol use:βdiff 0.167;95%CI 0.150–0.184;substance use:βdiff 0.152;95%CI 0.110–0.194).The changes in the slope of current alcohol and substance use showed a consistent slowdown with regard to sex,grade,residence area,and smoking status from 2005 to 2021.Conclusion The overall prevalence of alcohol consumption and substance use among over one million Korean adolescents from the early and mid-stage(2020–2021)of the COVID-19 pandemic showed a slower decline than expected given the increase during the prepandemic period(2005–2019).