Animal-based Studies Research Articles

Implications of Resveratrol in Obesity and Insulin Resistance: A State-of-the-Art Review.

Background: Resveratrol is a polyphenol chemical that naturally occurs in many plant-based dietary products, most notably, red wine. Discovered in 1939, widespread interest in the potential health benefits of resveratrol emerged in the 1970s in response to epidemiological data on the cardioprotective effects of wine. Objective: To explore the background of resveratrol (including its origins, stability, and metabolism), the metabolic effects of resveratrol and its mechanisms of action, and a potential future role of dietary resveratrol in the lifestyle management of obesity. Data sources: We performed a narrative review, based on relevant articles written in English from a Pubmed search, using the following search terms: “resveratrol”, “obesity”, “Diabetes Mellitus”, and “insulin sensitivity”. Results: Following its ingestion, resveratrol undergoes extensive metabolism. This includes conjugation (with sulfate and glucuronate) within enterocytes, hydrolyzation and reduction within the gut through the action of the microbiota (with the formation of metabolites such as dihydroresveratrol), and enterohepatic circulation via the bile. Ex vivo studies on adipose tissue reveal that resveratrol inhibits adipogenesis and prevents the accumulation of triglycerides through effects on the expression of Peroxisome Proliferator-activated Receptor γ (PPARγ) and sirtuin 1, respectively. Furthermore, resveratrol induces anti-inflammatory effects, supported by data from animal-based studies. Limited data from human-based studies reveal that resveratrol improves insulin sensitivity and fasting glucose levels in patients with Type 2 Diabetes Mellitus and may improve inflammatory status in human obesity. Although numerous mechanisms may underlie the metabolic benefits of resveratrol, evidence supports a role in its interaction with the gut microbiota and modulation of protein targets, including sirtuins and proteins related to nitric oxide, insulin, and nuclear hormone receptors (such as PPARγ). Conclusions: Despite much interest, there remain important unanswered questions regarding its optimal dosage (and how this may differ between and within individuals), and possible benefits within the general population, including the potential for weight-loss and improved metabolic function. Future studies should properly address these important questions before we can advocate the widespread adoption of dietary resveratrol supplementation.

A Cryoprotectant-Gel Composite Designed to Preserve Articular Cartilage during Frozen Osteoarticular Autograft Reconstruction for Malignant Bone Tumors: An Animal-Based Study.

ObjectiveWe designed a highly adhesive cryoprotectant-gel composite (CGC), based on regular liquid-form cryoprotectant base (CB), aiming to protect cartilage tissue during frozen osteoarticular autograft reconstruction for high-grade sarcoma around the joint. This study aimed to evaluate its effectiveness in rat and porcine distal femur models.DesignFresh articular cartilage samples harvested from distal rat and porcine femurs were divided into 4 test groups: untreated control group, liquid nitrogen (LN) freezing group, LN freezing group pretreated with CB (CB group), and LN freezing group pretreated with CGC (CGC group). Microscopic and macroscopic evaluation of cartilage condition, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, and apoptotic protein analysis of chondrocytes were performed to confirm our results.ResultsIn the rat model, CGC could prevent articular cartilage from roughness and preserve more proteoglycans when compared with the LN freezing and CB groups. Western blot analysis showed CGC could prevent cartilage from LN-induced apoptosis supported by caspase-3/8 apoptotic signaling cascade. Macroscopically, we observed CGC could reduce both articular clefting and loss of articular luminance after freezing in the porcine model. In both models, CGC could reduce articular chondrocytes from degeneration. Fewer TUNEL-positive apoptotic and more viable chondrocytes in cartilage tissue were observed in the CGC group in our animal models.ConclusionOur study proved that CGC could effectively prevent cartilage surface and chondrocytes from cryoinjury after LN freezing. Freezing articular cartilage surrounded with high concentration of CGC can be a better alternative to preserve articular cartilage during limb salvage surgery for malignant bone tumor.

Dabigatran and Wet AMD, Results From Retinal Pigment Epithelial Cell Monolayers, the Mouse Model of Choroidal Neovascularization, and Patients From the Medicare Data Base.

BackgroundAge-related macular degeneration (AMD), the leading cause of irreversible blindness in elderly Caucasian populations, includes destruction of the blood-retina barrier (BRB) generated by the retinal pigment epithelium-Bruch’s membrane complex (RPE/BrM), and complement activation. Thrombin is likely to get access to those structures upon BRB integrity loss. Here we investigate the potential role of thrombin in AMD by analyzing effects of the thrombin inhibitor dabigatran.Material and MethodsMarketScan data for patients aged ≥65 years on Medicare was used to identify association between AMD and dabigatran use. ARPE-19 cells grown as mature monolayers were analyzed for thrombin effects on barrier function (transepithelial resistance; TER) and downstream signaling (complement activation, expression of connective tissue growth factor (CTGF), and secretion of vascular endothelial growth factor (VEGF)). Laser-induced choroidal neovascularization (CNV) in mouse is used to test the identified downstream signaling.ResultsRisk of new wet AMD diagnosis was reduced in dabigatran users. In RPE monolayers, thrombin reduced TER, generated unique complement C3 and C5 cleavage products, led to C3d/MAC deposition on cell surfaces, and increased CTGF expression via PAR1-receptor activation and VEGF secretion. CNV lesion repair was accelerated by dabigatran, and molecular readouts suggest that downstream effects of thrombin include CTGF and VEGF, but not the complement system.ConclusionsThis study provides evidence of association between dabigatran use and reduced exudative AMD diagnosis. Based on the cell- and animal-based studies, we suggest that thrombin modulates wound healing and CTGF and VEGF expression, making dabigatran a potential novel treatment option in AMD.

3-(((1S,3S)-3-((R)-Hydroxy(4-(trifluoromethyl)phenyl)methyl)-4-oxocyclohexyl)methyl)pentane-2,4-dione: Design and Synthesis of New Stereopure Multi-Target Antidiabetic Agent.

The chiral drug candidates have more effective binding affinities for their specific protein or receptor site for the onset of pharmacological action. Achieving all carbon stereopure compounds is not trivial in chemical synthesis. However, with the development of asymmetric organocatalysis, the synthesis of certain vital chiral drug candidates is now possible. In this research, we have synthesized 3-(((1S,3S)-3-((R)-hydroxy(4-(trifluoromethyl)phenyl)methyl)-4-oxocyclohexyl)methyl)pentane-2,4-dione (S,S,R-5) and have evaluated it potential as multi-target antidiabetic agent. The stereopure compound S,S,R-5 was synthesized with a 99:1 enantiomeric ratio. The synthesized compound gave encouraging results against all in vitro antidiabetic targets, exhibiting IC50 values of 6.28, 4.58, 0.91, and 2.36 in α-glucosidase, α-amylase, PTP1B, and DPPH targets, respectively. The molecular docking shows the binding of the compound in homology models of the respective enzymes. In conclusion, we have synthesized a new chiral molecule (S,S,R-5). The compound proved to be a potential inhibitor of the tested antidiabetic targets. With the observed results and molecular docking, it is evident that S,S,R-5 is a potential multitarget antidiabetic agent. Our study laid the baseline for the animal-based studies of this compound in antidiabetic confirmation.

MicroRNAs in cardiovascular diseases.

Cardiovascular diseases (CVDs) are the leading causes of death and disability worldwide, despite the wide diversity of molecular targets identified and the development of therapeutic methods. MicroRNAs (miRNAs) are a class of small (about 22 nucleotides) non-coding RNAs (ncRNAs) that negatively regulate gene expression at the post-transcriptional level in the cytoplasm and play complicated roles in different CVDs. While miRNA overexpression in one type of cell protects against heart disease, it promotes cardiac dysfunction in another type of cardiac cell. Moreover, recent studies have shown that, apart from cytosolic miRNAs, subcellular miRNAs such asmitochondria- and nucleus-localized miRNAs are dysregulated in CVDs. However, the functional properties of cellular- and subcellular-localized miRNAs have not been well characterized. In this review article, by carefully revisiting animal-based miRNA studies in CVDs, we will address the regulation and functional properties of miRNAs in various CVDs. Specifically, the cell-cell crosstalk and subcellular perspective of miRNAs are highlighted. We will provide the background for attractive molecular targets that might be useful in preventing the progression of CVDs and heart failure (HF) as well as insights for future studies.

Thinned Nectarines, an Agro-Food Waste with Antidiabetic Potential: HPLC-HESI-MS/MS Phenolic Characterization and In Vitro Evaluation of Their Beneficial Activities.

Due to the side effects of synthetic drugs, the interest in the beneficial role of natural products in the management of diabetic conditions is growing over time. In the context of agro-food waste products, a screening of different fruit thinning by-products identified thinned nectarines (TN) as the richest matrices of abscisic acid (ABA), a phytohormone with well-documented hypoglycemic potential. These waste-food matrices may represent not only precious sources of ABA but also other bioactive molecules with potential health benefits, such as polyphenols. Therefore, we aimed to perform a qualitative and quantitative characterization of a polyphenolic profile of a TN-based nutraceutical formulation through HPLC-HESI-MS/MS and HPLC-DAD-FLD analyses. Additionally, the in vitro antioxidant and antidiabetic potential of TN was investigated. HPLC analyses allowed us to identify forty-eight polyphenolic compounds, nineteen of which were quantified. Moreover, the results obtained through different in vitro assays showed the antioxidant and antidiabetic potential exerted by the tested nutraceutical formulation. In conclusion, the concomitant presence of different bioactive compounds in TN-based nutraceutical formulation, such as ABA and polyphenols, would reasonably support TN as an innovative nutraceutical formulation useful for the management of glucose homeostasis. Further in-depth animal-based studies and clinical trials are needed to deepen these aspects.

BMAL1 Regulates the Daily Timing of Colitis.

Many physiological functions exhibit circadian rhythms: oscillations in biological processes that occur in a 24-hour period. These daily rhythms are maintained through a highly conserved molecular pacemaker known as the circadian clock. Circadian disruption has been proposed to cause increased risk of Inflammatory Bowel Disease (IBD) but the underlying mechanisms remain unclear. Patients with IBD experience chronic inflammation and impaired regeneration of intestinal epithelial cells. Previous animal-based studies have revealed that colitis models of IBD are more severe in mice without a circadian clock but the timing of colitis, and whether its inflammatory and regenerative processes have daily rhythms, remains poorly characterized. We tested circadian disruption using Bmal1-/- mutant mice that have a non-functional circadian clock and thus no circadian rhythms. Dextran Sulfate Sodium (DSS) was used to induce colitis. The disease activity of colitis was found to exhibit time-dependent variation in Bmal1+/+ control mice but is constant and elevated in Bmal1-/- mutants, who exhibit poor recovery. Histological analyses indicate worsened colitis severity in Bmal1-/- mutant colon, and colon infiltration of immune system cells shows a daily rhythm that is lost in the Bmal1-/- mutant. Similarly, epithelial proliferation in the colon has a daily rhythm in Bmal1+/+ controls but not in Bmal1-/- mutants. Our results support a critical role of a functional circadian clock in the colon which drives 24-hour rhythms in inflammation and healing, and whose disruption impairs colitis recovery. This indicates that weakening circadian rhythms not only worsens colitis, but delays healing and should be taken into account in the management of IBD. Recognition of this is important in the management of IBD patients required to do shift work.

Keio Uterus Transplantation Research: From Basic Research toward Future Clinical Application.

Uterus transplantation (UTx) is now a potential option to allow women with uterine factor infertility to give birth. However, UTx is still at an experimental stage, and basic animal studies, including in non-human primates, are needed for the accumulation of data prior to clinical application. Considering that UTx may provide new hope to Japanese women, we launched UTx research in 2009 and have since accumulated a large archive of results in the UTx research field. Furthermore, we have carried out various activities aimed at the implementation of clinical applications of UTx in Japan while clarifying the ethical and social issues involved. Currently, the clinical application of UTx in Japan is just around the corner, and it is expected that UTx research will develop further in the future. Herein, we summarize our basic experiences using non-human primates and our activities with the goal of future clinical applications.

An integrative pan-cancer analysis reveals the oncogenic role of mutS homolog 6 (MSH6) in human tumors.

There are three most important mismatch repair genes in the mismatch repair system, MSH6 is one of them and it plays an essential role in DNA mismatch repair. Several emerging cell- or animal-based studies have verified that MSH6 mutations are closely linked to the occurrence, progression or metastasis of cancer, but there is still no practicable pan-cancer analysis. On account of the available datasets of the cancer genome atlas (TCGA) and Gene expression omnibus (GEO), a comprehensive analysis of the potential carcinogenic effects of the MSH6 gene was conducted in 33 human cancers. MSH6 was highly expressed in most cancers, and the high expression of MSH6 was associated with poor overall survival prognosis of patients with multiple cancers, such as adrenocortical carcinoma. MSH6 mutations occurred in most cancers and were closely related to the prognosis of cancer patients. Increased phosphorylation levels of S227 and S830 were noted in several tumors, including breast cancer and colon cancer. MSH6 expression was also observed to be correlated with cancer-associated fibroblasts and CD8+ T-cells infiltration levels in various cancer types, e. g. pancreatic adenocarcinoma or testicular germ cell tumors. Furthermore, pathway enrichment analysis demonstrated that the main biological activities of MSH6 were related to ATPase activity, mismatch repair, and DNA metabolism-related functions. Altogether, our pan-cancer research has suggested that the MSH6 expression level was closely related to the carcinogenesis and prognosis of certain tumors, which helps to know the effect of MSH6 in tumorigenesis from the point of view of clinical tumor samples.

Alantolactone: A Natural Plant Extract as a Potential Therapeutic Agent for Cancer.

Alantolactone (ALT) is a natural compound extracted from Chinese traditional medicine Inula helenium L. with therapeutic potential in the treatment of various diseases. Recently, in vitro and in vivo studies have indicated cytotoxic effects of ALT on various cancers, including liver cancer, colorectal cancer, breast cancer, etc. The inhibitory effects of ALT depend on several cancer-associated signaling pathways and abnormal regulatory factors in cancer cells. Moreover, emerging studies have reported several promising strategies to enhance the oral bioavailability of ALT, such as combining ALT with other herbs and using ALT-entrapped nanostructured carriers. In this review, studies on the anti-tumor roles of ALT are mainly summarized, and the underlying molecular mechanisms of ALT exerting anticancer effects on cells investigated in animal-based studies are also discussed.

Multi-omic studies on the toxicity variations in effluents from different units of reclaimed water treatment

The conventional reclaimed water technologies could not effectively remove the micropollutants. Although the health risks of these residual micropollutants have been evaluated by model calculation, few animal-based studies have been performed, which is essential for risk verification. Here, we used transcriptomic, metabolomic, and other biochemical techniques to reveal the toxicity variations of effluents from oxidation ditch (OD), coagulation tank (CT), biological aerated filter (BAF), and ultraviolet disinfection pool (UV) in a reclaimed water plant located in Nanjing, China. No evident toxicity reduction trend was observed along the treatment units. Compared with control and other three treatment unit effluents, long-term exposure to reclaimed water (UV effluent) aggravated oxidative stress in mice and induced abnormal lipid metabolism and immune response. Moreover, striking correlations were identified between multi-omic biomarkers (4 differentially expressed genes and 8 significant changes metabolites) and residual micropollutants (40 semi-volatile organic compounds and 6N-nitrosamines). Our results strongly highlight that the health risks of reclaimed water are mainly induced by the residual micropollutants, and more advanced treatments and stringent discharge standards are needed to ensure the safety of reclaimed water.

The Potential Therapeutic Effects of Agmatine, Methylprednisolone, and Rapamycin on Experimental Spinal Cord Injury.

Objective In spinal cord injury (SCI), the primary mechanical damage leads to a neuroinflammatory response and the secondary neuronal injury occurs in response to the release of reactive oxygen species (ROS). In addition to the suppression of inflammation, autophagy plays a significant role in the survival of neurons during secondary SCI. The present study aimed to examine the anti-inflammatory and autophagic effects of agmatine and rapamycin in SCI and to compare the results with methylprednisolone (MP) used in the clinic. Materials and Methods In this animal-based experimental study, thirty adult male Sprague-Dawley rats were randomly divided into five groups as sham-control, injury, injury+MP, injury+rapamycin, injury+agmatine groups. SCI was induced by compressing the T7-8-9 segments of the spinal cord, using an aneurysm clip for one minute, and then rats were treated daily for 7 days. Seven days post-treatment, damaged spinal cord tissues of sacrificed rats were collected for microscopic and biochemical examinations using histopathologic and transmission electron microscope (TEM) scores. Malondialdehyde (MDA) and glutathione peroxidase (GPx) levels were spectrophotometrically measured. Results The results of this study showed that the damaged area was smaller in the rapamycin group when compared to the MP group. Many autophagic vacuoles and macrophages were observed in the rapamycin group. Degeneration of axon, myelin, and wide edema was observed in SCI by electron microscopic observations. Fragmented myelin lamellae and contracted axons were also noted. While MDA and GPx levels were increased in the injury group, MDA levels were significantly decreased in the agmatine and MP groups, and GPx levels were decreased in the rapamycin group. ConclusionThe results of our study confirmed that rapamycin and agmatine can be an effective treatment for secondary injury of SCI.

Creation of an inventory of quality markers used to evaluate pharmacokinetic literature: A systematic review.

Robust critical appraisal tools for clinical pharmacokinetic studies are limited. Before development of such a tool is possible, quality markers (items deemed important for credibility of study results) must be identified. We aim to create an inventory of quality markers intended for the appraisal of clinical pharmacokinetic studies and to categorize identified markers into associated domains of study quality. Medline via ProQuest central (1946-Sep 2020, EMBASE (1974-Sep 2020), Cochrane database of systematic reviews, Google and Google Scholar were searched using the following search categories: pharmacokinetics, reporting guidelines and quality markers. Reference lists of the identified articles were searched manually. Any article (review, study or guideline) reporting quality markers related to the appraisal of pharmacokinetic literature was eligible for inclusion. Articles were further screened and limited to those reported in English on human subjects only. Cell-based and animal-based pharmacokinetic studies were excluded. Extracted data from included articles included identified or perceived markers of quality and baseline article data. Identified quality markers were then categorized according to manuscript reporting domains (abstract, introduction/background, methodology, results, discussion and conclusion). Of 789 studies identified, 17 articles were included for extraction of quality markers. A total of 35 quality markers were identified across eight categories. The most frequently reported quality markers were related to method (13/35) and result sections (6/35). Quality markers encompassed all aspects of study design and reporting and were both similar and different to established reporting checklists for clinical pharmacokinetic studies. The inventory of quality markers is now suitable to undergo further testing for inclusion in a tool designed for the appraisal of clinical pharmacokinetic studies.

The Association between Vitamin D and Gut Microbiota: A Systematic Review of Human Studies.

Recent evidence has shown a number of extra-skeletal functions of Vitamin D (VD), primarily involving the immune system. One of these functions is mediated by the modulation of gut microbiota, whose alterations are linked to many diseases. Our purpose is to contribute to the understanding of existing evidence on the association between VD and gastrointestinal microbiota alterations. A systematic review of studies with human subjects has been conducted up to January 2021. We included publications reporting the association between gut microbiota and VD, including VD supplementation, dietary VD intake and/or level of 25(OH)D. We identified 25 studies: 14 were interventional and 11, observational. VD supplementation was found to be associated with a significant change in microbiome composition, in particular of Firmicutes, Actinobacteria and Bacteroidetes phyla. Furthermore, Firmicutes were found to be correlated with serum VD. Concerning alpha and beta diversity, a high nutritional intake of VD seems to induce a shift in bacterial composition and/or affects the species’ richness. Veillonellaceae and Oscillospiraceae families, in the Firmicutes phylum, more frequently decreased with both increasing levels of 25(OH)D and vitamin D supplementation. We found evidence of an association, even though the studies are substantially heterogeneous and have some limitations, resulting sometimes in conflicting results. To further understand the role of VD on the modulation of the gastrointestinal microbiota, future research should be geared toward well-designed animal-based studies or larger randomized controlled trials (RCTs).

Time-restricted Eating for the Prevention and Management of Metabolic Diseases.

Time-restricted feeding (TRF, animal-based studies) and time-restricted eating (TRE, humans) are an emerging behavioral intervention approach based on the understanding of the role of circadian rhythms in physiology and metabolism. In this approach, all calorie intake is restricted within a consistent interval of less than 12 hours without overtly attempting to reduce calories. This article will summarize the origin of TRF/TRE starting with concept of circadian rhythms and the role of chronic circadian rhythm disruption in increasing the risk for chronic metabolic diseases. Circadian rhythms are usually perceived as the sleep-wake cycle and dependent rhythms arising from the central nervous system. However, the recent discovery of circadian rhythms in peripheral organs and the plasticity of these rhythms in response to changes in nutrition availability raised the possibility that adopting a consistent daily short window of feeding can sustain robust circadian rhythm. Preclinical animal studies have demonstrated proof of concept and identified potential mechanisms driving TRF-related benefits. Pilot human intervention studies have reported promising results in reducing the risk for obesity, diabetes, and cardiovascular diseases. Epidemiological studies have indicated that maintaining a consistent long overnight fast, which is similar to TRE, can significantly reduce risks for chronic diseases. Despite these early successes, more clinical and mechanistic studies are needed to implement TRE alone or as adjuvant lifestyle intervention for the prevention and management of chronic metabolic diseases.

Examining the Developmental Trajectory of an in Vitro Model of Mouse Primordial Germ Cells following Exposure to Environmentally Relevant Bisphenol A Levels.

Background:Animal-based studies indicate that bisphenol A (BPA) exposure is detrimental to reproductive health, but its impact on the earliest stages of germ cell development remains poorly defined.Objectives:Using a murine in vitro model of early germ cell specification and differentiation, we sought to assess whether exposure to low levels of BPA prior to formation of primordial germ cells (PGCs) alters their differentiation trajectory and unique molecular program.Methods:We used an established method of in vitro differentiation of mouse embryonic stem cells (ESCs) into epiblast-like cells (EpiLCs) followed by PGC-like cells (PGCLCs), which together recapitulate defined stages of early germ cell development. Cellular consequences were determined using hemocytometer-based cell counting, fixation, and intracellular staining, followed by flow cytometry/fluorescence-activated cell sorting (FACS) of cells exposed to increasing concentrations (range: ) of BPA. To interrogate and characterize gene expression differences resulting from BPA exposure, we also generated RNA-seq libraries from RNA extracted from FACS-purified PGCLCs and performed transcriptome analysis using bioinformatics-based approaches.Results:Exposure of EpiLCs to BPA resulted in higher numbers of cells that were associated with a higher proportion of cells in S-phase as well as a lower proportion undergoing apoptosis; this difference occurred in a concentration-dependent manner. Exposure also resulted in a greater fraction of EpiLCs showing signs of DNA damage. Remarkably, EpiLC exposure did not negatively affect PGC specification and resulted in a concentration-dependent effect on PGCLC proliferation in XX but not XY cells. PGCLC transcriptome analysis revealed an aberrant program with significant deregulation of X-linked genes and retrotransposon expression. Differential gene expression analysis also revealed the deregulation of genes associated with lipid metabolism as well as deregulated expression of genes associated with later stages of gametogenesis.Conclusions:To the best of our knowledge our findings represent the first characterization of the consequences of early BPA exposure on a model of mammalian PGC development, highlighting altered cell behavior, altered underlying pathways, and altered molecular processes. https://doi.org/10.1289/EHP8196

Elucidating the interaction between maternal physical activity and circulating myokines throughout gestation: A scoping review.

Physical activity (PA) during pregnancy provides both maternal and fetal health benefits. It has been theorized that myokines, peptides secreted by contracting skeletal muscle, may play an important mechanistic role in facilitating the health benefits obtained from prenatal exercise. The objective of this review was to synthesize the current literature on the relationship between maternal PA and myokine response. A search strategy was developed using the terms pregnancy, PA, IL-6, IL-10, IL-13, and TNF-α. A systematic search was completed in July 2020, in Medline, SPORTDiscus, EMBASE, CENTRAL, and in November 2020 for unpublished dissertations (grey literature; Proquest). Both human- and animal-based studies of any design were included, while commentaries and editorial articles were excluded. Data were extracted by two independent reviewers and summarized narratively. Data were thematically summarized based on the myokine and whether findings were from human or animal studies. Ten studies were included in this review. Findings from studies that examined IL-6, IL-10, and TNF-α suggest a trimester-specific interaction between PA and myokine levels; no studies evaluated IL-13. Future research should investigate the PA-myokine relationship throughout all stages of gestation.

Effect of fish oil on multiplication of Halicephalobus (Nematoda: Rhabditida)

Laboratory mass rearing of nematode is a low-cost method to provide a good source for laboratory analysis. Laboratory mass rearing of free-living nematode provide a significant source for genetic, phylogenetic and physiological analysis of the nematode and animal-based study. This investigation was conducted during 2017 at North University of South Africa to find out the best condition for mass rearing of free-living nematode. The Media, including Water Agar 1.5%, WA 1.5% + fish oil, WA 1.5% + K2HPO4, and Nutrient Agar + fish oil was used for their evaluation for multiplication of Halicephalobus in the laboratory condition. One mL fish oil extracted from milk was added to the media WA 1.5% + fish oil and NA + fish oil and incubated at room temperature. The nematodes number four, seven, and fourteen-day after inoculation in WA 1.5% amended with fish oil, and the other media were counted. These results showed that the multiplication of nematodes in WA 1.5% + fish oil (612.3 ± 36; after 7 days) was much more than other media for multiplication of Halicephalobus. Therefore, fish oil is a good option to add to the media to multiply the free-living nematodes in laboratory conditions.

Stem cell therapy for degenerative disc disease: A review

Degenerative Disc Disease (DDD) is a prevalent musculoskeletal disorder associated with lower back pain that typically occurs with age but can also be precipitated by other factors. At present, the available treatments such as physical therapy, analgesics, anti-inflammatory drugs, and surgical interventions are aimed at addressing the symptoms of the disease but not the degeneration process. Among the various biological disc repair therapies, cell therapy has gained interest as it offers a disc regenerative potential while being minimally invasive. Stem cells have the unique property of differentiating into chondrocytes (specialized cells found in cartilage) that resemble Nucleus Pulposus (NP) cells of the disc. Therefore, stem cells can be used to replace the lost NP cells in the degenerated disc. This reduces inflammation and helps in the regeneration of the degenerated disc. In vitro studies, several animal-based studies, and a few human pilot studies have demonstrated safety and efficacy in the treatment of DDD with different types of Mesenchymal Stem Cells (MSCs), Induced Pluripotent Stem Cells (IPSCs), and Intervertebral Disc Stem Cells (IVDSCs). This review aims to address the current status, recent advancements, and different types of stem cells in degenerated disc therapy.

Novel Nutritional and Dietary Approaches to Weight Loss for the Prevention of Cardiovascular Disease: Ketogenic Diet, Intermittent Fasting, and Bariatric Surgery.

Cardiovascular disease (CVD) is highly associated with obesity and cardiometabolic dysfunction. This review will focus on three novel therapies that have been identified for potential treatment of obesity and its associated CVD risk factors. Intermittent fasting (IF) studies in animal models have shown improvements in cardiometabolic factors, including improved glucose metabolism, reduced inflammation, and reduced blood pressure. However, there is still a lack of prospective human trials to support results from animal-based studies and observational data. Studies of ketogenic diets in humans have produced mixed effects in CVD risk factors. It has been shown that the ketogenic diet (KD) increases low-density lipoprotein cholesterol (LDL-C) but decreases triglycerides. Additionally, implementation of KD in rodent studies have demonstrated increased insulin resistance and glucose intolerance. Bariatric surgery is a useful tool to help patients with obesity lose significant amounts of weight while alleviating CVD risk factors such as hypertension, LDL-C levels, triglyceride levels, and diabetes. The type of procedure influences degree of improvement in weight and CVD risk factors, yet complications remain possible. IF and bariatric surgery offer potential for weight loss and treatment of CVD risk factors. Negative cardiovascular effects of KD have been noted and should be considered before recommending this diet to patients, particularly those with established cardiovascular disease.