Pericardial Adipose Tissue Thrombospondin-1 Associates With Antiangiogenesis in Ischemic Heart Disease.

Accumulation of ectopic pericardial adipose tissue has been associated with cardiovascular complications which, in part, may relate to adipose-derived factors that regulate vascular responses and angiogenesis. We sought to characterize adipose tissue microvascular angiogenic capacity in subjects who underwent elective cardiac surgeries including aortic, valvular, and coronary artery bypass grafting. Pericardial adipose tissue was collected intraoperatively and examined for angiogenic capacity. Capillary sprouting was significantly blunted (twofold, p <0.001) in subjects with coronary artery disease (CAD) (age 60 ± 9 years, body mass index [BMI] 32 ± 4 kg/m2, low-density lipoprotein cholesterol [LDL-C] 95 ± 46 mg/100 ml, n = 29) compared with age-, BMI-, and LDL-C matched subjects without angiographic obstructive CAD (age 59 ± 10 y, BMI 35 ± 9 kg/m2, LDL-C 101 ± 40 mg/100 ml, n = 12). For potential mechanistic insight, we performed mRNA expression analyses using quantitative real-time polymerase chain reaction and observed no significant differences in pericardial fat gene expression of proangiogenic mediators vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor-2 (FGF-2), and angiopoietin-1 (angpt1), or anti-angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and endostatin. In contrast, mRNA expression of anti-angiogenic thrombospondin-1 (TSP-1) was significantly upregulated (twofold, p = 0.008) in CAD compared with non-CAD subjects, which was confirmed by protein western-immunoblot analysis. TSP-1 gene knockdown using short hairpin RNA lentiviral delivery significantly improved angiogenic deficiency in CAD (p <0.05). In conclusion, pericardial fat in subjects with CAD may be associated with an antiangiogenic profile linked to functional defects in vascularization capacity. Local paracrine actions of TSP-1 in adipose depots surrounding the heart may play a role in mechanisms of ischemic heart disease.

Descriptive analyses of bacterial communities in marine sediment microcosms spiked with fish wastes, emamectin benzoate, and oxytetracycline.

In marine sediments surrounding salmon aquaculture sites, organic matter (OM) enrichment has been shown to influence resident bacterial community composition; however, additional effects on these communities due to combined use of the sea-lice therapeutant emamectin benzoate (EMB) and the widely used antibiotic oxytetracycline (OTC) are unknown. Here, we use sediment microcosms to assess the influence of OM, EMB, and OTC on benthic bacterial communities. Microcosms consisted of mud or sand sediments enriched with OM (fish and feed wastes) and spiked with EMB and OTC at environmentally-relevant concentrations. Samples were collected from initial matrices at the initiation of the trial and after 110 days for 16 S rRNA gene sequencing of the V3-V4 region and microbiome profiling. The addition of OM in both mud and sand sediments reduced alpha diversities; for example, an average of 1106 amplicon sequence variants (ASVs) were detected in mud with no OM addition, while only 729 and 596 ASVs were detected in mud with low OM and high OM, respectively. Sediments enriched with OM had higher relative abundances of Spirochaetota, Firmicutes, and Bacteroidota. For instance, Spirochaetota were detected in sediments with no OM with a relative abundance range of 0.01-1.2%, while in sediments enriched with OM relative abundance varied from 0.16% to 26.1%. In contrast, the addition of EMB (60 ng/g) or OTC (150 ng/g) did not result in distinct taxonomic shifts in the bacterial communities compared to un-spiked sediments during the timeline of this experiment. EMB and OTC concentrations may have been below effective inhibitor concentrations for taxa in these communities; further work should explore gene content and the presence of antibiotic resistance genes (ARGs) in sediment-dwelling bacteria.

Enhanced production of select phytocannabinoids in medical Cannabis cultivars using microbial consortia.

The root microbiome of medical cannabis plants has been largely unexplored due to past legal restrictions in many countries. Microbes that live on and within the tissue of Cannabis sativa L. similar to other plants, provide advantages such as stimulating plant growth, helping it absorb minerals, providing protection against pathogen attacks, and influencing the production of secondary metabolites. To gain insight into the microbial communities of C. sativa cultivars with different tetrahydrocannabinol (THC) and cannabidiol (CBD) profiles, a greenhouse trial was carried out with and without inoculants added to the growth substrate. Illumina MiSeq metabarcoding was used to analyze the root and rhizosphere microbiomes of the five cultivars. Plant biomass production showed higher levels in three of five cultivars inoculated with the arbuscular mycorrhizal fungus Rhizophagus irregularis and microbial suspension. The blossom dry weight of the cultivar THE was greater when inoculated with R. irregularis and microbial suspension than with no inoculation. Increasing plant biomass and blossom dry weight are two important parameters for producing cannabis for medical applications. In mature Cannabis, 12 phytocannabinoid compounds varied among cultivars and were affected by inoculants. Significant differences (p ≤ 0.01) in concentrations of cannabidivarinic acid (CBDVA), cannabidivarin (CBDV), cannabigerol (CBG), cannabidiol (CBD), and cannabigerolic acid (CBGA) were observed in all Cannabis cultivars when amended with F, K1, and K2 inoculants. We found microbes that were shared among cultivars. For example, Terrimicrobium sp., Actinoplanes sp., and Trichoderma reesei were shared by the cultivars ECC-EUS-THE, CCL-ECC, and EUS-THE, respectively. Actinoplanes sp. is a known species that produces phosphatase enzymes, while Trichoderma reesei is a fungal train that produces cellulase and contributes to organic matter mineralization. However, the role of Terrimicrobium sp. as an anaerobic bacterium remains unknown. This study demonstrated that the use of inoculants had an impact on the production of phytocannabinoids in five Cannabis cultivars. These inoculants could have useful applications for optimizing cannabis cultivation practices and increasing the production of phytocannabinoids.

Ultrasonic-assisted sustainable extraction and dyeing of organic cotton fabric using natural dyes from Dillenia indica leaf.

As a means of preventing environmental damage caused by synthetic dyes, eco-friendly textile dyeing with natural dyes is gaining popularity worldwide. This study focused on the extraction of dyes from the leaf of Dillenia indica (D. indica) tree using an ultrasonic extraction technique and applied on the organic cotton fabrics. The ultrasonic method was used for both extractions of D. indica dyes and dyeing of organic cotton fabrics. Here, the amount of D. indica powder used were 5% and 6.67% for producing light and dark shade, respectively. The investigation of the color fastness to washing, rubbing, and light for the dyed organic cotton fabrics indicated an excellent rating. The spectrophotometric analysis revealed the L* (lightness or darkness), a* (redness or greenness), b* (yellowness or blueness), C* (chroma), h* (hue), R% (reflectance), and K/S (color strength) values, which accurately represented the shade of the dyed organic cotton fabric. To understand the interaction between D. indica dye and organic cotton fabrics, different characterization including, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were performed. The characterization outcomes confirmed the successful deposition of D. indica dyes on the organic cotton fabrics. The other comparable testing results such as bursting strength, air permeability, and thermogravimetric analysis (TGA) of dyed and undyed organic cotton fabrics were in the acceptable range. One of the important findings of this research was no chemicals were utilized during the extraction and dyeing of organic cotton fabrics. This process can be referred to as completely chemical-free and advantageous for the environment because no chemicals were needed during extraction or dyeing. Therefore, the natural dye extracted from D. indica is extremely promising and could be a viable option for the sustainable dyeing of cotton fabrics in the textile dyeing industry.

Engineered colorectal cancer tissue recapitulates key attributes of a patient-derived xenograft tumor line.

The development of physiologically relevantin vitrocolorectal cancer (CRC) models is vital for advancing understanding of tumor biology. Although CRC patient-derived xenografts (PDXs) recapitulate key patient tumor characteristics and demonstrate high concordance with clinical outcomes, the use of thisin vivomodel is costly and low-throughput. Here we report the establishment and in-depth characterization of anin vitrotissue-engineered CRC model using PDX cells. To form the 3D engineered CRC-PDX (3D-eCRC-PDX) tissues, CRC PDX tumors were expandedin vivo, dissociated, and the isolated cells encapsulated within PEG-fibrinogen hydrogels. Following PEG-fibrinogen encapsulation, cells remain viable and proliferate within 3D-eCRC-PDX tissues. Tumor cell subpopulations, including human cancer and mouse stromal cells, are maintained in long-term culture (29 days); cellular subpopulations increase ratiometrically over time. The 3D-eCRC-PDX tissues mimic the mechanical stiffness of originating tumors. Extracellular matrix protein production by cells in the 3D-eCRC-PDX tissues resulted in approximately 57% of proteins observed in the CRC-PDX tumors also being present in the 3D-eCRC-PDX tissues on day 22. Furthermore, we show congruence in enriched gene ontology molecular functions and Hallmark gene sets in 3D-eCRC-PDX tissues and CRC-PDX tumors compared to normal colon tissue, while prognostic Kaplan-Meier plots for overall and relapse free survival did not reveal significant differences between CRC-PDX tumors and 3D-eCRC-PDX tissues. Our results demonstrate high batch-to-batch consistency and strong correlation between ourin vitrotissue-engineered PDX-CRC model and the originatingin vivoPDX tumors, providing a foundation for future studies of disease progression and tumorigenic mechanisms.

Higher HbA1c was observed in young people with diabetes who fasted during COVID-19 pandemic lockdown of 2020 Ramadan in Bangladesh - A Post Ramadan survey.

OBJECTIVE: Muslim people with T1DM should be actively discouraged from fasting during the COVID-19 pandemic, as diabetes has emerged as a significant risk factor for adverse outcomes of COVID-19 infection. We report the experience of young patients with type 1, type 2 and other types diabetes who fasted during Ramadan 2020 at the time of the COVID-19 pandemic time lockdown. RESEARCH DESIGN AND METHODS: A Post- Ramadan survey was designed for young patients who fasted during Ramadan in 2020 during COVID pandemic time. The study was conducted to compared the basal characteristics and other parameters in children and adolescents (<18 years), with young adults (≥18 years) with diabetes at Paediatric Diabetes Center in BIRDEM in Bangladesh. RESULTS: Among the study participants, a significantly higher number of participants were in older age group who fasted for more than 15 days (p = 0.045). A considerable proportion (30.7%) of patients developed mild hypoglycaemia, and only eight patients (2.6%) developed moderate to severe hypoglycemia. There was significant reduction of post Ramadan basal insulin dose in both groups (p = 0.001). Although increased bolus insulin dose requirements were observed in older age group, but decreased requirement was observed in younger age group during Ramadan (p = 0.001). Post Ramadan median HbA1C in both groups was increased with marked increase in older age group compared to younger age group though it did not reach the statistical significance. (p = 0.239) CONCLUSIONS: COVID-19 pandemic had minor impact on fasting during Ramadan in our cohort, they could fast safely with less complications during Ramadan. Our data supports Ramadan focused diabetes education with ample self-care, young people with diabetes can fast safely during Ramadan.

Vitamin D status in children and adolescents with type 1 diabetes in a specialized diabetes care centre in Bangladesh.

OBJECTIVES: High prevalence of vitamin D deficiency (VDD) in children and adolescents with type 1 diabetes (T1D) was found in several epidemiological studies. The current study aimed to assess the Vitamin D status in children and adolescents with T1D and to examine the influence of the disease characteristics on vitamin D status in a specialized care centre in a tertiary hospital in Bangladesh. METHODS: Participants were enrolled in the cross-sectional study at the time of a regularly scheduled visit to the CDiC Paediatric Diabetes Center in BIRDEM 2(Bangladesh Institute of Research and Rehabilitation of Diabetes Endocrine and Metabolic Disorders), a tertiary care hospital in Bangladesh. The demographic and clinical data were collected through medical records with a structured questionnaire. RESULTS: Among sixty study participants, most had inadequate levels of vitamin D: deficiency 31 (51.7%), insufficiency 14 (23.3%) and sufficiency 15 (25.0%). Participants with vitamin D deficiency (VDD) were significantly older compared to the sufficient and insufficient group (p = .029), and were residing in urban areas (p = .036) and from higher socioeconomic status (p = .014). BMI was significantly higher in VDD compared to the sufficient group (p = .040). Although we observed higher median values of daily insulin requirements and HbA1c values in patients with VDD compared to patients with vitamin D insufficiency or vitamin D sufficiency, these differences did not reach statistical significance. CONCLUSIONS: The present study revealed that the prevalence of vitamin D deficiency and insufficiency among T1 diabetes children was very high. Future studies in large sample are required to assess hypovitaminosis D in youth with T1D and also the possible relating factors of vitamin D deficiency.

Transcription dynamics of heat-shock proteins (Hsps) and endosymbiont titres in response to thermal stress in whitefly, Bemisia tabaci (Asia-I).

The sweet potato whitefly, Bemisia tabaci (Gennadius), is one of the several species complexes of whitefly that are currently significant agricultural pests. Bemisia tabaci infests more than 600 plant species and thrives under a wide range of temperature conditions. In addition to the direct damage caused by sucking plant sap, it vectors several plant viruses. Heat-shock proteins play a pivotal role in enabling the insect to extend its geographical location, survival, and reproduction under different stress conditions. B. tabaci harbours several endosymbionts under the genera Portiera, Rickettsia, Hamiltonella, Wolbachia, Arsenophonus, Cardinium, and Fritschea that directly or indirectly affect its fitness. By accelerating cuticle biosynthesis and sclerotisation, symbiotic microbes can reduce or enhance tolerance to extreme temperatures and detoxify heavy metals. Thus, symbionts or microbial communities can expand or constrain the abiotic niche space of their host and affect its ability to adapt to changing conditions. The present study delineates the effect of thermal stress on the expression of heat-shock genes and endosymbionts in B. tabaci. Studies of the expression level of heat-shock proteins with the help of quantitative real-time polymerase chain reaction (qRT-PCR) showed that heat- and cold-shock treatment fuels the increased expression of heat-shock proteins (Hsp40 and Hsp70). However, Hsp90 was not induced by a heat- and cold-shock treatment. A significant decrease in the relative titre of secondary endosymbionts, such as Rickettsia, Arsenophonus, and Wolbachia, were recorded in B. tabaci upon heat treatment. However, the titre of the primary symbiont, C. Portiera, was relatively unaffected by both cold and heat treatments. These results are indicative of the fact that Hsp genes and endosymbionts in B. tabaci are modulated in response to thermal stress, and this might be responsible for the adaptation of whitefly under changing climatic scenario.

DeepAProt: Deep learning based abiotic stress protein sequence classification and identification tool in cereals.

The impact of climate change has been alarming for the crop growth. The extreme weather conditions can stress the crops and reduce the yield of major crops belonging to Poaceae family too, that sustains 50% of the world's food calorie and 20% of protein intake. Computational approaches, such as artificial intelligence-based techniques have become the forefront of prediction-based data interpretation and plant stress responses. In this study, we proposed a novel activation function, namely, Gaussian Error Linear Unit with Sigmoid (SIELU) which was implemented in the development of a Deep Learning (DL) model along with other hyper parameters for classification of unknown abiotic stress protein sequences from crops of Poaceae family. To develop this models, data pertaining to four different abiotic stress (namely, cold, drought, heat and salinity) responsive proteins of the crops belonging to poaceae family were retrieved from public domain. It was observed that efficiency of the DL models with our proposed novel SIELU activation function outperformed the models as compared to GeLU activation function, SVM and RF with 95.11%, 80.78%, 94.97%, and 81.69% accuracy for cold, drought, heat and salinity, respectively. Also, a web-based tool, named DeepAProt (http://login1.cabgrid.res.in:5500/) was developed using flask API, along with its mobile app. This server/App will provide researchers a convenient tool, which is rapid and economical in identification of proteins for abiotic stress management in crops Poaceae family, in endeavour of higher production for food security and combating hunger, ensuring UN SDG goal 2.0.

Microbiome of Field Grown Hemp Reveals Potential Microbial Interactions With Root and Rhizosphere Soil.

Hemp (Cannabis sativa L.) is a crop bred and grown for the production of fiber, grain, and floral extracts that contribute to health and wellness. Hemp plants interact with a myriad of microbiota inhabiting the phyllosphere, endosphere, rhizoplane, and rhizosphere. These microbes offer many ecological services, particularly those of below ground biotopes which are involved in nutrient cycling, uptake, and alleviating biotic and abiotic stress. The microbiota communities of the hemp rhizosphere in the field are not well documented. To discover core microbiota associated with field grown hemp, we cultivated single C. sativa cultivar, "TJ's CBD," in six different fields in New York and sampled hemp roots and their rhizospheric soil. We used Illumina MiSeq amplicon sequencing targeting 16S ribosomal DNA of bacteria and ITS of fungi to study microbial community structure of hemp roots and rhizospheres. We found that Planctobacteria and Ascomycota dominated the taxonomic composition of hemp associated microbial community. We identified potential core microbiota in each community (bacteria: eight bacterial amplicon sequence variant - ASV, identified as Gimesia maris, Pirellula sp. Lacipirellula limnantheis, Gemmata sp. and unclassified Planctobacteria; fungi: three ASVs identified as Fusarium oxysporum, Gibellulopsis piscis, and Mortierella minutissima). We found 14 ASVs as hub taxa [eight bacterial ASVs (BASV) in the root, and four bacterial and two fungal ASVs in the rhizosphere soil], and 10 BASV connected the root and rhizosphere soil microbiota to form an extended microbial communication in hemp. The only hub taxa detected in both the root and rhizosphere soil microbiota was ASV37 (Caulifigura coniformis), a bacterial taxon. The core microbiota and Network hub taxa can be studied further for biocontrol activities and functional investigations in the formulation of hemp bioinoculants. This study documented the microbial diversity and community structure of hemp grown in six fields, which could contribute toward the development of bioinoculants for hemp that could be used in organic farming.

Effect of neutralizers and silicone softeners on phenolic yellowing phenomenon of OBA treated cotton knitted fabric.

Phenolic yellowing is a complex physicochemical phenomenon of cotton, especially for white and pastel-colored fabrics. This study tried to analyze the effect of neutralizers and silicone softeners on this. Three types of neutralizers of different chemical characteristics (acetic acid, citric acid, and commercial complex acid) were used to achieve core neutralization whereas two unlike ionic nature of silicone softeners (cationic & non-ionic) for the finishing process used. The acetic acid and nonionic softener treated fabric gives the maximum CIE (International Commission on Illumination) whiteness index value of 151 while citric acid and cationic softener have the least rating of 140.93 with a similar chemical dosage of 1.5 g/l by immediate testing. However, after repeated testing for one-month conditioning in atmospheric conditions, complex acid, and nonionic softener treated samples exhibited the maximum whiteness index of 145.86; on the other hand, citric acid and cationic softener treated one had the least rating of 125.85. Moreover, fabric core pH, reading was found to be 6.68, 6.15 & 5.13 for acetic acid, citric acid, and complex acid through immediate testing. After one month of conditioning, the values were 7.2, 6.61, and 5.25, respectively. Finally, a maximum phenolic yellowing rating of 4-5 was found with complex acid & nonionic softener in contrast poor rating of 2 with acetic acid & cationic softener for immediate testing. Storage of the samples has a significant impact on phenolic yellowing for all types of chemical concentrations. Lightfastness rating was found identical for all samples while bursting strength had a very negligible impact, Fourier transform infrared (FT-IR) spectroscopy also revealed the presence of noticeable chemical functional groups.

Phytate and Microbial Suspension Amendments Increased Soybean Growth and Shifted Microbial Community Structure.

Phytate represents an organic pool of phosphorus in soil that requires hydrolysis by phytase enzymes produced by microorganisms prior to its bioavailability by plants. We tested the ability of a microbial suspension made from an old growth maple forest's undisturbed soil to mineralize phytate in a greenhouse trial on soybean plants inoculated or non-inoculated with the suspension. MiSeq Amplicon sequencing targeting bacterial 16S rRNA gene and fungal ITS was performed to assess microbial community changes following treatments. Our results showed that soybean nodulation and shoot dry weight biomass increased when phytate was applied to the nutrient-poor substrate mixture. Bacterial and fungal diversities of the root and rhizosphere biotopes were relatively resilient following inoculation by microbial suspension; however, bacterial community structure was significantly influenced. Interestingly, four arbuscular mycorrhizal fungi (AMF) were identified as indicator species, including Glomus sp., Claroideoglomus etunicatum, Funneliformis mosseae and an unidentified AMF taxon. We also observed that an ericoid mycorrhizal taxon Sebacina sp. and three Trichoderma spp. were among indicator species. Non-pathogenic Planctobacteria members highly dominated the bacterial community as core and hub taxa for over 80% of all bacterial datasets in root and rhizosphere biotopes. Overall, our study documented that inoculation with a microbial suspension and phytate amendment improved soybean plant growth.

Potential impacts of soil microbiota manipulation on secondary metabolites production in cannabis.

BACKGROUND: Cannabis growing practices and particularly indoor cultivation conditions have a great influence on the production of cannabinoids. Plant-associated microbes may affect nutrient acquisition by the plant. However, beneficial microbes influencing cannabinoid biosynthesis remain largely unexplored and unexploited in cannabis production. OBJECTIVE: To summarize study outcomes on bacterial and fungal communities associated with cannabis using high-throughput sequencing technologies and to uncover microbial interactions, species diversity, and microbial network connections that potentially influence secondary metabolite production in cannabis. MATERIALS AND METHOD: A mini review was conducted including recent publications on cannabis and their associated microbiota and secondary metabolite production. RESULTS: In this review, we provide an overview of the potential role of the soil microbiome in production of cannabinoids, and discussed that manipulation of cannabis-associated microbiome obtained through soil amendment interventions of diversified microbial communities sourced from natural forest soil could potentially help producers of cannabis to improve yields of cannabinoids and enhance the balance of cannabidiol (CBD) and tetrahydrocannabinol (THC) proportions. CONCLUSION: Cannabis is one of the oldest cultivated crops in history, grown for food, fiber, and drugs for thousands of years. Extension of genetic variation in cannabis has developed into wide-ranging varieties with various complementary phenotypes and secondary metabolites. For medical or pharmaceutical purposes, the ratio of CBD to THC is key. Therefore, studying soil microbiota associated with cannabis and its potential impact on secondary metabolites production could be useful when selecting microorganisms as bioinoculant agents for enhanced organic cannabinoid production.

The Aging of Adipocytes Increases Expression of Pro-Inflammatory Cytokines Chronologically.

Adipose tissue is a significant producer of pro-inflammatory cytokines in obese and old individuals. However, there is no direct evidence of whether and how aged adipocytes enhance the production of pro-inflammatory markers. We aimed to investigate whether the aging adipocytes increase pro-inflammatory markers. Swiss mouse embryonic-tissue-derived 3T3-L1 cells were differentiated into adipocytes and maintained for 60 days in the conditioned medium or 35 days in the unconditioned medium. Additionally, 20-month-old male C57BL/6 mice were fed a standard chow diet for 37 weeks until they were extremely aged, when ~75% of mice died because of aging. Accumulated lipids, pro-inflammatory markers, and nuclear factor kappa B (NF-κB) pathway markers from differentiated adipocytes were analyzed. Pro-inflammatory markers and NF-κB pathway markers of epididymal white adipose tissues (EWATs) and adipocytes from EWATs were also analyzed. We found that the aging adipocytes chronologically accumulated lipids and increased pro-inflammatory markers interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α); at the same time, NF-κB p50 markers were also increased while IκBα protein was decreased significantly in conditioned medium. Similar results were observed when differentiated adipocytes were maintained in the unconditioned medium and the adipocytes from EWATs of aged mice. We demonstrated that aging augmented chronic inflammation through the NF-κB signaling pathway in adipocytes and adipose tissue.

Adipose tissue and insulin resistance in obese.

Currently, obesity has become a global health issue and is referred to as an epidemic. Dysfunctional obese adipose tissue plays a pivotal role in the development of insulin resistance. However, the mechanism of how dysfunctional obese-adipose tissue develops insulin-resistant circumstances remains poorly understood. Therefore, this review attempts to highlight the potential mechanisms behind obesity-associated insulin resistance. Multiple risk factors are directly or indirectly associated with the increased risk of obesity; among them, environmental factors, genetics, aging, gut microbiota, and diets are prominent. Once an individual becomes obese, adipocytes increase in their size; therefore, adipose tissues become larger and dysfunctional, recruit macrophages, and then these polarize to pro-inflammatory states. Enlarged adipose tissues release excess free fatty acids (FFAs), reactive oxygen species (ROS), and pro-inflammatory cytokines. Excess systemic FFAs and dietary lipids enter inside the cells of non-adipose organs such as the liver, muscle, and pancreas, and are deposited as ectopic fat, generating lipotoxicity. Toxic lipids dysregulate cellular organelles, e.g., mitochondria, endoplasmic reticulum, and lysosomes. Dysregulated organelles release excess ROS and pro-inflammation, resulting in systemic inflammation. Long term low-grade systemic inflammation prevents insulin from its action in the insulin signaling pathway, disrupts glucose homeostasis, and results in systemic dysregulation. Overall, long-term obesity and overnutrition develop into insulin resistance and chronic low-grade systemic inflammation through lipotoxicity, creating the circumstances to develop clinical conditions. This review also shows that the liver is the most sensitive organ undergoing insulin impairment faster than other organs, and thus, hepatic insulin resistance is the primary event that leads to the subsequent development of peripheral tissue insulin resistance.

High HbA1c is not a reason not to fast during Ramadan in Children, adolescents and young adults with Type 1 diabetes - An observational study in Bangladesh.

AIMS: Our aim was to investigate the ability, frequency of acute complications and impact on glycemic control in uncontrolled T1DM who fasted during Ramadan. METHODS: 74 Patients with T1D who insisted on fasting were enrolled 1 month prior to Ramadan and given intensive education by Diabetes team on insulin dose, glucose monitoring and dietary adjustments. Patients were divided into two groups ; group A- HbA1c < 9%(<75 mmol/mol) and group B- HbA1c ≥ 9% (≥75 mmol/mol) and different variables were compared. RESULTS: Most of the patients fasted 58 (78.4%) for more than 15 days. There was no significant difference (p = 0.790), while comparing the breaking the fast in the two groups. Hypoglycaemia was common acute complications among them. There was no significant difference in the frequency of hypoglycaemia between two groups (P = 0.448). There was increased insulin requirement in both groups during Ramadan (p = 0.00001), with an increase in basal insulin in well controlled (from 24 to 34 units). There was significant reduction of Post Ramadan mean HbA1C in both groups [P = 0.0001)]. CONCLUSION: Children, adolescents and young adults with T1D with poor glycaemic control can fast safely during Ramadan with proper education and intensive monitoring.

Young people with type 1 diabetes on insulin pump therapy could fast safely during COVID-19 pandemic Ramadan: A telemonitoring experience in Bangladesh.

Our aim was to report our telemedicine experience with type 1 diabetes patients using insulin pumps who fasted for Ramadan 2020 during the COVID-19 pandemic. The routine diabetes outpatient care in our Changing Diabetes in Children (CDiC) Pediatric Diabetes Center at the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders hospital was closed, as there was a lockdown from 26 March in Bangladesh. The diabetes team in our center started telemedicine care for routine follow up of patients. Nine patients who wished to fast for Ramadan contacted our diabetes team over the phone. The mean age was 19.3 ± 5.0 years, and five (55.6%) were female. Most of the patients fasted >20 days. Hyperglycemia and mild hypoglycemia were common complications during fasting. There was no episode of severe hypoglycemia or diabetic ketoacidosis, and none of the patients required admission. During the COVID-19 crisis in Bangladesh, patients with type 1 diabetes using an insulin pump could fast safely for Ramadan with the support of the telemedicine service by the diabetes team.

The physio-metabolic effects of time-restricting liquid sugar intake to six-hour windows during the mouse active phase: The effects of active phase liquid sugar consumption.

Obesity is a major public health concern and overconsumption of unhealthy fats and sugary beverages are contributing factors. Time-restricted feeding can reduce obesity-associated pathophysiological parameters by limiting the time of food consumption; however, the effects of time-restricted sugary water consumption are unknown. To examine whether liquid calorie restriction impacts metabolic health, we measured metabolic parameters in mice provided liquid sugar at various intervals during the active phase. The control (Con) group received tap water, the adlibitum fructose-glucose (ALFG) group received ad libitumsugar water and the early fructose-glucose (EFG) and late fructose-glucose (LFG) groups received liquid sugar during the first and last six hours of the active period, respectively. Each group was given free access to chow. Zeitgeber time (ZT) notation was used to set all experimental time points to lights on as ZT 0. The ALFG group exhibited elevated body and adipose tissue weights compared to the other groups and increased hepatic steatosis compared to the Con group. The ALFG group consumed more calories than the other groups during ZT 6-11, indicating that this window may be critical in the promotion of weight gain from liquid sugar consumption. The EFG group exhibited higher levels of energy expenditure than the Con and LFG groups during the first half of the active period (ZT 12-17); however, there was no difference among the groups during the second half of the active period (ZT18-23). In contrast, the EFG group exhibited lower respiratory exchange ratio than other groups during the inactive period as well as the second half of the active period, indicating that the EFG group had greater metabolic flexibility and utilized lipids when carbohydrates from liquid sugar were not available. Additionally, the EFG group was more insulin tolerant than the ALFG and Con groups. Our results support the hypothesis that time-restricted liquid calorie restriction aids in reducing the detrimental metabolic effects of sugary drink consumption.

Western diet-induced obesity disrupts the diurnal rhythmicity of hippocampal core clock gene expression in a mouse model.

Western diet (WD) feeding disrupts core clock gene expression in peripheral tissues and contributes to WD-induced metabolic disease. The hippocampus, the mammalian center for memory, is also sensitive to WD feeding, but whether the WD disrupts its core clock is unknown. To this end, male mice were maintained on a WD for 16 weeks and diurnal metabolism, gene expression and memory were assessed. WD-induced obesity disrupted the diurnal rhythms of whole-body metabolism, markers of inflammation and hepatic gene expression, but did not disrupt diurnal expression of hypothalamic Bmal1, Npas2 and Per2. However, all measured core clock genes were disrupted in the hippocampus after WD feeding and the expression pattern of genes implicated in Alzheimer's disease and synaptic function were altered. Finally, WD feeding disrupted hippocampal memory in a task- and time-dependent fashion. Our results implicate WD-induced alterations in the rhythmicity of hippocampal gene expression in the etiology of diet-induced memory deficits.

Restricted feeding for 9h in the active period partially abrogates the detrimental metabolic effects of a Western diet with liquid sugar consumption in mice.

BACKGROUND: Obesity is a major public health concern that can result from diets high in fat and sugar, including sugar sweetened beverages. A proposed treatment for dietary-induced obesity is time-restricted feeding (TRF), which restricts consumption of food to specific times of the 24-hour cycle. Although TRF shows great promise to prevent obesity and the development of chronic disease, the effects of TRF to reverse metabolic changes and the development of NAFLD in animal models of a Western diet with sugary water consumption is not known. OBJECTIVE: The objective of the current study was to evaluate the role of TRF in the treatment of obesity and NAFLD through examination of changes in metabolic and histopathologic parameters. METHODS: To better understand the role of TRF in the treatment of obesity and NAFLD, we investigated the metabolic phenotype and NAFLD parameters in a mouse model of NAFLD in which obesity and liver steatosis are induced by a Western Diet (WD): a high-fat diet of lard, milkfat and Crisco with sugary drinking water. Mice were subjected to a short-term (4-weeks) and long-term (10-weeks) TRF in which food was restricted to 9h at night. RESULTS: Prior to TRF treatment, the WD mice had increased body mass, and exhibited less activity, and higher average daytime energy expenditure (EE) than chow fed mice. Approximately 4- and 10-weeks following TFR treatment, WD-TRF had moderate but not statistically significant weight loss compared to WD-ad libitum (WD-AL) mice. There was a modest but significant reduction in the inguinal adipose tissue weight in both WD-TRF groups compared to the WD-AL groups; however, there was no difference in epididymal and retroperitoneal adipose tissue mass or adipocyte size distribution. In contrast, the diet-induced increase in normalized liver tissue weight, hepatic triglyceride, and NAFLD score was partially abrogated in the 4-week WD-TRF mice, while systemic insulin resistance was partially abrogated and glucose intolerance was completely abrogated in the 10-week WD-TRF mice. Importantly, WD-induced metabolic dysfunction (substrate utilization, energy expenditure, and activity) was partially abrogated by 4- and 10-week TRF. CONCLUSIONS: Our results support the hypothesis that TRF aids in reducing the detrimental metabolic effects of consuming a WD with sugary drinking water but does not ameliorate obesity.