Ahmad A. Obaid

Background and Objectives: Studies in hypertension (HTN), migraine (MIG) and HTN associated MIG (HMIG) in women present a link between vascular disorders and migraine. However, there are controversial findings yet for the important factors involved in overweight (OW) women with HTN and HMIG in postmenopause (PMP). Therefore, we planned to investigate the interactive role of body mass index (BMI) based serum levels of interleukin-6 (IL-6) and vitamin D (VitD) in PMP women with HTN, and low frequency episodic MIG and HMIG with aura. Materials and Methods: The subject groups of normal weight normotensives (NW-NTN), OW-NTN, NW-HTN, OW-HTN, NW-MIG, OW-MIG, NW-HMIG and OW-HMIG in PMP women (n:1008) were studied for investigating the BMI based variations and associations of IL-6 and VitD. Age range in each PMP women group (n:126) was 51-60 years. BMI range respectively in NW and OW participants was ≥ 18.5 - ≤ 24.9 and ≥ 25 - ≤29.9 kg/m2. Results: Among groups variations indicated highly significant change in serum IL-6 and VitD. The post hoc Tukey Kramer test for HTN groups indicated significant increased VitD in OW-HTN compared to OW-NTN and NW-HTN, and significantly increased IL-6 in OW-HTN compared to OW-NTN and NW-HTN as well as OW-NTN compared to NW-NTN. Significant increased IL-6 was obtained in OW-MIG compared to NW-MIG and OW-HTN, NW-HMIG compared to NW-NTN, and OW-HMIG compared to OW-MIG, NW-HMIG and OW-NTN. The multiple linear regression indicated collective significant effect among BMI, IL-6, and VitD in OW-HTN, NW-MIG, OW-MIG, NW-HMIG and OW-HMIG. BMI and IL-6 presented significant inverse association with VitD in these groups. The remaining groups presented non-significant effect. Conclusion: Current study shows significant role of serum IL-6 and VitD in HTN and low-frequency episodic MIG and HMIG especially with OW status in PMP women. BMI based significant variation and negative association of IL-6 with vitamin D in HTN, and low-frequency episodic MIG and HMIG with aura in the present report provides evidence of the pathophysiological impact of IL-6 and vitamin D in HTN, and episodic MIG and HMIG.

Objectives: Cancer is a multifactorial disease determined by several factors. Metabolic disorders such as obesity and diabetes significantly contribute to cancer risk by promoting chronic inflammation, insulin resistance, and hormonal dysregulation. Obesity and hyperglycaemia elevate insulin-like growth factor-1 (IGF-1) levels, driving oncogenic pathways such as PI3K/Akt/mTOR, which promote tumour proliferation and survival. Furthermore, cancer cells undergo metabolic reprogramming, characterised by increased reliance on glycolysis (Warburg effect), facilitating tumour growth and therapy resistance. Hence, body weight reduction and glycaemic control may represent potential strategies for cancer prevention and treatment. Irisin, a myokine secreted by skeletal muscle, plays a critical role in cellular metabolism and energy homeostasis. Emerging evidence suggests that irisin may exert tumour-suppressive effects by modulating key metabolic and oncogenic pathways. Methods: A systematic literature search identified studies investigating irisin’s effects in various cancer models. Results: In vitro, irisin exerts dose- and time-dependent anti-proliferative effects in a variety of cancer cell lines, primarily via PI3K/Akt/mTOR inhibition and AMPK activation, leading to cell cycle arrest and apoptosis. Additionally, irisin inhibits epithelial–mesenchymal transition, which suppresses cancer cell migration and invasion. However, conflicting findings, particularly in hepatocellular carcinoma, suggest tissue-specific responses. Similarly, clinical data regarding systemic and tumoural irisin levels remain inconsistent and appear to vary based on cancer type and stage. Conclusions: Irisin represents a promising therapeutic target due to its ability to modulate metabolic and oncogenic pathways. However, further research is needed to elucidate its clinical relevance and optimise its application as an adjunct to existing cancer therapies.

Inflammatory Bowel Diseases (IBD), which encompass ulcerative colitis (UC) and Crohn’s disease (CD), are characterized by chronic inflammation and tissue damage of the gastrointestinal tract. This study aimed to uncover novel disease-gene signatures, dysregulated pathways, and the immune cell infiltration landscape of inflamed tissues. Eight publicly available transcriptomic datasets, including inflamed and non-inflamed tissues from CD and UC patients were analyzed. Common differentially expressed genes (DEGs) were identified through meta-analysis, revealing 180 DEGs. DEGs were implicated in leukocyte transendothelial migration, PI3K-Akt, chemokine, NOD-like receptors, TNF signaling pathways, and pathways in cancer. Protein–protein interaction network and cluster analysis identified 14 central IBD players, which were validated using eight external datasets. Disease module construction using the NeDRex platform identified nine out of 14 disease-associated genes (CYBB, RAC2, GNAI2, ITGA4, CYBA, NCF4, CPT1A, NCF2, and PCK1). Immune infiltration profile assessment revealed a significantly higher degree of infiltration of neutrophils, activated dendritic cells, plasma cells, mast cells (resting/activated), B cells (memory/naïve), regulatory T cells, and M0 and M1 macrophages in inflamed IBD tissue. Collectively, this study identified the immune infiltration profile and nine disease-associated genes as potential modulators of IBD pathogenesis, offering insights into disease molecular mechanisms, and highlighting potential disease modulators and immune cell dynamics.

Hyperphosphatasia with mental disorder (HPMRS) is a rare autosomal recessive disease caused by gene mutations in enzymes involved in the synthesis and remodeling of lipids. Seven-month-old boy diagnosed with bilateral glaucoma had a cleft palate, facial dysmorphism, hypertelorism, a broad nasal bridge, and large fleshy earlobes. A brain MRI scan also revealed brain abnormalities. The observed phenotype in a seven-month-old boy is in agreement with the phenotypic features of HPRMS type-4. Whole exome sequencing revealed a possible pathogenic variant of PGAP3 in a homozygous state (c.320C>T, p.Ser107Leu) which supported the diagnosis of HPRMS type-4. We report an unusual presentation for HPMRS and suggest adding this syndrome to the list of differential diagnoses of syndromic congenital glaucoma.

Aim: Vitamin D deficiency is linked with type 2 diabetes mellitus (T2DM) and the occurrence of complications in patients with type 2 diabetes mellitus. None of the studies have focused on the association between vitamin D levels in patients with type 2 diabetes mellitus and diabetic nephropathy (DN) in the Makkah region, Saudi Arabia. Hence, the purpose of this study is to investigate the relationship of vitamin D with kidney disease in patients with T2DM in the Makkah region, of Saudi Arabia. Materials and Methods: This descriptive cross-sectional study was conducted at different hospitals in the Makkah region on T2DM patients from 2021 to 2022. In total, 328 patients with confirmed diabetes were enrolled in this study. T2DM patients over the aged> 18 to 92 years were included in the study. General laboratory characteristics of the study population were measured, including fasting blood sugar, HbA1C (Glycated hemoglobin), vitamin D, kidney function (BUN-Blood urea nitrogen and creatinine), and lipid profiles (cholesterol, triglycerides, LDL-Low density lipoprotein, and HDL-High density lipoprotein). Results: 46.6% (n=153) of participants had normal serum vitamin D levels. Insufficient and deficient serum vitamin D level were observed in 43.9% (n=144) and 9.5% (n=31) of participants, respectively. Of the participants, 25.9% (n=85) had good glycemic control (< 7.0%). Moderate and poor glycemic control were observed in 39.9% (n=131) and 34.1% (n=112) of the participants, respectively. A significant negative correlation (p< 0.5) was found between vitamin D levels and kidney function test results (blood urea nitrogen and serum creatinine levels). An inverse relationship was observed between HbA1c levels and vitamin D deficiency. Conclusion: Nephropathy is more likely to develop in people with type 2 diabetes mellitus and vitamin D deficiency.

Herein, we measured the antidiabetic and nephroprotective effects of the sodium–glucose cotransporter-2 inhibitor (empagliflozin; SGLT2i) and synthetic active vitamin D (paricalcitol; Pcal) mono- and co-therapy against diabetic nephropathy (DN). Fifty mice were assigned into negative (NC) and positive (PC) control, SGLT2i, Pcal, and SGLT2i+Pcal groups. Following establishment of DN, SGLT2i (5.1 mg/kg/day) and/or Pcal (0.5 µg/kg/day) were used in the designated groups (5 times/week/day). DN was affirmed in the PC group by hyperglycaemia, dyslipidaemia, polyuria, proteinuria, elevated urine protein/creatinine ratio, and abnormal renal biochemical parameters. Renal SREBP-1 lipogenic molecule, adipokines (leptin/resistin), pro-oxidant (MDA/H₂O₂), pro-inflammatory (IL1β/IL6/TNF-α), tissue damage (iNOS/TGF-β1/NGAL/KIM-1), and apoptosis (TUNEL/Caspase-3) markers also increased in the PC group. In contrast, renal lipolytic (PPARα/PPARγ), adiponectin, antioxidant (GSH/GPx1/SOD1/CAT), and anti-inflammatory (IL10) molecules decreased in the PC group. Both monotherapies increased insulin levels and mitigated hyperglycaemia, dyslipidaemia, renal and urine biochemical profiles alongside renal lipid regulatory molecules, inflammation, and oxidative stress. While SGLT2i monotherapy showed superior effects to Pcal, their combination demonstrated enhanced remedial actions related to metabolic control alongside renal oxidative stress, inflammation, and apoptosis. In conclusion, SGLT2i was better than Pcal monotherapy against DN, and their combination revealed better nephroprotection, plausibly by enhanced glycaemic control with boosted renal antioxidative and anti-inflammatory mechanisms.

Autoimmune diseases, characterized by the immune system’s loss of self-tolerance, lack definitive diagnostic tests, necessitating the search for reliable biomarkers. This systematic review aims to identify common metabolite changes across multiple autoimmune diseases. Following PRISMA guidelines, we conducted a systematic literature review by searching MEDLINE, ScienceDirect, Google Scholar, PubMed, and Scopus (Elsevier) using keywords “Metabolomics”, “Autoimmune diseases”, and “Metabolic changes”. Articles published in English up to March 2023 were included without a specific start date filter. Among 257 studies searched, 88 full-text articles met the inclusion criteria. The included articles were categorized based on analyzed biological fluids: 33 on serum, 21 on plasma, 15 on feces, 7 on urine, and 12 on other biological fluids. Each study presented different metabolites with indications of up-regulation or down-regulation when available. The current study’s findings suggest that amino acid metabolism may serve as a diagnostic biomarker for autoimmune diseases, particularly in systemic lupus erythematosus (SLE), multiple sclerosis (MS), and Crohn’s disease (CD). While other metabolic alterations were reported, it implies that autoimmune disorders trigger multi-metabolite changes rather than singular alterations. These shifts could be consequential outcomes of autoimmune disorders, representing a more complex interplay. Further studies are needed to validate the metabolomics findings associated with autoimmune diseases.

Natural antioxidants derived from plants have played a vital role in preventing a wide range of human chronic conditions and provide novel bioactive leads for investigators in pharmacotherapy discovery. This work was designed to examine the ethnopharmacological role of Urtica dioica (UD), Capsella bursa-pastoris (CBP), and Inula racemosa (IR). The total phenolic and flavonoid contents (TPC and TFC) were illustrated through colorimetric assays, while the antioxidant activity was investigated through DPPH and ABTS assays. The evaluation of phytochemicals by FT-IR of UD and CBP revealed high contents of aliphatic amines, while IR showed a major peak for ketones. The antioxidant activity, TPC and TFC were highest in the ethanol extract of UD, followed by CBP, and IR showed the lowest activity. All of the extracts revealed significant antioxidant capacities along a dosage gradient. Through a HPLC analysis at a wavelength of 280 nm, UD leaves demonstrated an intense peak of quercetin, and the peak for rutin was less intense. CBP (whole plant), instead, demonstrated a major yield of rutin, and a peak for quercetin was not observed in CBP. IR (rhizomes) showed both quercetin and rutin. All of the extracts were significantly cytotoxic to HepG2 cells after 48 h with the trend IR > UD > CBP. The outcomes of this study may be effective in the selection of specific plants as realistic sources of the bioactive components that might be useful in the nutraceutical progression and other biomedical efficacies.

Aging constitutes progressive physiological changes in an organism. These changes alter the normal biological functions, such as the ability to manage metabolic stress, and eventually lead to cellular senescence. The process itself is characterized by nine hallmarks: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These hallmarks are risk factors for pathologies, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Emerging evidence has been focused on examining the genetic pathways and biological processes in organisms surrounding these nine hallmarks. From here, the therapeutic approaches can be addressed in hopes of slowing the progression of aging. In this review, data have been collected on the hallmarks and their relative contributions to aging and supplemented with in vitro and in vivo antiaging research experiments. It is the intention of this article to highlight the most important antiaging strategies that researchers have proposed, including preventive measures, systemic therapeutic agents, and invasive procedures, that will promote healthy aging and increase human life expectancy with decreased side effects.