Pakistan BioMedical Journal

Association Between Gestational Diabetes Mellitus and Maternal Bone Metabolism: A Cross-Sectional Study

2026-02-10T10:18:10+00:00

Gestational diabetes mellitus (GDM) is a prevalent metabolic condition complicated by pregnancy that relates to poor maternal and infant outcomes. The connection between glucose intolerance and a shift in the bone metabolism in pregnant women is a developing field whose applicability of bone turnover measurements in GDM is yet to be determined. Objectives: To determine the relationship between GDM and maternal bone turnover indices and GDM predictors. Methods: The groups of pregnant women with GDM and those without diabetes were 120 and 60, respectively, in the second trimester of this cross-sectional study. Serum osteocalcin, a cross-linked C-telopeptide of type I collagen (CTX), and bone-specific alkaline phosphatase (B-ALP) were measured. It comprised a series of clinical, biochemical, and obstetric data, such as the body mass index (BMI) and insulin resistance, which was determined using the homeostasis model assessment (HOMA-IR). ROC curve analysis and logistic regression analysis were carried out. Results: GDM women were significantly older women with much higher BMI and HOMA-IR compared to controls (p<0.001). B-ALP level of the GDM group was substantially low (p<0.05), and CTX did not change. The results of the logistic regression analysis identified the independent predictors of GDM as osteocalcin, BMI, and HOMA-IR (OR: 0.565; 0.442-0.722; OR: 1.309; 1.062-1.614; OR: 2.289; 1.090-4.805). The discriminative power (AUC = 0.905; p<0.001) was found to be powerful. Conclusions: GDM is also related to bone metabolism, osteocalcin, BMI, and HOMA-IR are independent predictors.

Association of CYP19A1 Gene Polymorphism with Male Infertility in Khyber Pakhtunkhwa Population, Pakistan

2026-02-10T10:18:06+00:00

Male infertility is a multifactorial disease that is controlled by genetic, hormonal, and semen factors. In this research, the authors examined the relationship that exists between the CYP19A1 gene polymorphisms, semen parameters, and hormone profiles in male infertility. Objectives: To determine the Polymorphism CYP19A1 Gene and Male Infertility among the Khyber Pakhtunkhwa Population, Pakistan. Methods: 186 men were recruited into the study, consisting of 106 infertile men and 80 healthy controls. Sanger sequencing was done on three CYP19A1 SNPs (rs17703883, rs726546, and rs10046). ELISA was used to determine serum hormonal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and testosterone, and semen parameters, such as sperm count, morphology, and motility. Results: Genotype and allele frequency analysis showed a significant relationship between male infertility and the polymorphisms of the following: rs 17703883 and rs 726546, and not the polymorphism of rs10046 (p>0.05). Nonetheless, none of the SNPs that were researched were significantly correlated with serum testosterone levels. Conclusions: These observations indicate that the same CYP19A1 gene (rs17703883 and rs726546) might have an implication on male infertility among this population, but they do not seem to be the cause of lowered serum testosterone. More research with an increased sample size and functional studies needs to be done to elucidate the functions of these variants. Additional studies on the genetic role of oestrogen metabolism in the occurrence of male infertility need larger samples and other functional variants of CYP19A1.

Innovative Therapeutic Paradigms in Diabetes Mellitus: Current Progress and Future Directions

2026-02-10T10:18:09+00:00

Diabetes mellitus is a chronic metabolic disease that is marked by inadequate glucose control that leads to eventual complications in the cardiovascular, renal, neurological, and ocular systems. The conventional approaches to treatment, such as insulin injections, oral hypoglycemic drugs, and structured lifestyle changes, continue to be the predominant approaches to treatment. However, the techniques are commonly limited so as to contain the symptoms and not achieve a long-lasting remission or to cure the causes of the disease. This has altered the field of science in the recent past, where creative approaches towards treatment have been given focus to change or even reverse the stages of disease. Stem cell interventions have the potential to cure pancreatic β-cells, and genetic therapy is meant to fix the genetic defects that lead to the disease. Immunotherapy transplantation is being undertaken to protect the β-cells in diabetes type 1 diabetes, and nanotechnology and smart insulin delivery systems can provide more precise glycemic control. In addition, the intestinal microbiota modulation has also become one of the promising adjunctive mechanisms. This review gives these new methodologies, the current status of these methodologies, and the possibilities of these methodologies in the management of diabetes.

Agonists and Antagonists of Peptide Receptors: Therapeutic Approaches to Combat Cancer

2026-02-10T10:18:08+00:00

Despite the significant advances made in cancer diagnosis and treatment, much remains to be learned and explored. New strategies and lines of research must be pursued, in combination with those currently used (surgery, radiotherapy, chemotherapy, immunotherapy). Peptidergic systems are involved in many physiological functions and are also implicated in many human pathologies, including cancer. There is increasing research on these systems in relation to cancer development and progression, peptide receptor overexpression, biomarkers, prognosis, aggressiveness, relapse risk, and tumor size. Endogenous bioactive peptides exert oncogenic actions (e.g., cell proliferation and migration, anti-apoptotic action, angiogenesis) and antitumor effects (counteracting previous mechanisms). These bioactive peptides bind to peptide receptors that are overexpressed in cancer cells compared to normal cells. This is crucial for establishing more specific therapeutic strategies using antitumor peptides and oncogenic peptide antagonists, since these antagonists produce antitumor effects, including the apoptosis of tumor cells which is greater in tumor cells than in normal cells. Therefore, the co- administration of antitumor agonists and oncogenic peptide antagonists is a very promising anticancer line of research that needs to be developed. This treatment would not depend on either the clinical state or the biology of the tumor, since by overexpressing peptide receptors different tumors (e.g., glioma, lung cancer, hepatoblastoma, breast cancer), they could be treated with the same antitumor therapeutic procedure. What data currently exists to support what was written above and what peptide receptor agonists and antagonists act as antitumor agents? Fortunately, there is very promising data, some examples: 1) Neurokinin receptor antagonists: Aprepitant (Emend, neurokinin-1 receptor antagonist) exerts a broad antitumor action against numerous types of cancer (breast, pancreas, liver, lung, larynx, prostate, glioma, neuroblastoma, retinoblastoma, osteosarcoma, melanoma, thyroid, gastric, colon, leukemia) and the repurposing of this antiemetic used in clinical practice as an anticancer agent has been suggested [1]; 2) Angiotensin II receptor antagonists: Telmisartan and losartan (DuP-753, angiotensin II type 1 receptor antagonists) and PD-123,177, PD-123,319 ditrifluoroacetate, olodanrigan (EMA401) and A3E (angiotensin II type 2 receptor antagonists) exert an anticancer action against glioma and neuroblastoma [2]; 3) Neurotensin receptor antagonists: SR- 48692 and meclinertant (SR-48692) (neurotensin type 1 receptor antagonists) against glioma and ovarian cancer [2]; 4) Bradykinin receptor antagonists: SSR-240,612 (bradykinin type 1 receptor antagonist), Firazyr (HOE-140, bradykinin type 2 receptor antagonist), and BKM-570 (mainly a bradykinin type 2 receptor antagonist) against glioma [2]; 5) Vasopressin receptor antagonists: Tolvaptan (vasopressin type 2 receptor antagonist) against neuroblastoma [3]; 6) Neuropeptide Y receptor antagonists: BIBP- 3226 (neuropeptide type 1 receptor antagonist), BIIE-0246 (neuropeptide type 2 receptor antagonist) and L-152,804 (neuropeptide type 5 receptor antagonist) exert anticancer actions against neuroblastoma and breast, colon and prostate cancer [4]; 7) Galanin receptor antagonists: SNAP-37889 (HT-2157, galanin type 3 receptor antagonist) acts against leukemia [5], and 8) Glucagon-like peptide-1 receptor agonists, galanin type 2 receptor agonists (M89b) and angiotensin II type 2 receptor agonists also exert antitumor effects against pancreatic and colorectal cancer [6]. And there is something else, and it is very important: Somatostatin peptide analogs and gonadotropin-releasing hormone receptor agonists (triptorelin, lupron, zoladex (goserelin)) are currently used in clinical practice to fight lung, prostate, breast and neuroendocrine tumors [7]. These are some examples of the great antitumor potential of peptide receptor agonists and antagonists, alone or in combination with current therapies. In sum, peptide receptors are promising anticancer therapeutic targets and its exhaustive study will improve the diagnosis, management and treatment of tumors.