The United Nations Organization (UNO) has proposed achieving specific Sustainable Development Goals (SDGs), including poverty, hunger, health, education, equality, climate change, and the need for sustainable development, while protecting the planet Earth from environmental degradation. The expert group of the International College of Nutrition aims to emphasize the merits of sustainable diets and traditional plant based foods for the primordial prevention of cardio-metabolic Diseases (CMDs) and other chronic diseases in this review, to achieve these goals. A narrative review was conducted to identify articles related to cardiovascular diseases (CVDs), obesity, diabetes, and cancer, using databases from the World Health Organization (WHO), Google Scholar, MEDLINE (PubMed), Web of Science, and EBSCO, along with additional secondary sources and a search of grey literature. Opinions of experts were also sought, and views of all authors were obtained as outlined in this document. It seems that education, in particular health education and motivation, apart from cultural factors, are crucial for achieving total health, and the SDGs of the UNO. The prevalence of unhealthy behaviours and risk factors for most of the CMDs and other chronic diseases is rapidly increasing in low- and middle-income countries, due to the ongoing economic development, leading to rapid changes in diet and lifestyle. There is some decline in cardiovascular disease (CVD) mortality in high-income countries due to education and learning of preventive strategies, resulting in a reduction in mortality due to these diseases. However, CMDs and cancer remain the significant causes of morbidity and mortality. During and after World War II, food scarcity persisted from 1940 to 1965 in most countries, accompanied by a low risk of cardiovascular disease (CVD) and diabetes. The rapid increase in industrialization and urbanization has been linked to environmental degradation on planet Earth, a decline in fertile, healthy soil, and sustainable, functional farming practices, resulting in a decrease in the production of nutritious foods. These alterations in food availability are associated with an increased production of unhealthy, energy rich foods and Western-type dietary patterns, which in turn increased the risk of non-communicable diseases (NCDs). The health of the planet and its people is at risk. There is a deterioration in the global standard of natural systems that support life on Earth, which is exacerbating energy, food, and water insecurity, and increasing the risk of disease, disaster, displacement, and conflict. Recent advice about the safe corridor on the planet can enhance research on planetary boundaries and Earth-system aspects of the SDGs. It appears that poverty, lack of education, and inadequate health education and motivation, possibly due to ineffective policies by national and local governments, are significant determinants of the increased risk of these diseases. In urban areas of lower and middle-income countries, as well as in immigrant populations in high-income countries, CMDs and other chronic diseases are significantly higher than they are in some of the high-income populations. Improvements in soil and the promotion of functional farming, along with an emphasis on the food industry, are urgently needed to support plant-based, low-animal food traditional food diets. Traditional foods are feasible and affordable in every country. The use of high-protein substitutes for animal-derived foods, such as soybean products such as tofu and tempe, millets, beans, lentils, peas (400 g/day), green vegetables, fruits, and nuts (400 g/day), as well as vegetable oils, low-fat dairy products, and culinary spices, with low meat (sea-foods) may be beneficial in promoting health and preventing NCDs. Health education and promotion of healthier lifestyles and behaviours during the preconception period, in utero life, and the postnatal development and infancy stages may lead to healthy eating patterns, contributing to primordial prevention of NCDs. A wild-type omega-6/3 diet rich in flavonoids, folate, and other nutrients, along with other interventions may mitigate epigenetic risk variations at the individual level across all subgroups, from the preconception period to the elderly stages. These findings may necessitate revisions to the existing guidelines proposed for sustainable functional farming and sustainable plant based diets. Eating 400 g/day of vegetable, fruits, and nuts and another 400 g/day of whole grains, with spices (20-50 g/day) and meat as condiment (50 g/day), along with 30-50 g/day of vegetable oils, can prevent CMDs and other chronic diseases, and promote health to serve the SDGs of the UNO. Cohort studies and randomized trial in each country may be necessary to confirm the role of our advice in the prevention of diseases.

β-Caryophyllene (BCP), a selective agonist of cannabinoid receptor type 2 (CB2), has garnered attention as a promising nutraceutical agent for modulating organ damage. The current study aimed at evaluating the pharmacological role of BCP in Thioacetamide (TAA)-induced liver fibrosis, with particular attention to the involvement of CB2-mediated signaling. Following the induction of fibrosis by TAA, rats were treated with BCP for 6 weeks. In a separate group, AM630, a selective CB2 receptor antagonist, was co-administered with BCP in order to validate CB2-dependent actions. TAA administration triggered significant hepatocellular injury. In addition, TAA activated necroptotic cellular death, shown in the upregulated RIPK1/RIPK3/p-MLKL expression. Growth factors' signaling was disrupted and liver regeneration was impaired. On the contrary, BCP treatment ameliorated oxidative stress, mitigated inflammation, and decreased hepatic stellate cells' activation. This was accompanied by reduced collagen deposition and attenuated fibrosis. BCP markedly abrogated necroptosis and decreased the stimulation of fibrogenic and angiogenic signaling. Additionally, BCP potentiated hepatocytes' survival and restored hepatic regenerative capacity. AM630 co-treatment abolished BCP's protective effects, confirming the CB2 receptors-dependent effects. Given findings highlight BCP as a potential therapeutic agent for liver fibrosis and delineate endocannabinoid system's role in modulating organ fibrosis.

Liver fibrosis is associated with increased rates of morbidity and mortality. At present, there are no specific treatments that can directly reverse hepatic fibrosis. The endocannabinoid system has been found to play a significant role in regulating the development and progression of liver diseases, in addition to having protective effects. In this study, we investigate the protective potential of β-Caryophyllene (BCP) against Thioacetamide (TAA)-induced liver fibrosis. Wistar rats were injected with TAA (200 mg/kg) three times per week for 8 weeks to induce liver fibrosis. They also received oral BCP before the TAA injections. AM630 (1 mg/kg) was administered to confirm the CB2 receptor-dependent effect of BCP. The BCP treatment (50 mg/kg) protected against cell injury and potentiated antioxidant defense by replenishing hepatic GSH, improving catalase activity, and inhibiting the formation of MDA. The co-administration of BCP mitigated the TAA-induced inflammatory response by decreasing the release of proinflammatory cytokines. Histological examination showed preserved cellular integrity, decreased collagen deposits with other extracellular matrix proteins, and low levels of myofibroblast activation. In addition, the BCP-treated rats demonstrated upregulated sirtuin 1 (SIRT1) expression, which had a direct inhibitory effect on hypoxia inducible factor (HIF-1α). AM630 pre-treatment inhibited all the aforementioned protective mechanisms of BCP. Based on our findings, BCP exerts protective effects in liver fibrosis, which can be attributed to its agonist action on CB2 receptors. This study provides preclinical evidence of the potential preventative benefits of BCP in liver fibrosis.

Type 2 diabetes mellitus (T2DM) is known to increase the risk of fragility fractures; however, the underlying mechanism is still elusive. Reduced miR-155 and elevated RHOA are known to drive bone resorption, but their role in T2DM remains unclear. This study investigates bone remodeling imbalances in T2DM through miR-155 and RHOA expression profiling. Three-month-old female Wistar rats were fed a high-calorie diet for 3 weeks, followed by intraperitoneal injections of two lower doses of streptozotocin at weekly intervals to induce T2DM. Bone analysis from diabetic rats tested using qRT-PCR showed significantly reduced miR-155 levels and elevated RHOA. Histological analysis showed a 12.65% increase in Tb.Sp, 10.07% decrease in Tb.Th, and significant increase (p < 0.05) in apoptotic osteocytes. The bone turnover marker CTx-1 level was increased by 20.84%, and RANKL levels were significantly increased in T2DM. IL-1β and TNF-α were increased in T2DM. Bone resorption is more likely to occur in T2DM as both IL-1β and TNF-α work synergistically to promote osteoclastogenesis. MiR-155 could be an important modulator of bone remodeling in T2DM and a potential therapeutic target for diabetic osteopathy.

Inflammatory bowel diseases (IBDs), such as ulcerative colitis, and Crohn’s disease are chronic idiopathic inflammatory diseases of the gastrointestinal system involving interaction between genetic and environmental factors mediating the occurrence of oxidative stress and inflammation. There is no permanent cure for IBD except long-term treatment or surgery (resection of the intestine), and the available agents in the long term appear unsatisfactory and elicit numerous adverse effects. To keep the disease in remission, prevent relapses and minimize adverse effects of currently used medicines, novel dietary compounds of natural origin convincingly appear to be one of the important therapeutic strategies for the pharmacological targeting of oxidative stress and inflammation. Therefore, it is imperative to investigate plant-derived dietary agents to overcome the debilitating conditions of IBD. In the present study, the effect of α-Bisabolol (BSB), a dietary bioactive monoterpene commonly found in many edible plants as well as important components of traditional medicines, was investigated in acetic acid (AA)-induced colitis model in rats. BSB was orally administered to Wistar male rats at a dose of 50 mg/kg/day either for 3 days before or 30 min after induction of IBD for 7 days through intrarectal administration of AA. The changes in body weight, macroscopic and microscopic analysis of the colon and calprotectin levels in the colon of rats from different experimental groups were observed on day 0, 2, 4, and 7. The levels of myeloperoxidase (MPO), a marker of neutrophil activation, reduced glutathione (GSH) and malondialdehyde (MDA), a marker of lipid peroxidation, and the levels of pro-inflammatory cytokines were measured. AA caused a significant reduction in body weight and induced macroscopic and microscopic ulcers, along with a significant decline of endogenous antioxidants (superoxide dismutase (SOD), catalase, and GSH), with a concomitant increase in MDA level and MPO activity. BSB significantly improved the AA-induced reduction in body weight, colonic mucosal histology, inhibited MDA formation, and restored antioxidant levels along with a reduction in MPO activity. AA also induced the release of pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-23 (IL-23) and tumor necrosis factor-α (TNF-α). Furthermore, AA also increased levels of calprotectin, a protein released by neutrophils under inflammatory conditions of the gastrointestinal tract. BSB treatment significantly reduced the release of calprotectin and pro-inflammatory cytokines. The findings of the present study demonstrate that BSB has the potential to improve disease activity and rescue colonic tissues from damage by inhibiting oxidative stress, lipid peroxidation and inflammation. The findings are suggestive of the benefits of BSB in IBD treatment and substantiate its usefulness in colitis management, along with its gastroprotective effects in gastric ulcer.

Background:Peptic ulcer disease (PUD) arises from an imbalance between harmful factors like gastric acid and pepsin, and the protective mechanisms of the gastrointestinal lining, particularly the mucus-bicarbonate barrier. Standard treatments include proton pump inhibitors (e.g., lansoprazole) and histamine H₂-receptor antagonists (e.g., ranitidine), but these can have adverse effects. Withania coagulans, a plant used in Ayurvedic medicine, has traditionally been considered to have anti-ulcer properties. This study investigated the potential of W. coagulans fruit extract to protect against gastric ulcers, possibly via H₂ receptor antagonism. Aim:To evaluate the gastroprotective effects and underlying mechanisms of W. coagulans fruit extract in a rat model of gastric ulcer. Methods:A dose-response study was conducted using rats divided into six groups: naïve, ulcer control, and four groups treated with W. coagulans extract (1, 5, 10, or 20 mg/kg). Acidified ethanol was used to induce ulcers. In another experiment, pylorus-ligated rats were used to assess the extract's effect on gastric acid secretion in response to dimaprit, a histamine analog. For efficacy comparison, rats were pretreated with W. coagulans, lansoprazole, or ranitidine before ulcer induction. Gastric tissues were analyzed for biochemical markers, including cytokines, mucus, prostaglandin E2 (PGE2), and myeloperoxidase activity. Results:The 10 mg/kg dose was most effective in reducing gastric ulceration. The extract reduced gastric acid secretion, like H₂ blockers. It also showed stronger antioxidant activity in gastric tissues compared to lansoprazole and ranitidine. Additionally, it reduced pro-inflammatory cytokines (IL-1β, TNF-α, IL-6), increased anti-inflammatory cytokines (IL-10, TGF-β), enhanced mucus and PGE2 production, and lowered myeloperoxidase activity. Conclusion:Withania coagulans fruit extract at 10 mg/kg significantly protects against acid-induced gastric ulcers. Its effects are comparable to H₂ receptor blockers and include notable antioxidant and anti-inflammatory benefits.

Aims: The global prevalence of waterpipe tobacco smoking is increasing. Although the cardiorespiratory, renal, and reproductive effects of waterpipe smoking (WPS) are well-documented, there is limited knowledge regarding its adverse impact on the liver. Therefore, our study aimed to assess the effects and potential mechanisms of WPS inhalation for one or four weeks on the liver. Main methods: Mice were exposed to WPS for 30 min per day, five days per week, while control mice were exposed to clean air. Key findings: Analysis using light microscopy revealed the infiltration of immune cells (neutrophils and lymphocytes) accompanied by vacuolar hepatic degeneration upon WPS inhalation. At the four-week timepoint, electron microscopy analysis demonstrated an increased number of mitochondria with a concomitant pinchingoff of hepatocyte plasma membranes. WPS exposure led to a significant rise in the activities of liver enzymes alanine aminotransferase and aspartate aminotransferase in the bloodstream. Additionally, WPS inhalation elevated lipid peroxidation and reactive oxygen species levels and disrupted the levels of the antioxidant glutathione in liver tissue homogenates. The concentration of proinflammatory cytokines, including tumor necrosis factor alpha, interleukin (IL)-6, and IL-1 beta, was significantly increased in the WPS-exposed group. Furthermore, WPS inhalation induced DNA damage and a significant increase in the levels of cleaved caspase-3, cytochrome C and hypoxia-inducible factor 1 alpha along with alterations in the activity of mitochondrial complexes I, II, III and IV. Significance: Our findings provide evidence that WPS inhalation triggers changes in liver morphology, oxidative stress, inflammation, DNA damage, apoptosis, and alterations in mitochondrial activity.

Cardiomyopathies (CMPs) encompass a heterogeneous group of cardiac disorders affecting mainly many of the elderly populations globally. Clinical presentation of cardiomyopathy varies among patients, based on the type and severity of the disorder. Preventing cardiomyopathy involves a multifaceted approach. Management strategies for cardiomyopathy encompass a spectrum of interventions. Medications, including beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, diuretics, and anti-arrhythmic drugs, are commonly prescribed to patients. Device implantation, including pacemakers, implantable cardioverter-defibrillators (ICDs), and ventricular-assist devices (VADs), is necessary in some cases. Lifestyle changes, including dietary modifications. Reduction in alcohol consumption, smoking and stress level, weight management, and regular exercise programmes, are essential components of adherence to self-care. Surgical interventions may be considered, including cardiac surgery and, in severe cases, heart transplantation. This review provides a thorough understanding of cardiomyopathy, covering a wide range of crucial aspects, including epidemiology, risk factors, types, subcellular and molecular mechanisms, clinical presentation, diagnostic approaches, treatment modalities, and prevention strategies, a profound understanding of these aspects is essential for healthcare professionals and researchers to enhance patient health care.

Recurrent dehydration causes chronic kidney disease in humans and animal models. The dromedary camel kidney has remarkable capacity to preserve water and solute during long-term dehydration. In this study, we investigated the effects of dehydration and subsequent rehydration in the camel's kidney histology/ultrastructure and changes in aquaporin/solute carrier proteins along with gene expression. In light microscopy, dehydration induced few degenerative and necrotic changes in cells of the cortical tubules with unapparent or little effect on medullary cells. The ultrastructural changes encountered in the cortex were infrequent during dehydration and included nuclear chromatin condensation, cytoplasmic vacuolization, mitochondrial swelling, endoplasmic reticulum/ lysosomal degeneration and sometimes cell death. Some mRNA gene expressions involved in cell stability were upregulated by dehydration. Lesions in endothelial capillaries, glomerular membranes and podocyte tertiary processes in dehydrated camels indicated disruption of glomerular filtration barrier which were mostly corrected by rehydration. The changes in proximal tubules brush borders after dehydration, were accompanied by down regulation of ATP1A1 mRNA involved in Na + /K + pump that were corrected by rehydration. The increased serum Na, osmolality and vasopressin were paralleled by modulation in expression level for corresponding SLC genes with net Na retention in cortex which were corrected by rehydration. Medullary collecting ducts and interstitial connective tissue were mostly unaffected during dehydration. CKD, a chronic nephropathy induced by recurrent dehydration in human and animal models and characterized by interstitial fibrosis and glomerular sclerosis, were not observed in the dehydrated/rehydrated camel kidneys. The initiating factors, endogenous fructose, AVP/AVPR2 and uric acid levels were not much affected. TGF-β1 protein and TGF-β1gene expression showed no changes by dehydration in cortex/medulla to mediate fibrosis. KCNN4 gene expression level was hardly detected in the dehydrated camel's kidney; to encode for Ca + + -gated KCa3.1 channel for Ca + + influx to instigate TGF-β1. Modulation of AQP 1, 2, 3, 4, 9 and SLC protein and/or mRNAs expression levels during dehydration/rehydration was reported. Long-term dehydration induces reversible or irreversible ultrastructural changes in kidney cortex with minor effects in medulla. Modulation of AQP channels, SLC and their mRNAs expression levels during dehydration/rehydration have a role in water conservation. Cortex and medulla respond differently to dehydration/rehydration.

Diabetes mellitus can induce substantial damage to the conduction system of the heart, especially the sinoatrial node. This is due to hyperglycemia leading to bradyarrhythmia. DM, via the elevation of HG, generates the production of a number of insulting agents in the myocardium known as reactive oxygen species and reactive carbonyl species, which elicit direct damage to neuro-filament-M and β2-adrenergic receptors in the conducting system as well as a number of cardiac contractile, cation transporting and channel proteins. One cation channel protein is the hyperpolarization-activated cyclic nucleotide-gated potassium channel. It encodes the protein responsible for the hyperpolarizing-activated current or the “funny current” that participates in spontaneous diastolic membrane depolarization in sinoatrial node cells. Gene expression of these proteins and their physiological functions are decreased in the diabetic heart, which affects the generation of electrical impulses or action potentials resulting in increases in RR and PR intervals and QRS complex duration of the electrocardiogram. The heart rate and force of contraction of the myocardium are decreased leading to bradyarrhythmia and sudden cardiac death. This review attempts to explain the cellular mechanism(s) involved in diabetes-induced bradyarrhythmia with emphasis on cation-transporting proteins, especially the hyperpolarization-activated cyclic nucleotide-gated channels pacemaker current channels.

Heart failure (HF) is characterized by ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, accelerated apoptosis, and genetic mutations. Current guidelines recommend using angiotensin receptor neprilysin inhibitor (ARNI) therapy for HF with reduced and preserved ejection fraction (HFpEF). Recent large-scale randomized clinical trials have confirmed the superiority of sacubitril/valsartan to other conventional drugs to treat HF. Growing evidence has revealed the cardioprotective effects of sacubitril/valsartan on cellular and molecular modulation in cardiac remodeling, although their molecular mode of action in cardiac remodeling is still unknown. An understanding of the molecular mechanism(s) of action of sacubitril/valsartan will therefore be helpful, but future research needs to be done to unravel the proper potential use of the drug in the treatment of HF. A meta-analysis of 16 studies involving 1937 patients found that ARNI was likely to improve left ventricular function by increasing left ventricular ejection fraction (LVEF) (WMD: 2.36, 95% CI: 1.09–3.62), stroke volume (WMD: 16.800, 95% CI: 11.385–22.215), left ventricular short-axis shortening rate (WMD: 2.05, 95% CI: 0.25–3.86), decreasing left ventricular end-diastolic dimension (WMD: −2.48, 95% CI: −3.83 to −1.13), left atrial diameter (WMD: −2.23, 95% CI: −2.83 to −1.63), C-reactive protein level (WMD: −1.40, 95% CI: −2.62 to −0.18), and N-terminal pro-B-type natriuretic peptide level (WMD: −494.92, 95% CI: −641.34 to −348.50). ARNI has a higher total effective rate (RR: 1.15, 95% CI: 1.08–1.21) via the Kansas City cardiomyopathy questionnaire (WMD: 4.13, 95% CI: 3.46–4.81), and 6-Minute Walk Test (WMD: 51.35, 95% CI: 26.99–75.71) compared with ACEI and ARB. In addition, ARNI decreased the readmission rate (RR: 0.54, 95% CI: 0.43–0.68) (all P<.05). There were no significant differences in the adverse outcomes, suggesting that ARNI may be an effective strategy for improving left ventricular function and quality of life, and reducing the readmission rate in patients with HF with mildly reduced ejection fraction.

Introduction: Brain histamine is considered an endogenous anticonvulsant and histamine H1 receptor. H1R antagonists have, in earlier studies, been found to induce convulsions. Moreover, research during the last two decades has provided more information concerning the anticonvulsant activities of histamine H3R (H3R) antagonists investigated in a variety of animal epilepsy models.Methods: Therefore, the in vivo anticonvulsant effect of the H3R antagonist DL76, with proven high in vitro affinity, in vitro selectivity profile, and high in vivo antagonist potency in mice against maximal electroshock (MES)-induced seizures in mice, was assessed. Valproic acid (VPA) was used as a reference antiepileptic drug (AED). In addition, DL76 was tested for its reproductive and fetal toxicity in the same animal species.Results and discussion: Our observations showed that acute systemic administration (intraperitoneal; i.p.) of DL76 (7.5 mg/kg, 15 mg/kg, 30 mg/kg, and 60 mg/kg, i.p.) provided significant and dose-dependent protection against MES-induced seizures in female and male mice. Moreover, the DL76-provided protective effects were comparable to those offered by the VPA and were reversed when animals were co-administered the CNS-penetrant selective H3R agonist R-(α)-methylhistamine (RAM, 10 mg/kg, i.p.). Furthermore, the administration of single (7.5 mg/kg, 15 mg/kg, 30 mg/kg, or 60 mg/kg, i.p.) or multiple doses (3 × 15 mg/kg, i.p.) of H3R antagonist DL76 on gestation days (GD) 8 or 13 failed to affect the maternal body weight of mice when compared with the control mice group. No significant alterations were detected in the average number of implantations and resorptions between the control and DL76-treated groups at the early stages of gestation and the organogenesis period. In addition, no significant differences in the occurrence of skeletal abnormalities, urogenital abnormalities, exencephaly, exomphalos, facial clefts, and caudal malformations were observed. The only significant abnormalities witnessed in the treated groups of mice were in the length of long bones and body length. In conclusion, the novel H3R antagonist DL76 protected test animals against MES-induced seizures and had a low incidence of reproductive and fetal malformation with decreased long bone lengths in vivo, signifying the potential therapeutic value of H3R antagonist DL76 for future preclinical as well as clinical development for use in the management of epilepsy.

Diabetes mellitus affects 537 million adults around the world. Adropin is expressed in different cell types. Our aim was to investigate the cellular localization in the endocrine pancreas and its effect on modulating pancreatic endocrine hormone release in streptozotocin (STZ)-induced diabetic rats. Adropin expression in the pancreas was investigated in normal and diabetic rats using immunohistochemistry and immunoelectron microscopy. Serum levels of insulin, glucagon pancreatic polypeptide (PP), and somatostatin were measured using a Luminex® χMAP (Magpix®) analyzer. Pancreatic endocrine hormone levels in INS-1 832/3 rat insulinoma cells, as well as pancreatic tissue fragments of normal and diabetic rats treated with different concentrations of adropin (10−6, 10−9, and 10−12 M), were measured using ELISA. Adropin was colocalized with cells producing either insulin, glucagon, or PP. Adropin treatment reduced the number of glucagon-secreting alpha cells and suppressed glucagon release from the pancreas. The serum levels of GLP-1 and amylin were significantly increased after treatment with adropin. Our study indicates a potential role of adropin in modulating glucagon secretion in animal models of diabetes mellitus.

Diabetes mellitus (DM) is a chronic metabolic disease marked by hyperglycemia due to insulin deficiency or insulin resistance leading to many chronic complications. It is thus important to manage diabetes effectively in order to prevent and or delay these complications. Melatonin is produced by the pineal gland and regulates the wake-sleep circadian rhythm. Existing evidence suggests that melatonin may be effective in the management of DM. However, the evidence on the mechanism of the beneficial effect melatonin as a treatment for DM is limited. In this study, we investigated the effect of melatonin treatment on blood glucose, insulin (INS), AKT and superoxide dismutase (SOD) gene levels in diabetic rats. Non-diabetic and diabetic rats were treated orally for 4 weeks with either 25 mg or 50 mg/kg body weight of melatonin. At the end of the study, pancreatic and liver tissues morphology, glucose homeostasis, serum insulin and SOD levels, hepatic gene and protein expression of SOD as protecting antioxidant enzyme and AKT as central element involved in PI3K/AKT insulin signaling pathway were estimated. Melatonin treated diabetic rats showed reduced hyperglycemia, and increased serum insulin and SOD levels. In addition, melatonin induced an increased gene and protein expression of SOD and AKT. In conclusion, melatonin may play a role in treating diabetic rats via stimulation of insulin secretion, insulin signaling and reduction in oxidative stress.

Lipids are primarily transported in the bloodstream by lipoproteins, which are macromolecules of lipids and conjugated proteins also known as apolipoproteins. The processes of lipoprotein assembly, secretion, transportation, modification, and clearance are crucial components of maintaining a healthy lipid metabolism. Disruption in any of these steps results in pathophysiological abnormalities such as dyslipidemia, obesity, insulin resistance, inflammation, atherosclerosis, peripheral artery disease, and cardiovascular diseases. By studying these genetic mutations, researchers can gain valuable insights into the underlying mechanisms that govern the relationship between protein structure and its physiological role. These lipoproteins, including HDL, LDL, lipoprotein(a), and VLDL, mainly serve the purpose of transporting lipids between tissues and organs. However, studies have provided evidence that apo(a) also possesses protective properties against pathogens. In the future, the field of study will be significantly influenced by the integration of recombinant DNA technology and human site-specific mutagenesis for treating hereditary disorders. Several medications are available for the treatment of dyslipoproteinemia. These include statins, fibrates, ezetimibe, niacin, PCSK9 inhibitors, evinacumab, DPP 4 inhibitors, glucagon-like peptide-1 receptor agonists GLP1RAs, GLP-1, and GIP dual receptor agonists, in addition to SGLT2 inhibitors. This current review article exhibits, for the first time, a comprehensive reflection of the available body of publications concerning the impact of lipoproteins on metabolic well-being across various pathological states.

Heart failure (HF) may have either an acute, gradual, or insidious onset, as in the case of hemodynamic pressure or volume overloading. This may be hereditary, as in the case of genetic cardiomyopathies. Cardiomyopathy is a disease with dysfunction of the myocardium due to the cardiac muscle protein abnormality with progressive cardiomyocyte loss leading to HF by means of either necrotic, apoptotic, or autophagic cell death pathways. There are two major types of intrinsic cardiomyopathies and they include hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), which are most often determined as genetic cardiomyopathies associated with HF. It seems that about 40%–60% of subjects with HCM and DCM have been recognized as genetic diseases with mutations in the sarcomere. A meta-analysis examined genome-wide association studies of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci were associated with HF, all of which demonstrated one or more associations with either coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, indicating shared genetic etiology. Functional analysis of non-CAD-associated loci implicates genes that are involved in cardiac development (MYOZ1, SYNPO2L), protein homeostasis (BAG3), and cellular senescence (CDKN1A). It is concluded that genetic analysis can provide improved diagnosis and management of HF with hereditary cardiomyopathy.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease affecting almost 30% of the world population. Approximately 25% of people with NAFLD develop nonalcoholic steatohepatitis (NASH), the fulminant version of the disease. Diabetes mellitus is present in 22.5% of people with NAFLD and 44.60% of individuals with NASH. This review was undertaken to examine the current contribution of glucagon-like peptide 1 (GLP-1) receptor agonists to the pharmacotherapy of diabetic nonalcoholic steatohepatitis. Areas covered: The author analyzed the current status of GLP-1 receptor agonists for pharmacotherapy of diabetic NASH. Research data and literature reports were taken from the database and or websites of Diabetes UK, American Diabetes Association, ClinicalTrials.gov, PubMed, and Scopus. The keywords utilized included type 2 diabetes, GLP-1, NASH, NAFLD, and clinical trials. Expert opinion: Since diabetic NASH is associated with obesity, diabetes mellitus, oxidative stress and inflammation, drugs capable of mitigating all of these conditions simultaneously, are most ideal for the treatment of diabetic NASH. These drugs include (in order of relevance), GLP-1 receptor agonists, GLP-1 and GIP dual receptor agonists, sodium-glucose co-transporter-2 (SGLT2) inhibitors, and pioglitazone. The future, FDA-approved drug for diabetic NASH treatment will likely be GLP-1 agonist, which could be used as monotherapy or in combination with other drugs.

Recent studies have implicated pre-beta and beta lipoproteins (VLDL and LDL) in the etiopathogenesis of complications of diabetes mellitus (DM). In contrast, alpha lipoprotein (HDL) is protective of the beta cells of the pancreas. This study examined the distribution of HDL in the islets of Langerhans of murine models of type 1 diabetic rats (streptozotocin (STZ)-induced DM in Wistar rats) and type 2 models of DM rats (Goto–Kakizaki (GK), non-diabetic Zucker lean (ZL), and Zucker diabetic and fatty (ZDF)). The extent by which HDL co-localizes with insulin or glucagon in the islets of the pancreas was also investigated. Pancreatic tissues of Wistar non-diabetic, diabetic Wistar, GK, ZL, and ZDF rats were processed for immunohistochemistry. Pancreatic samples of GK rats fed with either a low-fat or a high-fat diet were prepared for transmission immune-electron microscopy (TIEM) to establish the cytoplasmic localization of HDL in islet cells. HDL was detected in the core and periphery of pancreatic islets of Wistar non-diabetic and diabetic, GK, ZL, and ZDF rats. The average total of islet cells immune positive for HDL was markedly (<0.05) reduced in GK and ZDF rats in comparison to Wistar controls. The number of islet cells containing HDL was also remarkably (p < 0.05) reduced in Wistar diabetic rats and GK models fed on high-fat food. The co-localization study using immunofluorescence and TIEM techniques showed that HDL is detected alongside insulin within the secretory granules of β-cells. HDL did not co-localize with glucagon. This observation implies that HDL may contribute to the metabolism of insulin.