Hafiz Ahmed

Nanomaterials (NMs) offer substantial technological advantages, yet their potential adverse biological effects remain a critical concern. This study investigates the maternal–fetal toxicity of zinc oxide nanoparticles (ZnONPs) following a single intravenous (i.v.) administration in vivo, focusing on oxidative DNA damage, cytotoxicity, and transplacental transfer. The median lethal dose (LD₅₀) of ZnONPs was determined to be 154 mg/kg of body weight. Pregnant rats on gestational day 19 were exposed to two sub-lethal doses (3.09 and 7.71 mg/kg; corresponding to 1/50 and 1/20 of LD50). Subsequent analyses assessed Zn²⁺ accumulation, histopathological alterations in maternal organs, and induction of 8-hydroxydeoxyguanosine (8-OHdG) in maternal and fetal tissues. ZnONPs demonstrated systemic distribution, with pronounced accumulation in the liver, spleen, and placenta, and were shown to cross the placental barrier, leading to fetal exposure. Elevated Zn²⁺ concentrations were positively correlated with cytotoxicity and 8-OHdG induction across maternal and fetal compartments. These findings provide compelling evidence of ZnONPs-mediated cyto- and genotoxicity in both mothers and offspring, underscoring the need to define safety margins and regulatory thresholds for nanomaterial exposure in biomedical and environmental contexts.

The widespread biomedical and commercial applications of silver nanoparticles (AgNPs) have increased their potential for human and environmental exposure and toxicity to human health. The bio-distribution and toxicity of AgNPs in rodents following inhalation, intratracheal instillation, and oral ingestion are well documented; however, little is known about the bio-distribution of intravenously (IV)-administered AgNPs and their organ-specific pathophysiological effects. Here, we investigate the pharmacokinetic pattern and tissue distribution of AgNPs in male rats following IV administration. The animals were humanely sacrificed after 10 min, 1 h, 6 h, 12 h, 24 h, and 168 h of AgNP administration, and the silver (Ag) content was measured from blood samples and various tissues following acid digestion. The AgNPs were readily absorbed and subsequently distributed into most organs predominantly in the colon, small intestine, kidney, and heart after 6 h; however, they were the highest in the spinal cord after 168 h. White blood cells (WBCs) were significantly increased (42–60%) in AgNP-administered animals at all time points except 10 min. Regarding platelets, all AgNP-administered animals showed counts 7.8–39.2% lower, with the lowest count at 168 h post-administration. In the case of lymphocytes (LYMs), the AgNP-treated animals exhibited a count 19.5–41% lower at 10 min and 1 h post-administration; however, the animals at 168 h post-administration showed a count 30.5% more. The mean corpuscular hemoglobin (MCH) counts from the AgNP-treated animals were decreased by 50–62%. The concentrations of aspartate transaminase (AST), urea, and creatinine were increased in the AgNP-treated animals. Taken together, the results suggest that the acute IV administration of AgNPs alters metabolic and hematological parameters in animals and may pose a health risk to humans.

Galectin-3 (Gal3) is one of the most studied members of the galectin family that mediate various biological processes such as growth regulation, immune function, cancer metastasis, and apoptosis. Since Gal3 is pro-inflammatory, it is involved in many diseases that are associated with chronic inflammation such as cancer, organ fibrosis, and type 2 diabetes. As a multifunctional protein involved in multiple pathways of many diseases, Gal3 has generated significant interest in pharmaceutical industries. As a result, several Gal3-targeting therapeutic drugs are being developed to address unmet medical needs. Based on the PubMed search of Gal3 to date (1987–2023), here, we briefly describe its structure, carbohydrate-binding properties, endogenous ligands, and roles in various diseases. We also discuss its potential antagonists that are currently being investigated clinically or pre-clinically by the public and private companies. The updated knowledge on Gal3 function in various diseases could initiate new clinical or pre-clinical investigations to test therapeutic strategies, and some of these strategies could be successful and recognized as novel therapeutics for unmet medical needs.

Cancer is a fatal disease worldwide. Each year ten million people are diagnosed around the world, and more than half of patients eventually die from it in many countries. A majority of cancer remains asymptomatic in the earlier stages, with specific symptoms appearing in the advanced stages when the chances of adequate treatment are low. Cancer screening is generally executed by different imaging techniques like ultrasonography (USG), mammography, CT-scan, and magnetic resonance imaging (MRI). Imaging techniques, however, fail to distinguish between cancerous and non-cancerous cells for early diagnosis. To confirm the imaging result, solid and liquid biopsies are done which have certain limitations such as invasive (in case of solid biopsy) or missed early diagnosis due to extremely low concentrations of circulating tumor DNA (in case of liquid biopsy). Therefore, it is essential to detect certain biomarkers by a noninvasive approach. One approach is a proteomic or glycoproteomic study which mostly identifies proteins and glycoproteins present in tissues and serum. Some of these studies are approved by the Food and Drug Administration (FDA). Another non-expensive and comparatively easier method to detect glycoprotein biomarkers is by ELISA, which uses lectins of diverse specificities. Several of the FDA approved proteins used as cancer biomarkers do not show optimal sensitivities for precise diagnosis of the diseases. In this regard, expression of phosphoproteins is associated with a more specific stage of a particular disease with high sensitivity and specificity. In this review, we discuss the expression of different serum phosphoproteins in various cancers. These phosphoproteins are detected either by phosphoprotein enrichment by immunoprecipitation using phosphospecific antibody and metal oxide affinity chromatography followed by LC-MS/MS or by 2D gel electrophoresis followed by MALDI-ToF/MS analysis. The updated knowledge on phosphorylated proteins in clinical samples from various cancer patients would help to develop these serum phophoproteins as potential diagnostic/prognostic biomarkers of cancer.

The ultimate goal of cancer science is to learn how to select a cancer cell surface. Glycans in cancer cells are frequently at varying quantities or have fundamentally various structures than those seen in normal cells. The presence of sialic acid (Neu5Ac), which is prevalent at the end of glycan chains, is significant. N-glycolylneuraminic acid (Neu5Gc) is a “non-human” sugar type that intercept into Neu5Ac natural biosynthetic machinery, presaging as a perspective biomarker. Malignant breast cells resistance to chemotherapy and their non-malignant counterparts, when treated with the Neu5Gc under nutrient deprivation, display cell surface tumor-associated Neu5Gc-rich glycans, which is capture with Neu5Gc linkage specific plant lectins such as Triticum vulgaris agglutinin (WGA), Sambucus nigra agglutinin (SNA), and Maackia amurensis agglutinin I (MAL-I). Nevertheless, MAL-I binding differentiates surface of malignant breast cell line resistance to chemotherapy MCF-7/H compared to normal mammary epithelial cell line MCF-10/A. These findings emphasize the importance of one oxygen atom in Neu5Gc; it’s supplementing of nutrient-depleted cancer cells' resistance to chemotherapy and facilitates the way for the implementation of better diagnostic and prognostic approaches.

Background: It has been suggested that the laparoscopic approach is associated with a reduction in operative morbidity. Over the last two decades there has been a steady increase in the use of laparoscopy for endometrial cancer. This review investigated the evidence of benefits and harms of laparoscopic surgery with implementation of ERAS program, versus traditional laparotomy for presumed early stage endometrial cancer. Study objective: To study the efficacy of laparoscopic radical hysterectomy with implementation of ERAS protocol for treatment of endometrial cancer on operative outcome and overall survival in comparison with traditional abdominal hysterectomy. Selection criteria: Non randomized controlled trial comparing laparoscopy with ERAS and laparotomy with mechanical bowel preparation for treatment of early stage endometrial cancer. Data collection and analysis: The study was done in El- Salam Oncology center, Cairo and Minia maternity university hospital (MMUH), Egypt. The study included two groups of patients diagnosed as endometrial carcinoma ( stage I) prepared for operations. First group (27 patients ) managed with laparoscopy with implementation of ERAS protocol while the other group (31 patients) managed with conventional laparatomy. Results: There was statistically significant reduction in action group than in conventional group as regarding : LOS (2.15 + 0.71 Vs 0.39+ 0.80), reduction in post operative pain which assessed by VAS score ( 3.04 +1.05) vs ( 5.71 + 1.00) and post operative fluid balance (916.67ml) vs ( 2345.16 ml). There was statistically insignificant difference between both groups in postoperative pneumonia, urinary tract infection, surgical site infection. As a result readmission to hospital was less in active group than conventional (2 vs 8patients). Conclusion: Implementation of ERAS protocol in gynecologic surgery for endometrial carcinoma tailored according to the situation in each case, But in general; use of laparoscopy with ERAS was associated with controlled intravenous fluids utility, comparable pain, better operative outcome with less complication rates compared to conventional laparotomy.

Metastatic colorectal cancer (mCRC) is characterized by the expression of cellular oncogenes, the loss of tumor suppressor gene function. Therefore, identifying integrated signaling between onco-suppressor genes may facilitate the development of effective therapy for mCRC. To investigate these pathways we utilized cell lines and patient derived organoid models for analysis of gene/protein expression, gene silencing, overexpression, and immunohistochemical analyses. An inverse relationship in expression of oncogenic FoxM1 and tumor suppressor RASSF1A was observed in various stages of CRC. This inverse correlation was also observed in mCRC cells lines (T84, Colo 205) treated with Akt inhibitor. Inhibition of FoxM1 expression in mCRC cells as well as in our ex vivo model resulted in increased RASSF1A expression. Reduced levels of RASSF1A expression were found in normal cells (RWPE-1, HBEpc, MCF10A, EC) stimulated with exogenous VEGF₁₆₅. Downregulation of FoxM1 also coincided with increased YAP phosphorylation, indicative of tumor suppression. Conversely, downregulation of RASSF1A coincided with FoxM1 overexpression. These studies have identified for the first time an integrated signaling pathway between FoxM1 and RASSF1A in mCRC progression, which may facilitate the development of novel therapeutic options for advanced colon cancer therapy.

Tunicamycin induced endoplasmic reticulum stress promotes apoptosis of prostate cancer cells by activating mTORC1 Tunicamycin induced endoplasmic reticulum stress promotes apoptosis of prostate cancer cells by activating mTORC1