Cancer insights from magnetic resonance spectroscopy of cells and excised tumors.

Multinuclear ex vivo magnetic resonance spectroscopy (MRS) of cancer cells, xenografts, human cancer tissue, and biofluids is a rapidly expanding field that is providing unique insights into cancer. Starting from the 1970s, the field has continued to evolve as a stand-alone technology or as a complement to in vivo MRS to characterize the metabolome of cancer cells, cancer-associated stromal cells, immune cells, tumors, biofluids and, more recently, changes in the metabolome of organs induced by cancers. Here, we review some of the insights into cancer obtained with ex vivo MRS and provide a perspective of future directions. Ex vivo MRS of cells and tumors provides opportunities to understand the role of metabolism in cancer immune surveillance and immunotherapy. With advances in computational capabilities, the integration of artificial intelligence to identify differences in multinuclear spectral patterns, especially in easily accessible biofluids, is providing exciting advances in detection and monitoring response to treatment. Metabolotheranostics to target cancers and to normalize metabolic changes in organs induced by cancers to prevent cancer-induced morbidity are other areas of future development.

Effect of low-level laser therapy plus exercise therapy on pain, range of motion, muscle strength, and function in knee osteoarthritis - a systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) is commonly associated with multiple musculoskeletal impairments. OBJECTIVE: The purpose of this review was (1) to investigate the effectiveness of LLLT plus ET on pain, ROM, muscle strength, and function in KOA immediately after therapy and (2) whether the effectiveness of LLLT plus ET could be sustained at follow-up (4 - 32 weeks). METHODS: Six databases were systematically searched upto December 2021 to find relevant articles. Included studies were RCTs written in English, which compared LLLT plus ET with placebo LLLT plus ET in KOA. Three independent reviewers extracted data and assessed the quality of included studies. Standard mean difference (SMD) was used in meta-analysis using random effect model. RESULT: Of the 6307 articles, 14 RCTs (820 patients) met the inclusion criteria. The results demonstrated that there was a significant difference in pain immediately after therapy (SMD: -0.58, p = 0.001) and at follow-up (SMD: -1.35, p = 0.05) in LLLT plus ET group. There were no significant differences in knee ROM, muscle strength, and knee function outcomes immediately and at follow-up. CONCLUSION: Our findings indicate that LLLT plus ET could be considered to alleviate pain in the KOA. LLLT reduces pain at 4-8J with a wavelength of 640-905nm per point applied for 10-16 sessions at a frequency of 2 sessions/week. An exercise therapy program at prescribed dosage involving major muscle groups might help. However, LLLT plus ET is no more effective than placebo LLLT plus ET in improving ROM, muscle strength, and function in KOA.

Blood flow restriction therapy with exercise are no better than exercise alone in improving athletic performance, muscle strength, and hypertrophy: a systematic review and meta-analysis.

BACKGROUND: The benefits of Blood Flow Restriction Therapy (BFRT) have gained attention in recent times. OBJECTIVE: This review aimed to evaluate the immediate (up to 24 hours), intermediate (up to 6 weeks), and long term (6-10 weeks) effects of BFRT plus exercises (EX) compared to EX only on athletic performance (sprint and jump performance), muscle strength, and hypertrophy in athletes and physically active population. METHODS: A literature search was conducted to select randomized controlled trials across four electronic databases from inception till April 2021. The search yielded twenty-seven studies in total. RESULTS: Based on eligibility criteria, twenty-one studies were analyzed. No differences were found between both groups for immediate (standardized mean difference [SMD] -0.02, 95% confidence interval [CI] -0.31, 0.27) and long-term effects (SMD -0.30, 95%CI -0.90, 0.30) on sprint performance. For jump performance, no significant effect was observed immediately (SMD -0.02 (95% CI -1.06, 1.02) and long term (SMD -0.40 (95% CI -1.46, 0.67). Similarly, muscle torque at intermediate (SMD 0.90 (95% CI -1.01, 2.81) and long term (SMD -0.54 (95% CI -1.19, 0.12), muscle strength at intermediate (SMD 1.12 (95% CI 0.20, 2.04) , and long term (SMD -0.07 (95% CI -0.56, 0.42) also showed non-significant effects. Muscle hypertrophy at intermediate (SMD 0.16 (95% CI -0.31, 0.63) and long term (SMD -0.20 (95% CI -0.90, 0.50) were not statistically significant. CONCLUSIONS: There was no significant difference observed in BFRT plus EX group compared to the EX-group on athletic performance, muscle strength, and muscle hypertrophy.

Dose-response and temporal ergogenic effects of ginseng supplementation in athletes and active participants: A systematic review and meta-analysis.

This review sought to assess the dose-response, i.e., low (<300 mg/day) and high (>300 mg/day), and temporal effects of ginseng, i.e., immediate, short-term (up to 4 weeks) and long-term (>4 weeks) in comparison to placebo on physical performance [visual analogue scale (VAS) level, vertical jump(VJ), rating of perceived exertion (RPE), peak power output (PPO)] and physiological measures [VO2 max, creatine kinase(CK), heart rate(HR)], in athletes and active participants. Search in four databases with English language constraints yielded 492 studies. Fourteen studies were shortlisted through PEDro scale by methodological quality evaluation. Ginseng exhibited significant short-term effect at high dosage for VJ improvement (SMD: -8.17, 95% CI: -16.28 to -0.06, p= 0.05). Ginseng had no effect on VAS (SMD: -0.65, 95% CI: -1.35 to 0.06, p= 0.07), RPE (SMD: -1.11, 95% CI: -2.57 to 0.35, p= 0.14), PPO (SMD: -0.70, 95% CI: -1.78 to 0.38, p= 0.20), HR (SMD: -0.54, 95% CI: -2.05 to 0.96, p= 0.48), CK (SMD: 0.33, 95% CI: -0.18 to 0.84, p= 0.21) and VO2 max (SMD: 0.08, 95% CI: -0.69 to 0.85, p= 0.08).The ginseng supplementation was found to have significant short-term effect at high dose only for VJ in athletic and active participants. Methodologically strong research is warranted to further consolidate these findings.

Outcome of Atypical & Complex Clubfoot Managed by Modified Ponseti Method-A Prospective Study.

Atypical or complex clubfoot constitutes a small number of cases. Due to the difference in complexity of anatomy, standard deformity correction by Ponseti is not effective. Hence a modified Ponseti method was advised which focuses on deformity differences for treatment. We conducted a prospective study to analyze the outcome in atypical or complex clubfoot treated with the modified Ponseti method. All the children of age less than 1 year were included in the study with atypical or complex clubfoot. Every case was treated according to the modified Ponseti method and tenotomy. Pirani scores were measured at pretreatment, each visit, before application of a brace, and at the latest follow-up. Statistical analysis of all continuous and categorical variables was done. A total of 30 patients (47 feet) were included in the study. Mean Pirani score improved from 5.69 at presentation to 0.45 at time of brace application and latest follow-up 0.34 (p < .001). Six patients (9 feet) had a relapse which was managed with recasting. The mean Pirani score of relapse was 0.72, which after correction reduced to 0.11 (p = .008). Six patients had cast-related complications which were managed with conservative treatment. With an increase in popularity of the Ponseti method, a greater number of complex clubfoot cases are seen due to inadequate reduction or slippage of cast or improper cast application techniques. All these need to be identified at an early age. This helps in proper treatment and improves the quality of life as well as foot appearance.

NMR Spectroscopy-based Metabolomics of Drosophila Model of Huntington's Disease Suggests Altered Cell Energetics.

Huntington's disease (HD) is a neurodegenerative disorder induced by aggregation of the pathological form of Huntingtin protein that has expanded polyglutamine (polyQ) repeats. In the Drosophila model, for instance, expression of transgenes with polyQ repeats induces HD-like pathologies, progressively correlating with the increasing lengths of these repeats. Previous studies on both animal models and clinical samples have revealed metabolite imbalances during HD progression. To further explore the physiological processes linked to metabolite imbalances during HD, we have investigated the 1D 1H NMR spectroscopy-based metabolomics profile of Drosophila HD model. Using multivariate analysis (PCA and PLS-DA) of metabolites obtained from methanolic extracts of fly heads displaying retinal deformations due to polyQ overexpression, we show that the metabolite imbalance during HD is likely to affect cell energetics. Six out of the 35 metabolites analyzed, namely, nicotinamide adenine dinucleotide (NAD), lactate, pyruvate, succinate, sarcosine, and acetoin, displayed segregation with progressive severity of HD. Specifically, HD progression was seen to be associated with reduction in NAD and increase in lactate-to-pyruvate ratio. Furthermore, comparative analysis of fly HD metabolome with those of mouse HD model and HD human patients revealed comparable metabolite imbalances, suggesting altered cellular energy homeostasis. These findings thus raise the possibility of therapeutic interventions for HD via modulation of cellular energetics.

1H nuclear magnetic resonance (NMR)-based serum metabolomics of human gallbladder inflammation.

OBJECTIVE AND DESIGN: We present in this article 1H nuclear magnetic resonance (NMR)-based metabolic approach to screen the serum metabolic alterations in human gallbladder inflammation with chronic cholecystitis (CC). MATERIAL/METHODS: Total of 71 human serum samples was divided into two groups, (n = 41, CC) and (n = 30 control). 1H NMR metabolic profiling was carried out for investigation of metabolic alterations. Multivariate statistical analysis was applied for pattern recognition and identification of metabolites playing crucial role in gallbladder inflammation. Receiver operating curve (ROC) and pathway analysis on NMR data were also carried out to validate the findings. RESULTS: Serum metabolites such as glutamine, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), alanine, branch chained amino acids (BCAA), histidine and tyrosine were found to be depleted whereas formate, lactate, 1,2-propanediol were found to be elevated in CC. Metabolic pathways associated with metabolite alteration have also been reported. CONCLUSIONS: NMR has been established for disease diagnosis along with identification of metabolic pattern recognition in biofluids. Gallstones cause inflammation of the gallbladder in the form of CC. Inflammation plays a major role in causation of gall bladder cancer and leads the way to malignancy. Metabolic analysis of CC may lead to early diagnosis of disease and its progression to gallbladder cancer.

Safety and effectiveness of response-guided therapy using pegylated interferon and ribavirin for chronic hepatitis C virus infection in patients on maintenance dialysis.

AIM: Treatment of hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD) is difficult. Addition of ribavirin to pegylated-interferon (Peg-IFN) may help to improve the treatment response. Further, treatment duration could be shortened using a response-guided treatment (RGT) approach. METHODS: We retrospectively reviewed records of treatment-naïve adult patients with ESRD and chronic HCV infection who had been treated with Peg-IFN and low-dose ribavirin using a RGT approach. Rapid responders (undetectable HCV-RNA at 4 weeks) received treatment for 12 weeks, and slow responders (HCV-RNA detectable at 4 weeks, but undetectable or with >2.0 log10 reduction at week 12) for 24 (genotype 3; GT3) or 48 (genotype 1; GT1) weeks. In those without such reduction (null responders), treatment was discontinued. RESULTS: Of 26 non-cirrhotic patients (GT1 15, GT3 11) treated, four (15%; GT1 3, GT3 1) were null responders. Twenty-two (85%) patients had either rapid (n = 14 (54%); GT1 10, GT3 4) or slow response (n = 8 (31%); GT1 2, GT3 6). Of them, 21 patients had undetectable RNA at the end of treatment; one could not complete the treatment and was lost thereafter. There were no deaths during treatment. Three patients relapsed and three others died in 6 months after stopping treatment. Overall, 15/26 (58%) patients attained SVR24. Fourteen patients underwent transplantation beginning one month after treatment completion, and all were relapse-free after 17 (14-24) months of follow-up. CONCLUSION: RGT using Peg-IFN and ribavirin was effective in ESRD patients on maintenance dialysis. Renal transplant was safely done within one month of completing such treatment.

P. vivax Malaria presenting as Thrombotic Microangiopathy.

INTRODUCTION: Acute kidney injury (AKI) is reported to occur in patients with falciparum malaria but not uncommon with vivax malaria. AKI, anemia, thrombocytopenia and jaundice is a recurrent finding in severe malaria and can mimic as thrombotic microangiopathy (TMA). Relationship of malaria with TMA is unclear till date however evidences suggest their association. METHODS & MATERIAL: We reviewed our electronic database to evaluate relationship of malaria with TMA, of cases of malaria, jaundice and AKI. RESULTS: 4 patients found to have P. vivax malaria and histopathologically confirmed TMA. All had fever, oliguria, jaundice at presentation. The time between onset of symptoms and admission ranged from 7 to 14 days. All had parasitemia at presentation so were treated with Artesuanate. Hemodialysis and Plasmapheresis was done in all patients. On follow-up all patients recovered and asymptomatic urinary abnormality persisting in one patient. CONCLUSION: High index of suspicion should be kept for TMA in a patient who has nonrecovering AKI with persistent anemia and thrombocytopenia even after clinical and laboratory evidences of recovery from malaria, as response to plasmapheresis seems excellent in this subset of malarial AKI. There could be a pathogenetic link between P.vivax and TMA though yet to be confirmed in larger studies.

NMR-Based Metabolic Snapshot from Minibronchoalveolar Lavage Fluid: An Approach To Unfold Human Respiratory Metabolomics.

The utility of mini bronchoalveolar lavage (mBAL) and its applicability in metabolomics has not been explored in the field of human respiratory disease. mBAL, "an archetype" of the local lung environment, ensures a potent technique to get the snapshot of the epithelial lining fluid afflicted to human lung disorders. Characterization of the mBAL fluid has potential to help in elucidating the composition of the alveoli and airways in the diseased state, yielding diagnostic information on clinical applicability. In this study, one of the first attempts has been made to comprehensively assign and detect metabolites in mBAL fluid, extracted from human lungs, by the composite use of 800 MHz 1D and 2D NMR, J-resolved homonuclear spectroscopy, COSY, TOCSY, and heteronuclear HSQC correlation methods. A foremost all-inclusive sketch of the 50 metabolites has been corroborated and assigned, which can be a resourceful archive to further lung-directed metabolomics, prognosis, and diagnosis. Thus, NMR-based mBALF studies, as proposed in this article, will leverage many more prospective respiratory researches for routine clinical application and prove to be a viable approach to mirror the key predisposing factors contributing to the onset of lung disease.

Prediction of susceptible biomarkers for end stage renal disease among North Indians.

AIM: Involvement of pro-inflammatory genes has been correlated with basic kidney diseases and end stage renal disease (ESRD). However, results at odds were often noted from such independent association studies. This study proposes a genome wide analysis approach to predict ESRD risk associated genes. METHODS: We included 42 single nucleotide polymorphisms (SNPs) showing association among north Indian ESRD cases and controls. ESRD cases comprised chronic glomerulonephritis (CGN), chronic interstitial nephritis (CIN), hypertension (HTN) and autosomal dominant polycystic kidney disease (ADPKD). Genotyping data obtained from our prior published reports were compared with Genome-Wide Association Studies (GWAS) SNPs retrieved from HapMap and GWASCentral databases using R-statistical package SNPAssoc. Linkage disequilibrium (LD), gene-gene interaction, classification and regression tree (CART) and pathway analysis were carried out in the present study supplemented with IL-6 and TNF-α levels estimation using enzyme linked immunosorbent assay (ELISA). RESULTS: Comparison of genotyping data with GWAS SNPs revealed significant associations for interleukin (IL)1-RN, IL-6, MTHFR, tumour necrosis factor-α (TNF-α) and CCR3 genes with ESRD. Nine SNPs were commonly associated with CGN, CIN, HTN, ADPKD and ESRD. LD (D = 0.9) and gene-gene interaction (P = 0.0002) analyses revealed significant associations for IL-6 and TNF-α genes. In a consistent manner, CART analysis and functional analysis servers predict predisposing effects for TNF-α and IL-6 with ESRD. Finally, higher body circulating levels were observed for mutant TNF-α and IL-6 alleles among ESRD. CONCLUSION: The study indicates significance for IL-6 and TNF-α gene with basic kidney diseases and ESRD. Extensive statistical tests, pathway analysis and functional assays also reflect attenuated level of significance for these SNPs. In future these may be brought from bench side to clinical practice as diagnostic biomarkers upon external and prospective replication and confirmation among other cohorts.

Hypoglycemic and Hypolipidemic Effects of Aloe vera Extract Preparations: A Review.

Obesity is considered to be an epidemic disease, and it is associated with several metabolic disorders. Pharmacological treatments currently available are not effective for prolonged treatment duration. So, people are looking toward new therapeutic approach such as herbal ingredients. Since ancient periods, different herbs have been used for remedy purposes such as anti-obesity, antidiabetes, and antiinflammatory. Among the several herbal ingredients, Aloe vera (Aloe barbadensis Miller) is widely used to curb the metabolic complications. Till date, reports are not available for the side effects of A. vera. Several researchers are used to different solvents such as aqueous solution, alcohol, ethanol, and chloroform for the A. vera extract preparations and studied their hypoglycemic and hypolipidemic effects in animal and human studies. Furthermore, little information was recorded with the active compounds extracted from the A. vera and their anti-obesity and antidiabetic effects in clinical studies. In this review, we made an attempt to compile all the available literature by using different search engines (PubMed, Scopus, and Google Scholar) on the A. vera extract preparations and the possible mechanism of action involved in carbohydrate and lipid metabolism.

Differential alteration in peripheral T-regulatory and T-effector cells with change in P-glycoprotein expression in Childhood Nephrotic Syndrome: A longitudinal study.

INTRODUCTION: Childhood Idiopathic Nephrotic Syndrome (INS) responds to glucocorticoid therapy, however, 60-80% of patients relapse and some of them become steroid non responsive. INS may occur because of T cell dysfunction, abnormal cytokines and podocytopathies which reverse on steroid treatment. The reason of relapses could be imbalances in T cells phenotypes and respective cytokines. Herein, we hypothesize that relapses in INS may occur due to imbalance in T-regulatory and T-effector cell with their respective cytokines and overexpression of P-gp on lymphocytes. METHODS: The frequency of peripheral blood CD4(+)CD25(+)FoxP3(+) Treg, CD4(+)IFN-γ(+) Th1 and CD4(+)IL-4(+) Th2 lymphocytes and their respective cytokines and P-gp expression on peripheral blood lymphocytes (PBLs) were analyzed in INS patients at baseline (n=26), during remission (n=24) and at relapse (n=15). RESULTS: Compared to baseline, the frequency of Tregs was significantly increased at remission and decreased during relapse. In contrast, the frequency of Th1 and Th2 lymphocytes was significantly decreased during remission and increased at the time of relapse. Similarly, expression of P-gp was significantly high at baseline and at the time of relapse as compared to remission. Levels of cytokines IL-10 and TGF-ß in the supernatant of stimulated PBMCs was increased during remission and decreased during relapse. In contrast, levels of IFN-γ and IL-4 were decreased during remission and increased at the time of relapse. CONCLUSIONS: Steroid therapy in INS induces decreased P-gp expression on PBLs along with increased frequency and cytokine response of T-regulatory cells, and reduced frequency and respective cytokine response of Th1 and Th2 cells during remission. However, reversal in the frequency and respective cytokines of T-regs, Th1 and Th2, and P-gp expression on PBLs occurs during relapses on follow-up.

Socioeconomic rehabilitation of successful renal transplant patients and impact of funding source: Indian scenario.

INTRODUCTION: Socio-economic rehabilitation is an important outcome parameter in successful renal transplant recipients, particularly in developing countries with low income patients who often depend on extraneous sources to fund their surgery costs. We studied the socioeconomic rehabilitation and changes in socioeconomic status (SES) of successful renal allograft recipients among Indian patients and its correlation with their source of funding for the surgery. MATERIALS AND METHOD: A cross-sectional, questionnaire-based study was conducted on 183 patients between January 2010 to January 2013. Patients with follow up of at least 1 year after successful renal transplant were included. During interview, two questionnaires were administered, one related to the SES including source of funding before transplantation and another one relating to the same at time of interview. Changes in SES were categorized as improvement, stable and deterioration if post-transplant SES score increased >5%, increased or decreased by <5% and decreased >5% of pre-transplant value, respectively. RESULTS: In this cohort, 97 (52.7%), 67 (36.4%) and 19 (10.3%) patients were non-funded (self-funded), one-time funded and continuous funded, respectively. Fifty-six (30.4%) recipients had improvement in SES, whereas 89 (48.4%) and 38 (20.7%) recipients had deterioration and stable SES. Improvement in SES was seen in 68% patients with continuous funding support whereas, in only 36% and 12% patients with non-funded and onetime funding support (P = 0.001) respectively. Significant correlation was found (R = 0.715) between baseline socioeconomic strata and changes in SES after transplant. 70% of the patients with upper and upper middle class status had improving SES. Patients with middle class, lower middle and lower class had deterioration of SES after transplant in 47.4%, 79.6% and 66.7% patients, respectively. CONCLUSIONS: Most of the recipients from middle and lower social strata, which included more than 65% of our patient's population, had deteriorating SES even after a successful transplant. One-time funding source for transplant had significant negative impact on SES and rehabilitation.

Burden and predictors of hypertension in India: results of SEEK (Screening and Early Evaluation of Kidney Disease) study.

BACKGROUND: Hypertension (HTN) is one of the major causes of cardiovascular morbidity and mortality. The objective of the study was to investigate the burden and predictors of HTN in India. METHODS: 6120 subjects participated in the Screening and Early Evaluation of Kidney disease (SEEK), a community-based screening program in 53 camps in 13 representative geographic locations in India. Of these, 5929 had recorded blood pressure (BP) measurements. Potential predictors of HTN were collected using a structured questionnaire for SEEK study. RESULTS: HTN was observed in 43.5% of our cohort. After adjusting for center variation (p < 0.0001), predictors of a higher prevalence of HTN were older age ≥ 40 years (p < 0.0001), BMI of ≥ 23 Kg/M2 (p < 0.0004), larger waist circumference (p < 0.0001), working in sedentary occupation (p < 0.0001), having diabetes mellitus (p < 0.0001), having proteinuria (p < 0.0016), and increased serum creatinine (p < 0.0001). High school/some college education (p = 0.0016), versus less than 9th grade education, was related with lower prevalence of HTN. Of note, proteinuria and CKD were observed in 19% and 23.5% of HTN subjects. About half (54%) of the hypertensive subjects were aware of their hypertension status. CONCLUSIONS: HTN was common in this cohort from India. Older age, BMI ≥ 23 Kg/M2, waist circumference, sedentary occupation, education less, diabetes mellitus, presence of proteinuria, and raised serum creatinine were significant predictors of hypertension. Our data suggest that HTN is a major public health problem in India with low awareness, and requires aggressive community-based screening and education to improve health.

Effect of Aloe vera (Aloe barbadensis Miller) on survivability, extent of proteolysis and ACE inhibition of potential probiotic cultures in fermented milk.

BACKGROUND: In the present investigation, the effect of Aloe vera gel powder on angiotensin-converting enzyme (ACE) inhibitory activity, extent of proteolysis during fermentation and survival of Lactobacillus casei NCDC19 during storage of fermented milk was studied. RESULTS: Among the different cultures screened for ACE inhibitory activity, Lactobacillus casei NCDC 19 exhibited the highest ACE inhibition (approx. 40%) as well as extent of proteolysis (0.37, Abs340). In the presence of Aloe vera (0.5% and 1% w/v) an increase in extent of proteolysis (0.460 ± 0.047 and 0.480 ± 0.027) and percent ACE inhibitory activity (44.32 ± 2.83 and 47.52 ± 1.83) was observed in comparison to control. Aloe vera powder addition also led to an increase in viable counts (>11 log cfu mL⁻¹) of L. casei NCDC 19 in fermented milk during storage for 7 days and the counts were maintained in sufficiently higher numbers. CONCLUSION: The study suggests Aloe vera to be a good functional ingredient which can be further explored for different health attributes.

A systematic review of Gymnema sylvestre in obesity and diabetes management.

The prevalence of obesity is associated with many health-related problems. Currently, more than 300 million people are considered to be obese. According to the World Health Organization (WHO), by 2030, 87 and 439 million people will be affected in India and the world, respectively. Today, herbal medicines are gaining interest in the treatment of obesity and diabetes, because of their minimal side effects. Gymnemic acid - an active component isolated from Gymnema sylvestre - has anti-obesity and antidiabetic properties, decreases body weight and also inhibits glucose absorption. Several components extracted from Gymnema prevent the accumulation of triglycerides in muscle and liver, and also decrease fatty acid accumulation in the circulation. In this paper, an attempt has been made to review the effects of various extracts from Gymnema sylvestre in the regulation of carbohydrate and lipid metabolism in both animal and clinical studies.

Prostate fibroblasts and prostate cancer associated fibroblasts exhibit different metabolic, matrix degradation and PD-L1 expression responses to hypoxia.

Fibroblasts are versatile cells that play a major role in wound healing by synthesizing and remodeling the extracellular matrix (ECM). In cancers, fibroblasts play an expanded role in tumor progression and dissemination, immunosuppression, and metabolic support of cancer cells. In prostate cancer (PCa), fibroblasts have been shown to induce growth and increase metastatic potential. To further understand differences in the functions of human PCa associated fibroblasts (PCAFs) compared to normal prostate fibroblasts (PFs), we investigated the metabolic profile and ECM degradation characteristics of PFs and PCAFs using a magnetic resonance imaging and spectroscopy compatible intact cell perfusion assay. To further understand how PFs and PCAFs respond to hypoxic tumor microenvironments that are often observed in PCa, we characterized the effects of hypoxia on PF and PCAF metabolism, invasion and PD-L1 expression. We found that under normoxia, PCAFs displayed decreased ECM degradation compared to PFs. Under hypoxia, ECM degradation by PFs increased, whereas PCAFs exhibited decreased ECM degradation. Under both normoxia and hypoxia, PCAFs and PFs showed significantly different metabolic profiles. PD-L1 expression was intrinsically higher in PCAFs compared to PFs. Under hypoxia, PD-L1 expression increased in PCAFs but not in PFs. Our data suggest that PCAFs may not directly induce ECM degradation to assist in tumor dissemination, but may instead create an immune suppressive tumor microenvironment that further increases under hypoxic conditions. Our data identify the intrinsic metabolic, ECM degradation and PD-L1 expression differences between PCAFs and PFs under normoxia and hypoxia that may provide novel targets in PCa treatment.

Genetic predisposition for development of nephropathy in type 2 diabetes mellitus.

The aim of the study was to explore the association of the angiotensin-converting enzyme (ACE) gene I/D polymorphism and the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with development of diabetic nephropathy in type 2 diabetes mellitus. Three groups were recruited during 2007-2011: 232 normal controls, 185 type 2 diabetics without nephropathy, and 407 type 2 diabetics with nephropathy. The ACE I/D and MTHFR C677T polymorphisms were examined using PCR and PCR-RFLP methods. We found no significant association of the ACE I/D polymorphism with diabetic nephropathy in genotype, allele, dominant, and recessive models. We observed a significant association of MTHFR C677T with development of diabetic nephropathy in type 2 diabetics. The MTHFR C677T polymorphism plays a significant role in predisposition of renal insufficiency in diabetic patients.

Effect of Lactobacillus acidophilus NCDC 13 supplementation on the progression of obesity in diet-induced obese mice.

There is an increased interest in investigating the relationship between the gut microbiota and energy homeostasis. Probiotics are health beneficial microbes mainly categorised under the genus Lactobacillus and Bifidobacterium, which when administered in adequate amounts confer health benefits to the host, and have been implicated in various physiological functions. The potential role of probiotics in energy homeostasis is a current and an emerging area of research. In the present study, Lactobacillus acidophilus NCDC 13 was used to evaluate its anti-obesity potential in diet-induced obese (C57BL/6) mice. The probiotic bacterial culture was administered in Indian yogurt preparation called 'dahi', prepared using native starter cultures, and compared with control dahi containing only dahi starter cultures. The dietary intervention was followed for 8 weeks, and whole-body fat composition, and liver and muscle adiposity were measured using MRI. Changes in gut microbiota were assessed by fluorescent in situ hybridisation in faeces and caecal contents. The feeding of the probiotic brought no changes in body-weight gain, food and dahi intake when compared with the control dahi-fed animals. No significant changes in body fat composition, liver and muscle adiposity were also observed. At the end of the dietary intervention, a significant increase (P < 0·05) in the number of total Bifidobacterium was observed in both faeces and caecal contents of mice as a result of probiotic dahi administration. Thus, L. acidophilus NCDC 13 supplementation could be beneficial in shifting the gut microbiota balance positively. However, its anti-obesity potential could not be established in the present study and warrants further exploration.