Body Mass Research Articles

Glycemic Control and Body Weight Reduction with Once-Weekly Semaglutide in Colombian Adults with Type 2 Diabetes: Findings from the COLIBRI Study.

Type 2 diabetes is a prevalent condition. The change in glucose control and body weight with the use of once-weekly semaglutide was evaluated in individuals with Type 2 diabetes in Colombia. This was a real-world, multi-centre, single-arm study involving adults in Colombia with Type 2 diabetes treated with once-weekly subcutaneous semaglutide for approximately 26 weeks. The primary endpoint assessed the change in glycated hemoglobin (HbA1c) from baseline to end of study. Secondary endpoints included changes in body weight from baseline to end of study. The study also explored the proportion of participants achieving predefined HbA1c targets and weight-loss responses at the end of the study. Data from 225 patients across 11 centers were collected. Most patients were women (65%), and the mean age of the population was 57 years with a median HbA1c of 7.6% and a median body weight of 86 kg. After approximately 26 weeks, semaglutide was associated with a significant reduction in HbA1c of -0.88 and a body weight reduction of -4.04kg. The proportion of patients with HbA1c < 7% increased from 32 to 66% at end of study. Patients treated with once-weekly semaglutide experienced a clinically significant reduction in HbA1c and body weight. These results are in line with previous clinical trials.

Validity of the Hawkin Dynamics Wireless Dual Force Platform System Against a Piezoelectric Laboratory Grade System for Vertical Countermovement Jump Variables.

Dos'Santos, T, Evans, DT, and Read, DB. Validity of the Hawkin dynamics wireless dual force platform system against a piezoelectric laboratory grade system for vertical countermovement jump variables. J Strength Cond Res 38(6): 1144-1148, 2024-The aim of this study was to determine the criterion validity of the Hawkin Dynamics (HD) wireless dual force platform system for assessing vertical countermovement jump (CMJ) variables, compared with those derived from a Kistler piezoelectric laboratory grade force platform system. During a single testing session, HD force platforms were placed directly on top of 2 adjacent Kistler force platforms to simultaneously collect vertical ground reaction forces produced by 2 male recreational soccer players (age: 29.0 ± 2.8 years, height: 1.79 ± 0.01 m, mass: 85.6 ± 4.7 kg) that performed 25 vertical CMJs each. Sixteen vertical CMJ variables pertaining to jump height (JH), flight time (FT), time-to-take off (TTT), countermovement depth, body weight (BW), propulsive and braking mean, and peak powers, forces, and impulses were compared between systems. Fixed bias was observed for 6 of 16 variables (peak and mean braking power, mean propulsion force, TTT, FT, and BW), while proportional bias was present for 10 of 16 variables (peak and mean propulsive and braking force, TTT, FT, peak and mean braking power, mean propulsive power, and BW). For all variables regardless of fixed or proportional bias, percentage differences were ≤3.4% between force platform systems, with near perfect to perfect correlations (r or ρ = 0.977-1.000) observed for 15 of 16 variables. The HD dual wireless force platform system can be considered a valid alternative to a piezoelectric laboratory grade force platform system for the collection of vertical CMJ variables, particularly outcome (i.e., JH, reactive strength index modified) and strategy variables (countermovement depth).

Population pharmacokinetics and dose rationale for aciclovir in term and pre-term neonates with herpes.

Aciclovir is considered the first-line treatment against Herpes simplex virus (HSV) infections in new-borns and infants. As renal excretion is the major route of elimination, in renally-impaired patients, aciclovir doses are adjusted according to the degree of impairment. However, limited attention has been given to the implications of immature renal function or dysfunction due to the viral disease itself. The aim of this investigation was to characterize the pharmacokinetics of aciclovir taking into account maturation and disease processes in the neonatal population. Pharmacokinetic data obtained from 2 previously published clinical trials (n = 28) were analyzed using a nonlinear mixed effects modeling approach. Post-menstrual age (PMA) and creatinine clearance (CLCR) were assessed as descriptors of maturation and renal function. Simulation scenarios were also implemented to illustrate the use of pharmacokinetic data to extrapolate efficacy from adults. Aciclovir pharmacokinetics was described by a one-compartment model with first-order elimination. Body weight and diagnosis (systemic infection) were statistically significant covariates on the volume of distribution, whereas body weight, CLCR and PMA had a significant effect on clearance. Median clearance varied from 0.2 to 1.0 L/h in subjects with PMA <34 or ≥34 weeks, respectively. Population estimate for volume of distribution was 1.93 L with systemic infection increasing this value by almost 3-fold (2.67 times higher). A suitable model parameterization was identified, which discriminates the effects of developmental growth, maturation, and organ function. Exposure to aciclovir was found to increase with decreasing PMA and renal function (CLCR), suggesting different dosing requirement for pre-term neonates.

Effect of a low-carbohydrate diet on pain and quality of life in female patients with lipedema: a randomized controlled trial.

The primary objective of this study was to evaluate the effect of a low-carbohydrate diet (LCD) compared with a control diet on pain in female patients with lipedema. The secondary objectives were to compare the impact of the two diets on quality of life (QoL) and investigate potential associations of changes in pain with changes in body weight, body composition, and ketosis. Adult female patients with lipedema and obesity were randomized to either the LCD or control diet (energy prescription: 1200 kcal/day) for 8 weeks. Body weight and body composition, pain (Brief Pain Inventory measured pain), and QoL (RAND 36-Item Health Survey [RAND-36], Impact of Weight on Quality of Life [IWQOL]-Lite, and Lymphoedema Quality of Life [LYMQOL]) were measured at baseline and at postintervention. A total of 70 female patients (age, mean [SD], 47 [11] years; BMI 37 [5] kg/m2) were included. The LCD group had greater weight loss (-2.8 kg; 95% CI: -4.1 to -1.0; p < 0.001) and larger reduction in pain now (-1.1; 95% CI: -1.9 to -0.3; p = 0.009) compared with the control group. No association was found between changes in pain now and weight loss. Both groups experienced improvements in several QoL dimensions. Diet-induced weight loss in women with lipedema can improve QoL. An energy-restricted LCD seems to be superior to a standard control diet in reducing pain.

Grafting onto Tomato Rootstocks Improves Outcomes for Dry-farmed Tomato

Vegetable grafting can mitigate the negative effects of drought on crop production. Dry farming, which is the production of crops without irrigation during a dry growing season, can result in lower yields, smaller fruit, and a higher incidence of blossom-end rot (BER), which is a physiological disorder associated with drought stress. To determine the effects of grafting on yield and fruit quality of dry-farmed tomato (Solanum lycopersicum), three years of trials were conducted using different scion–rootstock combinations and ungrafted controls. In 2020, grafting onto rootstocks ‘DRO141TX’ and ‘Fortamino’ resulted in greater total yield and average fruit weight and a lower BER incidence for dry-farmed tomato than grafting onto the rootstock ‘Shincheonggang’ or using ungrafted plants. In 2021, grafting onto the rootstock ‘DRO141TX’ again increased yields and average fruit weight and decreased BER incidence when compared with ungrafted plants (‘Fortamino’ was not tested). Interactions were detected between different scion–rootstock combinations in terms of the degree of reduction of necrotic BER (BER resulting in a large, sunken, grey or black spot, making the fruit unmarketable) when grafted onto ‘DRO141TX’, with the scion ‘Azoychka’ having a 69% reduction in necrotic BER and the scion ‘Astrakhanskie’ having a 93% reduction in necrotic BER. In 2022, an interaction was detected between the rootstocks and scions in terms of their effect on large fruit (&gt;0.33 lb) yield, with ‘BHN 871’ grafted onto ‘Fortamino’ producing the highest yields of large fruit and ‘Big Beef’ grafted onto ‘Fortamino’ producing the lowest yields. Overall, grafting onto the rootstocks ‘DRO141TX’ or ‘Fortamino’ improved diverse dry-farmed tomato outcomes in the Willamette Valley of Oregon, USA.

Characterization of tirzepatide-treated patients achieving different glycemic control levels in SURPASS-AP-Combo.

The study objective was to characterize subgroups of Asia-Pacific patients with type 2 diabetes who achieved different glycated hemoglobin (HbA1c) targets on tirzepatide treatment. This was a post hoc analysis of the SURPASS AP-Combo study. Baseline characteristics, changes in metabolic markers, and safety were compared between tirzepatide-treated patients achieving HbA1c <7.0% (<53 mmol/mol) and those achieving ≥7.0% (≥53 mmol/mol) at week 40. Among patients achieving HbA1c <7.0% (<53 mmol/mol), further comparisons were conducted among subgroups achieving HbA1c <5.7% (<39 mmol/mol), 5.7% to 6.5% (39 to 48 mmol/mol), and >6.5% to <7.0% (>48 to <53 mmol/mol). Five hundred ninety-eight patients on tirzepatide treatment without rescue medication were included (56.9% male; mean age: 53.1 years; mean baseline HbA1c: 8.7% [71.6 mmol/mol]). Patients achieving HbA1c <7.0% (<53 mmol/mol) versus ≥7.0% (≥53 mmol/mol) were slightly younger with a shorter disease duration and lower HbA1c at baseline, and they had greater improvements in HbA1c, fasting serum glucose, body weight, BMI, waist circumference, waist-height ratio, diastolic blood pressure, lipids, and self-monitored blood glucose at week 40. Patients achieving HbA1c <5.7% (<39 mmol/mol) versus those achieving 5.7% to 6.5% (39 to 48 mmol/mol) and those achieving >6.5% to <7.0% (>48 to <53 mmol/mol) were much younger, had much lower HbA1c, and had further improvements in metabolic markers. Tirzepatide treatment was well tolerated irrespective of the HbA1c level achieved, with a low incidence of hypoglycemic events. These findings may help to inform clinical decisions in Asia-Pacific patients with type 2 diabetes.

Once-weekly semaglutide versus placebo in adults with increased fracture risk: a randomised, double-blinded, two-centre, phase 2 trial

Previous studies have indicated that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) may enhance bone formation and have neutral or beneficial effects on fracture risk. We evaluated the effect of the GLP-1RA semaglutide on the bone formation marker Procollagen type I N-terminal propeptide (PINP) in adults with increased fracture risk. This randomised, placebo-controlled, double-blinded, phase 2 clinical trial was conducted at two public hospitals in Denmark. We enrolled 64 men and women with increased fracture risk based on a T-score<-1.0at the total hip or lumbar spine and/or low-energy fracture within three years of recruitment. Participants were randomised (1:1) to receive once-weekly subcutaneous semaglutide 1.0mg or placebo. The primary outcome was changes in plasma (P)-PINP from baseline to week 52. Primary and safety outcomes were assessed and evaluated for all participants. This trial is complete and registered with ClinicalTrials.gov, NCT04702516. Between March 24 and December 8, 2021, 55 (86%) postmenopausal women and nine men with a mean age of 63 years (SD 5.5) and BMI of 27.5kg/m2 (SD 4.5) were enrolled. There was no effect on changes in P-PINP from baseline to week 52 between the two groups (estimated treatment difference (ETD) semaglutide versus placebo 3.8μg/L [95% CI-5.6 to 13.3]; p=0.418), and no difference in P-PINP levels between groups at week 52 (semaglutide 64.3μg/L versus placebo 62.3μg/L [95% CI-10.8 to 15.0]; p=0.749). The secondary outcomes showed higher plasma levels of bone resorption marker Collagen type I cross-linked C-terminal telopeptide (P-CTX) in the semaglutide group than in the placebo group (ETD 166.4ng/L [95% CI 25.5-307.3]; p=0.021). Compared to placebo, lumbar spine and total hip areal bone mineral densities (aBMD) were lower in the semaglutide groupafter 52 weeks ((ETD lumbar spine-0.018g/cm3 [95% CI-0.031 to-0.005]; p=0.007); ETD total hip-0.020g/cm2 ([95% CI-0.032 to-0.008]; p=0.001). Treatment differences in femoral neck aBMD were not observed ([95% CI [-0.017 to 0.006]; p=0.328). Further, body weight was lower in the semaglutide group than in the placebo group after 52 weeks (ETD-6.8kg [95% CI-8.8 to-4.7]; p<0.001). Thirty-one [97%] in the semaglutide group and 18 [56%] in the placebo group experienced at least one adverse event, including four serious events (two in each group). No episodes of hypoglycaemia or deaths were reported. In adults with increased fracture risk, semaglutide once weekly did not increase bone formation based on the bone formation marker P-PINP. The observed increase in bone resorption in the semaglutide group may be explained by the accompanying weight loss. Region of Southern Denmark, Novo Nordisk Foundation, and Gangsted Foundation. Novo Nordisk provided the investigational drug and placebo.

Therapeutic potentials of Hibiscus trionum: Antioxidant, anti-lipid peroxidative, hypoglycemic, and hepatoprotective effects in type 1 diabetic rats

Recent advances in diabetes treatment have primarily focused on insulin and hypoglycemic agents; however, there is growing interest in exploring herbal and synthetic alternatives. Numerous studies have highlighted the preventive effectiveness of regular plant consumption in managing chronic conditions, particularly diabetes. Hibiscus, a medicinal plant recognized in various cultures, is known for its diverse health benefits. This study investigated the impact of Hibiscus trionum on glycemic control and assessed its influence on glucose and insulin levels in diabetes-induced rats. The concentrations of antioxidant enzymes, particularly superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were scrutinized across multiple body tissues (plasma, heart, muscle, liver, and kidney). The malondialdehyde (MDA) concentration, an indicator of lipid peroxidation, was examined in both plasma and tissue samples. Serum total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were evaluated. Diabetic Group (D) exhibited a significant decrease in body weight, increased fluid and food consumption, elevated blood glucose levels, and increased antioxidant enzyme activity. Moreover, the diabetic group also showed increased levels of MDA, TC, TG, AST, and ALT, along with reduced insulin levels, compared to the control group. A substantial improvement in all parameters impaired by diabetes was observed following the application of Hibiscus trionum (HTT) in the Diabetes+HTT group. The antioxidative stress-reducing, lipid peroxidation-improving, and hepatoprotective potential of Hibiscus trionum in mitigating diabetes-induced oxidative stress is noteworthy. These findings indicate that HTT supplementation has valuable beneficial effects in protecting against the harmful impacts of diabetes.

Internet of things-based digital scale to detect stunting symptoms in babies under two years of age

Given the ongoing global challenge of stunting, characterized primarily by chronic underweight in infants under two years of age, a new approach leveraging digital scale and the internet of things (IoT) has been developed. This innovative system was designed to facilitate the early detection and continual monitoring of stunting symptoms caused by malnourishment. Key features include an IoT-enabled digital scale for precise weight measurement, a robust cloud platform for reliable data storage and comprehensive analysis, and an easy-to-use mobile app for user engagement. This system demonstrates its potential to simplify tracking fluctuations in baby weight and development progress related to stunting over time. Early trials demonstrated an impressive accuracy rate of 99.4% in body weight measurements and provided excellent conclusions in determining the body weight status of the infants. Overall, this IoT-based solution catalyzes the improvement of stunting detection methodologies and early intervention strategies, thus promising a better solution and a significant positive impact on global child health.

A novel dosing approach for rituximab in glomerular diseases based on a population pharmacokinetic analysis

ObjectivesRituximab is being increasingly prescribed for the treatment of autoimmune glomerular diseases. While it is highly effective for some diseases, the response is less predictable for others, which may be due to differing requirements in terms of the dosing according to the disease type and variations concerning exposure to the drug. MethodsWe compiled novel rituximab dosing schedules according to pharmacokinetic analysis of data gathered from rituximab treated patients in a tertiary referral nephrology centre between May 2020 and June 2023. The population-pharmacokinetic analysis was based on the rituximab dosing, the patients’ characteristics, rituximab levels and anti-rituximab antibodies. ResultsThe analysis, which was based on data from 185 patients, clearly highlighted differing rituximab dosing requirements for patients with ANCA associated vasculitis and minimal change disease compared to those with membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This corresponded to the good treatment response of the first two diseases and the unreliable efficacy for the others. The model predicts the rituximab pharmacokinetics with high degree of accuracy when body weight, proteinuria, type of glomerulonephritis, treatment length and anti-rituximab antibodies formation are used as covariates. We proposed a dosing schedule with shortened dosing intervals for difficult-to-treat diagnoses with high proteinuria. ConclusionIn order to ensure reliable and comparable exposure of rituximab with respect to the full range of glomerular diseases, the dosing schedule should be adjusted for membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This is largely, but not solely, due to the enhanced level of unselective proteinuria in these diseases.

Tetrabromobisphenol A reduces male rats reproductive organ coefficients and disrupting sexual hormone by causing oxidative stress

Tetrabromobisphenol A (TBBPA) has become a topic of public attention due to its pervasive detection in the environment and organisms in recent decades. However, limited information is available regarding the toxicity of TBBPA on reproductive ability of male mammals. Herein, the reproductive toxicity of TBBPA was investigated in male rats to fill the knowledge gap. In this study, male rats were exposed to TBBPA (0, 10, 100, and 1000mg/kg) for 6 weeks. Subsequently, body and organ indexes, histopathological evaluation of testis and epididymis, ultrastructural observation of sperm, testosterone and progesterone levels, and oxidative stress indicators were conducted to reveal corresponding mechanisms. Results obtained showed that compare to the control group, the body weight, testes weight, epididymis weight, seminal vesicle and coagulation glands weight of rats in the 1000mg/kg group lost 8.30%, 16.84%, 20.16%, 19.72% and 26.42%, respectively. Intriguingly, exposure to TBBPA (10, 100, 100mg/kg) resulted in substantial pathological damage in testis, epididymis and sperm. TBBPA exposure also increased malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents, as well as superoxide dismutase (T-SOD) and catalase (CAT) activities in testicular tissue. What’s more, the testosterone and progesterone levels in male rat serum were significantly decreased after exposure to TBBPA for 6 weeks. Meanwhile, results of molecular docking showed that TBBPA has a strong affinity with estrogen receptors (ERs). These findings demonstrated that TBBPA exposure negatively impacts the reproductive ability of male rats, thus providing new insights for risk assessment for reproductive health under TBBPA exposure.

Use of Mesenchymal Stem Cells in Experimental Ovarian Damage.

Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamicpituitary- gonadal axis. The current study investigated the therapeutic potentials of mesenchymal stem cells (MSCs) in a murine model of BPA-induced ovarian damage. Fifty adult female rats were divided into: Group 1; control group, Group IIa, IIb: rats were given oral gavage of BPA (25 and 50 mg/Kg body weight respectively) on a daily basis for 15 days, and Group IIIa, IIIb; rats were intravenously treated with of MSCs (106 cells) after receiving the last dose of BPA as in group II. Plasma and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). A histological examination of ovarian tissue was also conducted. BPA resulted in a significant elevation in plasma levels of LH, FSH, and ovarian tissue levels of MDA and a significant decrease in estradiol and progesterone. All genetic and protein markers of apoptosis were elevated in BPA treated group with decreased oestrogen receptor expression in the ovarian tissue. Increased apoptotic cells were confirmed by TUNEL assay. A high dose of BPA was able to increase the number of atretic follicles in the ovarian tissue whereas the numbers of primordial, primary, secondary and Graafian follicles were decreased. All the laboratory and histological abnormalities were ameliorated by treatment with MSCs. The antioxidant and anti-apoptotic effects of MSCs could possibly explain the ability of this therapeutic modality to ameliorate BPA-induced-ovarian damage.

Effects of Saikosaponin D on Apoptosis, Autophagy, and Morphological Structure of Intestinal Cells of Cajal with Functional Dyspepsia.

Functional dyspepsia (FD) is one of the most common gastrointestinal diseases, with a global prevalence of 10%-30%. However, the specific pathogenesis of FD has not yet been determined. As such, the aim of this study was to investigate the effects of saikosaponin D (SSD) administration on the apoptosis, autophagy, and morphological structure of the intestinal cells of Cajal (ICCs) in FD. Methods：A rat model of FD was constructed by stimulating the rat tail with a sponge clamp at one-third of the distal tail length. An autophagy model was constructed for ICCs using glutamate. The apoptosis rate in each group of cells was determined using flow cytometry. The expressions of ghrelin and substance P (SP) were detected using ELISA. The body weight and food intake of male and female rats in the SSD group were consistently higher than those in the model group. The SSD group showed substantial improvement compared with the model group, with no inflammatory cell infiltration and normal gastric mucosal structures. After intervention with SSD, the ultrastructure of the ICCs considerably improved and was clear. Compared with the model group, the expressions of LC3 I/II, ghrelin, and SP proteins in the SSD group were significantly upregulated, and the apoptosis rate was significantly reduced. The administration of SSD improved ICC morphology and structure, inhibited excessive autophagy, and improved FD, a gastrointestinal motility disorder, by regulating ghrelin and SP levels.

MicroRNA-29-mediated cross-talk between metabolic organs in the pathogenesis of diabetes mellitus and its complications: A narrative review.

Diabetes mellitus (DM) is a heterogeneous group of disorders characterized by hyperglycemia. Microribonucleic acids (microRNAs) are noncoding RNA molecules synthesized in the nucleus, modified, and exported to the extracellular environment to bind to their complementary target sequences. It regulates protein synthesis in the targeted cells by inhibiting translation or triggering the degradation of the target messenger. MicroRNA-29 is one of noncoding RNA that can be secreted by adipose tissue, hepatocytes, islet cells, and brain cells. The expression level of the microRNA-29 family in several metabolic organs is regulated by body weight, blood concentrations of inflammatory mediators, serum glucose levels, and smoking habits. Several experimental studies have demonstrated the effect of microRNA-29 on the expression of target genes involved in glucose metabolism, insulin synthesis and secretion, islet cell survival, and proliferation. These findings shed new light on the role of microRNA-29 in the pathogenesis of diabetes and its complications, which plays a vital role in developing appropriate therapies. Different molecular pathways have been proposed to explain how microRNA-29 promotes the development of diabetes and its complications. However, to the best of our knowledge, no published review article has summarized the molecular mechanism of microRNA-29-mediated initiation of DM and its complications. Therefore, this narrative review aims to summarize the role of microRNA-29-mediated cross-talk between metabolic organs in the pathogenesis of diabetes and its complications.

Effects of some locally isolated Lactobacillus species on general growth, muscular mass and bone development in mice

Probiotics are dietary supplements which contain live microorganisms, mostly different bacterial species that inhabit gut of host and ultimately benefit that host. The current investigation was done to explore the growth-promoting effects of four locally isolated probiotics strains L. paracasei, L. paracaseii, L. delbrueckii and L. rhamnosus. In this regard, 108 colony-forming units (CFU) were administered to the mice of experimental groups for 30 days. Upon administering probiotics, it was observed that the Lactobacilli species had a positive impact on body weight. The group that received L. rhamnosus exhibited the most significant increase, with a 76.53 % improvement over the control group (P < 0.05). Positive effects on somatic indices of different organs including spleen, thymus, kidneys, heart, liver, and lungs were also observed. In addition to all of these, the increases in the number of extensor digitorum longus (EDL) muscle fibers and their cross-sectional area (CSA) up to 40.70 % and 28.94 % respectively in L. rhamnosus group as compared with the control group. In the L. rhamnosus group, there was a 40.70 % increase in the number of EDL muscle fibers and a 28.94 % increase in their cross-sectional area (CSA) of muscle fiber as compared to the control group. On provision of Lacticaseibacillus rhamnosus, 50.81 % higher femur bone density was noted which endorse the overall health-improving abilities of this probiotic. The application of Lacticaseibacillus rhamnosus in animal feed is recommended.

Optimized new Shengmai powder inhibits myocardial fibrosis in heart failure by regulating the rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway.

Exploring the effect of Optimized New Shengmai powder (, ONSMP) on myocardial fibrosis in heart failure (HF) based on rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinases (ERK) signaling pathway. Randomized 70 Sprague-Dawley rats into sham (n = 10) and operation (n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low (L), medium (M), and high (H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat's body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen (COL) I and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the mRNA levels of COL I, COL Ⅲ, α-smooth muscle actin (α-SMA), and c-Fos proto-oncogene (c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor (p-ELK1), p-c-Fos, α-SMA, COL I, and COL Ⅲ by Western blot. ONSMP can effectively improve HF rat's cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL I/Ⅲ content, down-regulate the mRNA of COL I/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/ 2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA. ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.

Elucidation of novel drought-responsive genes from tuber transcriptome of cassava under water deficit stress

Cassava (Manihot esculenta Carntz) is the major starchy root crop grown in the tropical parts of the world. Two cassava clones contrasting for their drought tolerance capacity (8S501- drought tolerant and H97-drought sensitive) were selected and grown in the field for studying the agronomical and molecular changes in both the clones under drought stress conditions. A reduction in the number of tuberous roots per plant, tuberous root length, average single tuber weight and tuber yield per plant was observed under drought stress when compared with the control conditions and also significantly lower mean values were observed for the sensitive clone H97 than that of the tolerant clone 8S501 when measured at 60 days of stress. Transcriptome sequencing of the tuber tissues of the two clones was done at 60 days of imposing drought stress. Different genes belonging to various groups like aquaporins, transporter genes, growth regulator related genes, calcium binding and mineral transfer-related genes, transferase genes and transcription factors were differentially expressed in the tubers under drought stress. Comparative transcriptomics revealed that acyl-CoA oxidase, primary-amine oxidase, glutathione peroxidase, vesicle transport, late embryogenesis abundant protein related, histone demethylase, BR-signaling kinase, palmitoyltransferase, DNA mismatch repair protein, heat shock protein related, starch/sucrose metabolic pathway related and MFS transporter genes were differentially expressed in the tubers of the tolerant clone 8S501 relative to the susceptible clone H97.

Phase 1 Study of CK0801 in Treatment of Bone Marrow Failure Syndromes.

An inflammatory bone marrow microenvironment contributes to acquired bone marrow failure syndromes. CK0801, an allogeneic T regulatory (Treg) cell therapy product, can potentially interrupt this continuous loop of inflammation and restore hematopoiesis. In this phase 1 dose-escalation study of CK0801 Treg cells, we enrolled patients with bone marrow failure syndromes with suboptimal response to their prior therapy to determine the safety and efficacy of this treatment for bone marrow failure syndromes. We enrolled nine patients with a median age of 57 years (range, 19 to 74) with an underlying diagnosis of aplastic anemia (n=4), myelofibrosis (n=4), or hypoplastic myelodysplasia (n=1). Patients had a median of three prior therapies for a bone marrow failure syndrome. Starting dose levels of CK0801 were 1 × 106 (n=3), 3 × 106 (n=3), and 10 × 106 (n=3) cells per kg of ideal body weight. No lymphodepletion was administered. CK0801 was administered in the outpatient setting with no infusion reactions, no grade 3 or 4 severe adverse reactions, and no dose-limiting toxicity. At 12 months, CK0801 induced objective responses in three of four patients with myelofibrosis (two had symptom response, one had anemia response, and one had stable disease) and three of four patients with aplastic anemia (three had partial response). Three of four transfusion-dependent patients at baseline achieved transfusion independence. Although the duration of observation was limited at 0.9 to 12 months, there were no observed increases in infections, no transformations to leukemia, and no deaths. In previously treated patients, CK0801 demonstrated no dose-limiting toxicity and showed evidence of efficacy, providing proof of concept for targeting inflammation as a therapy for bone marrow failure. (Funded by Cellenkos Inc.; Clinicaltrials.gov number, NCT03773393.).

A Prerequisite for need of Harmonized Nutrient Reference Values &amp; its Standardized Terminology for Better access of Nutritional Supplements Globally

Abstract: To reduce the risk of insufficient nutrient intake, nutrient reference values for humans are set at the average nutrient need level without a safety margin. The vast majority of nations and areas in the globe set nutritional intake guidelines for their citizens. Currently, no harmonized nutrient reference value has been published, as well as the development of standards cannot be achieved through the use of formalized frameworks or terminology. The study's objective was to create recommendations for appropriate and secure micronutrient intake ranges that could be used to inform dietary advice. As relevant to the study, we examined micronutrient data from food intake surveys from representative nations. The comparison of national standards illustrates that the level of reference values for nutrient for individual countries is dependent on variables such as methodology, data sources, physical activity exemptions, standard body weights, and age range. In the current study, iron, calcium, magnesium, vitamin A, B12, D and folate were identified as the most commonly under-consumed micronutrients. In this article, the level of six countries' standards are compared to the current reference values for nutrients. Further, numerous words for different dietary standards components are discussed, and a final set of harmonized reference nutrient intake for the dietary advice is provided.

Association between insulin sensitivity and lean mass loss during weight loss.

The study objective was to assess the relationship between insulin sensitivity and changes in total lean mass (LM) and appendicular LM (ALM) during weight loss. Individuals were randomly assigned to either a standard or a moderately reduced carbohydrate diet for 16 weeks. Body composition was assessed using dual-energy x-ray absorptiometry and insulin sensitivity index (SI) using an intravenous glucose tolerance test. Multiple linear regression was used to determine whether baseline SI was predictive of changes in total LM and ALM. Participants (n = 57; baseline BMI 32.1 ± 3.8 kg/m2) lost an average of 6.8 ± 3.2 kg of body weight (p < 0.001), with 1.5 ± 2.6 kg coming from LM (p < 0.05) and 0.5 ± 0.73 kg from ALM (p < 0.05). Multiple regression analysis demonstrated that SI was inversely associated with changes in total LM (kilograms; β = 0.481, p < 0.001), after adjusting for baseline LM, fat mass, acute insulin response to glucose, and weight loss. Similar results were seen when assessing ALM loss (β = 0.359, p < 0.05). Identifying individuals with low insulin sensitivity prior to weight loss interventions may allow for a personalized approach aiming at minimizing LM loss.