Biomedical Research and Therapy

Assessment of thyroid profile and mineral status in patients with hypothyroidism – A hospital based case-control study

Neelayathatchi Ramesh — 2025-02-28

Introduction: Thyroid hormones are major contributors to numerous physiological processes in the body. Thyroid disorders are frequently associated with an imbalance in the homeostasis of calcium and phosphorus. The objective of this study is to evaluate and compare the mineral status of hypothyroid patients and euthyroid controls by determining the serum levels of calcium, magnesium, and phosphorus. The aim is to identify any significant differences in the concentrations of these minerals between hypothyroid individuals and healthy controls, thereby contributing to a better understanding of the potential metabolic disturbances associated with hypothyroidism.

Methods: A prospective case-control study was conducted at Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu. It involved 35 hypothyroidism cases and 35 euthyroid controls attending the outpatient department, aged 18-45 years. The control group had normal Thyroid-Stimulating Hormone (TSH) and Free Thyroxine (FT4) levels, while the case group had hypothyroidism, diagnosed by increased TSH levels and decreased FT4. Serum samples were evaluated for TSH, Free Triiodothyronine (FT3), FT4, calcium, magnesium, and phosphorus in both case and control groups.

Results: Serum calcium levels were found to be significantly decreased (p<0.001) and serum magnesium and phosphorus were found to be slightly elevated (p>0.05) in the hypothyroid cases compared to euthyroid controls. Calcium positively correlated with FT3 and negatively correlated with FT4, while phosphorus levels positively correlated with TSH levels and negatively correlated with FT4, calcium, and magnesium levels.

Conclusion: Hypothyroid individuals have an altered mineral profile, necessitating comprehensive treatment procedures and monitoring of serum levels. Early assessment of mineral status in terms of calcium, magnesium, and phosphorus can aid in the treatment and management of hypothyroidism, preventing further complications.

The diagnostic value of liquid-based cytology of pleural fluid in malignant pleural effusion: A prospective study

Nam Vu-Hoai — 2025-02-28

Introduction: Pleural effusion (PE) is commonly observed in clinical practice. Conventional smear (CS), cell block (CB), and liquid-based cytology (LBC) of pleural fluid are used to guide the diagnosis of malignant pleural effusion (MPE). However, the effectiveness of these cytological techniques, whether used alone or in combination, is still not well established.

Methods: A prospective study was conducted from October 2019 to May 2020 at the Department of Pulmonary Medicine, Cho Ray Hospital (Ho Chi Minh City, Vietnam). Suspected MPE patients were investigated by simultaneous cytological methods (CS, CB, and LBC) of pleural fluid and pleural tissue histopathology. The study included 47 patients with MPE, confirmed by pleural tissue pathology as the gold standard. The study compares the sensitivity of the three cytological methods.

Results: Out of 69 patients suspected of MPE, 47 were confirmed to have MPE through histopathological analysis of pleural biopsy. The average age of the study participants was 62.6 years, with 44.7% being male. The sensitivity of LBC and CB, LBC and CS, and CB and CS did not significantly differ, with p-values of 0.546, 0.789, and 0.606, respectively (McNemar test). Combining two of the three cytological methods (CS, CB, LBC) significantly enhances the sensitivity in diagnosing MPE compared to using a single method alone, except for the combination of CB and LBC versus LBC alone. The study has limitations, including the exclusion of non-MPE pleural effusion cases, which means the specificity of the cytological methods could not be calculated. Additionally, the limited number of patients should be taken into consideration, and caution is advised when interpreting the study results.

Conclusions: The study concludes that CS, CB, and LBC methods have similar sensitivity in diagnosing MPE. Combining any two methods improves diagnostic sensitivity compared to using a single method, although CB and LBC together do not surpass LBC alone. Clinicians should consider combining cytological techniques to optimize the diagnostic sensitivity of MPE.

Exploring the therapeutic potential of naringin and melatonin in breast cancer: A focus on SKBR3 and MCF-7 cell lines

Milad Azizpour — 2025-02-28

Introduction: Breast cancer is a significant global health issue, particularly in women, and is the fifth leading cause of cancer-related deaths in Iran. This study investigates the anticancer effects of naringin and melatonin on SKBR3 (HER2⁺) and MCF-7 (HER2^-) breast cancer cell lines.

Methods: Cell viability and cytotoxicity were assessed using the MTT assay, which measures the reduction of MTT to formazan by mitochondrial dehydrogenase enzymes in viable cells. Cells were treated with various concentrations of naringin and melatonin. Antioxidant enzyme activities of SOD and LDH were measured, and lipid peroxidation was assessed by MDA levels. Statistical analysis was performed using SPSS and GraphPad Prism software, with significance set at p < 0.05.

Results: Both compounds showed a dose-dependent reduction in cell viability and increased cell death in both cell lines. Naringin significantly decreased SOD activity while increasing LDH activity and MDA levels. Similarly, melatonin treatment led to increased cell death, elevated MDA levels, and higher LDH activity, coupled with a decrease in SOD activity.

Conclusion: The findings indicate that naringin and melatonin have potent anticancer properties. Their ability to induce oxidative stress and modulate antioxidant defenses suggests their potential as therapeutic agents in breast cancer treatment. Further research and clinical applications are warranted to explore their efficacy in combating breast cancer. Both compounds exhibit significant anticancer properties against breast cancer cell lines, SKBR3 and MCF-7, making them promising candidates for further study.

Computational design and evaluation of a novel temporin 1CEa-IL24 fusion protein for anti-tumor potential

Hafiz Muhammad Rehman — 2025-02-28

Introduction: Synthetic fusion proteins represent a cutting-edge approach in biotechnology and pharmaceutical research, enabling the strategic combination of multiple protein domains to design novel complexes with enhanced properties and functionalities. By fusing distinct proteins, the unique attributes of each component can be synergistically exploited, leading to improved bioactivities or the emergence of entirely new functions. This study aimed to computationally construct a fusion protein that contained the killing properties of temporin 1CEa and the targeting action of IL-24, joined via a rigid linker, and its anti-tumor potential was analyzed using different bioinformatics tools.

Methods: After sequence retrieval, the 3D model of the temporin 1CEa-IL-24 fusion protein was constructed using the AlphaFold 2 online server. The resulting structure underwent rigorous refinement, quality assessment, and validation processes. Physiochemical properties were evaluated using ProtParam, and the prepared structure was subjected to docking on ClusPro and simulation on VMD and NAMD.

Results: Assessment through ERRAT score and Ramachandran plot analysis confirmed the good quality, refinement, and validation of the 3D structure of the temporin 1CEa-IL-24 fusion protein. Docking results revealed 17 hydrogen bonds and 4 salt bridges between the fusion protein and its receptor, findings supported and validated through simulation studies predicting a stable docked complex over a 100 ns period.

Conclusion: The expression of the temporin 1CEa-IL-24 fusion gene in a suitable expression host could lead to in vitro production and subsequently validate its therapeutic potential.

Cytotoxicity and antiproliferative activity of Arctium lappa extract on an in vitro model of human colorectal cancer

Amal I. Hassan — 2025-02-28

Background : Natural remedies are an excellent source for screening innovative and safe anti-cancer medicines. This study is intended to explore the potential toxicity of burdock seed extract, Arctium lappa (A. lappa), as well as its anti-regenerative and anti-proliferative effects on tumor cells in vitro.

Methods: The antiproliferative effect of A. lappa ethanol extract (EtOH) was evaluated on human colorectal carcinoma (H-COLO-205) cells and normal skin fibroblast (HSF) cell lines using the SRB assay. Matrix metalloproteinases (MMP-2 and MMP-9) and apoptotic gene expressions (e.g., BAX, BCL-2, P53) were analyzed using Western blot and qRT-PCR, respectively.

Results: A. lappa inhibited H-COLO-205 cell growth with an IC₅₀ of 11.80 µg/mL while sparing normal HSF cells (IC₅₀ = 1485 µg/mL). The extract significantly increased pro-apoptotic gene expression, with upregulation of caspase-3 (4.07-fold), caspase-9 (3.66-fold), P53 (2.69-fold), and BAX (22.44-fold), and downregulated the anti-apoptotic gene BCL-2 by 13.33-fold. Migration assays showed that A. lappa reduced MMP-2 and MMP-9 protein levels by 1.36-fold and 1.34-fold, respectively. The extract also downregulated NF-κB expression and significantly decreased the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α. Furthermore, A. lappa enhanced DNA fragmentation, with a 4.36% increase in comet tail migration and an 18.88 tail moment at a 100 µg/mL concentration. Molecular docking revealed that arctigenin, a major compound in A. lappa, forms stabilizing hydrogen bonds with TGF-βR1, inhibiting its kinase function and associated cancer pathways.

Conclusion: These results indicate that A. lappa may serve as a promising plant-derived anticancer medication for colon cancer.

Upregulation of TPX2 and KIF20A in colorectal cancer

Fatemeh Ghadiri — 2025-02-28

Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, with metastasis significantly reducing patient survival. Despite advances in treatment, the molecular mechanisms underlying the progression of colorectal cancer remain poorly understood. Recent studies highlight the role of TPX2 and KIF20A, two proteins involved in cell division, in the development of cancer. TPX2 plays a key role in the assembly of the mitotic spindle, while KIF20A is a member of the kinesin superfamily, which is important for intracellular transport and cytokinesis. Both genes are associated with various types of cancer, but their specific contribution to CRC remains unclear. The aim of this study is to investigate the expression and prognostic significance of TPX2 and KIF20A in CRC through bioinformatic analysis and experimental validation.

Methods: To identify differentially expressed genes (DEGs) in CRC, five publicly available microarray datasets (GSE39582, GSE8671, GSE9348, GSE21510, and GSE44076) were analyzed using the Limma package in R. Functional enrichment analysis of DEGs was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A protein-protein interaction (PPI) network was created using STRING and visualized using Cytoscape to identify hub genes. Survival analysis of hub genes was performed using the Gene Expression Profiling Interactive Analysis (GEPIA) tool with TCGA data. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic potential of hub genes. Experimental validation was performed on 50 CRC samples using quantitative real-time PCR (qRT-PCR) to measure the expression of TPX2 and KIF20A.

Results: The integrated analysis identified several DEGs significantly involved in CRC, with TPX2 and KIF20A emerging as key hub genes. GO and KEGG analyses showed that these genes are highly associated with cell cycle regulation and mitotic processes. Survival analysis showed that high TPX2 and KIF20A expression correlates with poorer prognosis in colorectal cancer patients. ROC curve analysis confirmed their potential as diagnostic biomarkers. Experimental validation showed significant upregulation of TPX2 and KIF20A in CRC tissues compared to normal controls, supporting the bioinformatic results. Further mechanistic evidence suggests that TPX2 and KIF20A contribute to colorectal cancer progression by promoting cell proliferation and tumor formation. Previous studies also suggest that KIF20A activates the JAK/STAT3 signaling pathway, thereby increasing the aggressiveness of colorectal cancer cells, while TPX2 is associated with chromosomal instability and tumorigenesis. These results suggest that targeting TPX2 and KIF20A may offer new therapeutic opportunities for the treatment of colorectal cancer.

Conclusion: This study highlights the potential role of TPX2 and KIF20A as prognostic biomarkers and therapeutic targets in colorectal cancer. Their significant upregulation in tumor tissue and strong association with poor survival outcomes underscore their importance in colorectal cancer progression. Future research should focus on elucidating the molecular mechanisms underlying their oncogenic role and exploring targeted therapies aimed at modulating their activity to improve outcomes for colorectal cancer patients.

Melioidosis complicating hemophagocytic lymphohistiocytosis: A rare diagnostic entity in paediatric

Nurjannah Hanim Mohd Yassin — 2025-02-28

Background: Hemophagocytic lymphohistiocytosis is a syndrome characterized by excessive immune activation leading to severe systemic inflammation. It encompasses primary and secondary forms, with the latter often triggered by infections. Paediatric cases of melioidosis complicated by hemophagocytic lymphohistiocytosis are rare and diagnostically challenging.

Case presentation: We report the case of a 7-year-old girl who developed a fever for two months that was unresponsive to antibiotics. She was ultimately diagnosed with melioidosis-associated hemophagocytic lymphohistiocytosis after one month in the ward. She presented with multiorgan involvement, including bicytopenia, severe transaminitis, and neurological symptoms. Prompt initiation of immunoglobulin and steroids led to clinical improvement and resolution of the fever. Diagnostic confirmation relied on meeting HLH-2004 criteria despite limited genetic testing availability.

Conclusion: This case underscores the importance of early recognition and aggressive management in pediatric hemophagocytic lymphohistiocytosis secondary to melioidosis to mitigate potentially fatal outcomes.