Cisplatin is used as chemotherapeutic drug for oral squamous cell carcinoma (OSCC). However, OSCC cells develop resistance following long-term cisplatin exposure. Resistance against cisplatin chemo-therapy is accredited to the process of epithelial-to-mesenchymal transition, which in-turn has been linked to tumorrecurrence. miRNA deregulation, a common event in cancer, plays contributory role in chemo-resistance. Exosomes acts as the natural cargo for miRNA and facilitates inter-cell communication in the tumor micro-environment. Hence, exosomal-mediated miRNA transference may play essential role in drug resistance and serve as a target for cancer-therapy. miR-155 upregulation in OSCC has been described, however, its relevance in the observed chemo-resistance is unclear and also, if exosomes have any role in miR-155 regulation remain elusive. In the present study, we document for the first time the critical role of exosomes in mediating increments in miR-155 expression in OSCC cells that have acquired cisplatin resistance (cis Res cells). Importantly, exosomal transfer from cis Res to the cisplatin sensitive (cis Sens) cells was found to confer significant miR-155 induction in the recipient cis Sens cells. Restoration of miR-155 expression in cis Sens cells following miR-155 mimics treatment led to epithelial to mesenchymal transition, enhancements in their migratory potential as well as acquisition of resistant phenotype. Notably, similar augmentations in the migratory and chemo-resistant traits were seen upon delivery of exosomes from cis Res to the recipient cis Sens cells. Overall, our findings establish the significance of exosomalmediated miR-155 shuttling in the cisplatin-chemoresistance, commonly observed in OSCC cells, thereby providing rationale for targeting miR-155 signalling for oral cancer therapy.
Exosomes facilitate cross-talk amongst tumor cells, and thus also possess the potential to influence tumor-microenvironment and chemo-resistance. miRNAs, the important constituent of exosomes, are often dysregulated in cancer. They have been shown to play an essential role in tumor progression, metastasis, invasion, and resistance developed against different therapies. Acquisition of cisplatin-chemoresistance remains a major hurdle in the effective treatment of oral squamous cell carcinoma (OSCC). In this study, we demonstrate the importance of exosome-mediated miR-30a transfer in conferring cisplatin sensitivity in the otherwise resistant OSCC cells. Notably, miR-30a was found to be significantly reduced in exosomes isolated from the serum of OSCC patients, especially those having disease-recurrence, post cisplatin treatment. In conjunction with the findings in clinical samples, decreased miR-30a expression was observed in vitro in the cisplatin-resistant cultured OSCC cells compared to the cisplatinsensitive cells. Besides, we identified Beclin1, an autophagy-related marker, as a target of miR-30a and found it to be overexpressed in cisplatin-resistant OSCC cells, thus indicating at its possible negative-regulation by miR30a. Exosomes from the cisplatinresistant cells that have been transfected with miR-30a mimics, when delivered to the naïve cisplatin-resistant cells, caused not only the significant enhancements in miR-30a expression but also a concomitant decrease in Beclin1 and Bcl2 expression (autophagic and anti-apoptotic marker). More importantly, this together resulted in the sensitization of cisplatin-resistant cells. Thus, our study highlighted the role of exosomal-mediated miR-30a transfer in regaining sensitivity of the cisplatin-resistant OSCC cells via Beclin1 and Bcl2 regulation and hence suggests at its potential therapeutic role.
Diabetes mellitus (DM) is a gradually rising metabolic disease which is currently affecting millions of people worldwide. Diabetes is associated with various complications like nephropathy, neuropathy, retinopathy, diabetic foot, cognitive impairment, and many more. Evidence suggests that cognitive dysfunction is a rising complication of diabetes which adversely affects the brain of patients suffering from diabetes. Age‐related memory impairment is a complication having its major effect on people suffering from diabetes and Alzheimer's. Patients suffering from diabetes are at two times higher risk of developing cognitive dysfunction as compared with normal individuals. Multiple factors which are involved in diabetes related complications are found to play a role in the development of neurodegeneration in Alzheimer's. The problem of insulin deficiency and insulin resistance is well reported in diabetes but there are many studies which suggest dysregulation of insulin levels as a reason behind the development of Alzheimer's. As the link between diabetes and Alzheimer disease (AD) is deepening, there is a need to understand the plausible tie‐ins between the two. Emerging role of major factors like insulin imbalance, advanced glycation end products and micro‐RNA's involved in diabetes and Alzheimer's have been discussed here. This review helps in understanding the plausible mechanism underlying the pathophysiology of amyloid beta (Aβ) plaque formation and tau hyperphosphorylation as well provides information about studies carried out in this area of research. The final thought is to enhance the scientific knowledge on this correlation and develop future therapeutics to treat the same.
BACKGROUND Anaemia is perceived to be a major public health problem especially among adolescent females .Findings from National Family Health Survey NFHS (2005-06) indicate that 56% of the adolescent girls in India are anaemic and, of these 17% suffer from moderate to severe anaemia. The prevalence of anaemia in female adolescent age group is still an understudied subject. The aims of this study were to evaluate the recently initiated WIFS program for government school girls with respect to implementation and impact on trends in prevalence of Anaemia among adolescent girls in a Bengaluru rural school. MATERIALS AND METHODS Cross-sectional, descriptive exploratory research study was used. The choice of the school was based on commitment to administration of weekly iron-folic acid supplements (WIFS) programme. All the girl students from class 6 th to 10th of Government High and Senior Secondary school (age group, 11-19 years) who were a part of WIFS were enrolled as study participants. Qualitative data on anaemia awareness and diet history, compliance, side effects were taken from these girls. General information on age, height, weight were collected and BMI calculated. Hb estimation was done by Haemocue method. Statistical Analysis-Analysis were prepared by IBM SPSS Statistics version 22. RESULTS Out of the 95girls in the school, there were 81 girls (85.26%) reported to consume one tablet of Iron folic acid (IFA) weekly in the past 1 year, with no major side effects. The girls had knowledge about symptoms of anaemia and iron-rich diet. Hb estimates indicated 79.01% non anaemic, prevalence of anaemia was 20.99%; none of the girls had severe anaemia, 1.2% had moderate anaemia and the remaining 19.8% belonged to mild anaemia category, indicating a significant decline. The mean BMI of the study sample was 17.53 kg/m 2 with 67.9% underweight and 6.2% overweight. CONCLUSION Overall, in this school, the WIFS program was found to be well implemented with good compliance. The study indicates a positive impact of WIFS programme with a decline in anaemia prevalence, compared to previous national estimates. WIFS seems to be an impactful strategy to prepare adolescents for the reproductive age group with adequate iron stores. However, the general nutritional status could be further improved to improve the BMI.
Background:The triple burden of malnutrition (TBM) presents a significant threat to the health of mothers and their future generations, particularly in low-and middle-income countries. Though having adequate macro-and micronutrients and maintaining a healthy weight are essential for all, pregnant women require special attention. However, their nutrition status and dietary requirements are not focused upon during their clinical visits. Methods: International Federation of Gynecology and Obstetrics (FIGO) nutrition checklist was administered to 714 women for the first time in selected private healthcare facilities in 3 states of India. A descriptive analysis of data was done to assess their nutrition status and dietary pattern. Logistic regression was done to evaluate any significant association of their dietary and supplementary intake with the hemoglobin (Hb) levels. The feedback on FIGO checklist administration from 50 healthcare providers (HCPs) was also collected using a survey questionnaire. Result: The analysis of FIGO checklist data has shown that a significant proportion (48%) of women are overweight or obese and 33% are with low Hb. The increased Hb levels were significantly associated with supplement intake. However, the associations observed between any other dietary intake and Hb levels were insignificant. Healthcare providers considered the checklist as an important tool to encourage nutrition-related dialogues with women and recommended its use during clinical visits. Conclusion:The FIGO checklist holds promising potential as a nutrition intervention to curb the increasing burden of malnutrition by keeping health, nutrition status, and weight management in check. However, the challenges associated with its administration should be addressed to have a greater impact.
BACKGROUND Postpartum haemorrhage (PPH) and pre-eclampsia and eclampsia (PE/E) are the leading causes of pregnancy and childbirth-related complications and deaths, particularly in developing countries. FOGSI-Manyata skill transfer training is being implemented in private healthcare facilities in India, enabling ‘task-shifting’ to staff nurses by improving their knowledge and skills towards achieving desired maternal and perinatal outcomes. METHODS In this qualitative study, 4 focus group discussions (FGDs) with staff nurses and 14 in-depth interviews (IDIs) with head consultants of study facilities and assessors from different states (both metro and non-metro regions) were undertaken. Their experiences and perceptions about Manyata training, including its impact on building their capacity towards efficient handling of maternal complications during childbirth, were explored and the data was analysed through thematic analysis. RESULTS The two main overarching themes included: barriers to prevention, early identification and handling of complications, and post-training competency gained for effective management of complications. Lack of skilled staff trained in obstetrics and gynaecology, gaps in basic knowledge and skills in emergency obstetric care (EmOC), limited training opportunities at the workplace, and high staff turnover were identified as the factors contributing to the perceived importance of the training program. The competencies gained by staff nurses through Manyata training included readiness for prevention and early detection of complications (PPH and PE/E), improved understanding of specific causes of PPH, preparedness for timely management of both PPH and PE/E, and coordinated teamwork. CONCLUSIONS All the respondents strongly valued the Manyata training for effective management of maternal complications, PPH, and PE/E. Such in-service training, which is also appropriately tailored to the local context, along with the strong motivation of head consultants and staff nurses to upgrade themselves through continuous efforts, is required to achieve sustainable goals to reduce maternal and perinatal mortality.
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