Advancements in Life Sciences (E-Journal, University of the Punjab)
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Reciprocal relationship between neurodegeneration-related miRNAs and neurohormones in diabetes mellitus patients: The possible mechanism of high glucose neurotoxicity
Get PDFBackground: Diabetes mellitus (DM) is a metabolic syndrome that causes blood glucose to remain consistently above normal. High glucose concentrations in the neuronal niche can harm neurons permanently. Some DM-related molecular events are found to cause neurological abnormalities and cognitive dysfunctions. Dopamine and oxytocin are important neurohormones that are regulated by miRNAs and could also reorganize neural function-related miRNA networks. Therefore, the purpose of this study was to assess how neurohormones and miRNAs linked to neurodegeneration interact in DM patients.Methods: For this purpose, blood samples related to type 1 (T1DM) and type 2 (T2DM) of diabetes and non-diabetic controls were used to measure hormones (dopamine, oxytocin, and thyroid hormones) by using a specific ELISA kit and circulating miRNAs by RT-PCR method.Results: Data revealed a significant reduction of dopamine and oxytocin in both types of DM, which are accompanied by miR-27a, miR-107, and miR-191 up-regulation. PTEN-induced putative kinase 1 (PINK1) protein expression is primarily inhibited by miR-27a, which leads to dopaminergic cell death and consequently reduces dopamine synthesis and release. We also found a significant decrease in miR-23a and miR-128 levels in DM that may promote dopaminergic cell vulnerability, possibly through attenuation of mitochondrial complex I. Comparing the data related to both types of DM confirmed that miR191 and miR-128 levels in T2DM are higher than in T1DM.Conclusion: It was discovered that miRNAs and neurohormones have a reciprocal interaction that may make them a promising treatment target for DM.Keywords: Diabetes mellitus, Neurodegeneration, miRNAs, Dopamine, Oxytocin, Diabetes related neurotoxicit
Pseudopheochromocytoma in the Conflict Zone of Northwest Syria: A Case Report and Literature Review
Get PDFBackground: Pseudopheochromocytoma is a rare clinical entity characterized by symptoms resembling those of pheochromocytoma, despite the absence of an adrenal medullary tumor. Its diagnosis remains difficult due to overlapping features with various other conditions and the absence of definitive diagnostic markers.Methods: We report the case of a 47-year-old male school teacher who developed pseudopheochromocytoma, likely precipitated by psychological stress associated with prolonged exposure to the war-torn environment of Northwest Syria.Results: The patient presented with repeated episodes of sudden-onset severe hypertension, along with palpitations, excessive sweating, headaches, chest discomfort, and facial flushing. A comprehensive workup ruled out endocrine and structural causes. The psychological burden linked to displacement and chronic instability was believed to be a significant contributing factor. Given the patient’s asthma, beta-blockers were avoided. Management with the calcium channel blocker (Diltiazem) and the antidepressant (Sertraline) resulted in substantial clinical improvement.Conclusion: Pseudopheochromocytoma can closely imitate true pheochromocytoma, making careful evaluation essential. In selected cases, calcium channel blockers combined with antidepressant therapy may offer effective symptom control. More studies are needed to establish standardized treatment strategies for this underrecognized condition.Keywords: Hypertension; Pheochromocytoma; Pseudopheochromocytoma; Syria; Conflic
Identification of Allium cepa compounds as Promising Inhibitors against Lung Cancer: An in-Silico Study
Get PDFBackground: Lung cancer is one of the primary causes of cancer-related deaths, and treatment options for advanced-stage disease remain restricted. Overexpression of the epidermal growth factor receptor (EGFR) has been linked to the development of certain cancers. Double-mutated EGFR is an important oncogenic protein in many lung cancer instances. Allium cepa, a common condiment herb, is known for its medical and pharmacological benefits.Methods: The bioactive compound of A. cepa was obtained from the LOTUS database in ‘sdf’ format, and then converted into ‘pdbqt’ format. The prepared compounds library was screened against the double-mutated EGFR using the insilico tool PyRx 0.8 to determine the binding conformations with the lowest binding energies.Result: Eighteen compounds were found to strongly bind with the EGFR protein and have lower binding energy than the cocrystal ligand, with the top five hits being LTS0258243, LTS0042303, LTS0058192, LTS0104946, and LTS0145270. The Asn842, Asp855, Lys745, Met790, Gln791, Leu792, Met793, Ala743, Leu844, Leu718, Val726, Thr854, and Phe723 residues of EGFR were important in binding to these hit compounds. In addition, these compounds have good drug-like properties.Conclusion: The compounds LTS0258243, LTS0042303, LTS0058192, LTS0104946, and LTS0145270 can be used as EGFR inhibitors to manage lung cancer. However, additional experimental studies are required to validate these compounds as EGFR inhibitors.Keywords: Lung cancer, EGFR, Allium cepa, bioactive compounds, virtual screening
Integrative Transcriptomic Analysis of GSE65194 and GSE45827 Datasets Identifying Consistent Gene Expression Signatures and New putative Target in Breast Cancer
Get PDFBackground: Breast cancer represents a complex molecular disease with high heterogeneity &mortality rates globally. Despite advances in treatment strategies, understanding the underlying transcriptional alterations remains critical for developing effective therapies. This study conducted an integrative analysis of transcriptomic datasets GSE65194 and GSE45827 to identify consistent gene expression signatures and potential therapeutic targets in breast cancer.Methods: Differential gene expression analysis was performed using GEO2R. The datasets were analyzed for upregulated and downregulated genes using stringent criteria (adjusted p-value 1). Statistical validation included volcano plots, MA plots, UMAP visualization, and Pearson correlation analysis. Gene overlaps were assessed through Venn diagram analysis.Results: Analysis revealed 5,554 differentially expressed genes in GSE65194 (4,968 upregulated, 586 downregulated) and 4,757 in GSE45827 (4,683 upregulated, 74 downregulated). The datasets showed remarkable correlation (r = 0.9992) and 82.8% overlap in upregulated genes. Key genes including COL11A1 (log2FC = 7.69), COL10A1 (log2FC = 7.33), and CXCL10 showed consistent upregulation across datasets. UMAP analysis demonstrated clear separation between cancer and normal samples, validating the distinct transcriptional profiles.Conclusion: The strong correlation between datasets and consistent gene expression patterns identify reliable molecular signatures in breast cancer. The identified genes, particularly those involved in extracellular matrix remodeling and immune response, represent potential therapeutic targets and diagnostic biomarkers. These findings provide a robust foundation for developing targeted therapeutic strategies, though further functional validation is essential for clinical translation.Keywords: Gene Expression Omnibus; Microarray; Affymetrix; Breast Cancer; Venn Diagram; Pearson Coefficien
Proposal for reclassifying Tellurirhabdus species within the genus Larkinella
Get PDFBackground: Members of the genera Larkinella and Tellurirhabdus are Gram-negative, aerobic, and consist of menaquinone (MK)-7 as their main isoprenoid quinone. Recent analysis suggests that both genera share similar characteristics. The taxonomic position of the genera Larkinella and Tellurirhabdus has been evaluated using genomic analysis.Methods: The quality of the genomic sequences of Larkinella and Tellurirhabdus was assessed after they were downloaded from NCBI (https://www.ncbi.nlm.nih.gov/). Average nucleotide identity (ANI) and average amino acid identity (AAI) data was used for evaluating their genomic relatedness.Results: The AAI values between Larkinella and Tellurirhabdus were above the threshold value of genus delineation (>60–65 %) indicating that they are members of the same genus. The ANI values among Larkinella and Tellurirhabdus species were below 95-96% indicating they were different species.Conclusion: We propose transferring Tellurirhabdus bombi to the genus Larkinella as Larkinella bombi comb. nov. and Tellurirhabdus rosea to the genus Larkinella as Larkinella roseola nom. nov. based on our research findings.Keywords: Larkinella; Tellurirhabdus; Reclassification; Average amino acid identity; Average nucleotide identit
Targeting BCL-2 in Hematological Cancers: Computational Screening of Cucurbitacins as Promising Inhibitors
Get PDFBackground: Disrupting the balance between cell proliferation and death is critical in cancer formation. Increased resistance to apoptosis, which is frequently caused by BCL-2 overexpression, is a critical oncogenic mechanism in many hematologic malignancies, notably lymphoid neoplasias. Overexpression of anti-apoptotic BCL-2 proteins is frequent in many malignancies, prompting the development of BCL-2 inhibitors as therapeutic agents.Methods: In this study, cucurbitacin compounds were screened against BCL-2 using in silico PyRx tool to find strong natural inhibitors for treating hematological malignancies. ADMET-AI web interface was used to analyze ADMET properties of hit compounds. Results: Cucurbitacin O, IIb, K, and H were effective BCL-2 inhibitors, with binding energies ranging from -8.0 to -8.8 kcal/mol, similar to the control compound (-7.9 kcal/mol). These compounds interacted with key amino acid residues in BCL-2. The radial graphs showed that all four compounds had good ADMET characteristics. The compounds have a high probability of being safe for the blood-brain barrier and pose a low risk of hERG channel blockage. Furthermore, they have higher oral bioavailability and adequate water solubility. Their minimal clinical toxicity profiles indicate their potential safety in therapeutic applications.Conclusion: Cucurbitacin O, IIb, K, and H can be employed as BCL-2 inhibitors to manage hematological malignancies. However, further experimental studies are needed to validate these compounds as BCL-2 inhibitors.Keywords: Cancer; Apoptosis; BCL-2; Cucurbitacin compounds; Drug-likeness
Target-based Virtual Screening of Natural Compounds as Promising Anti-Parkinson’s Agents
Get PDFBackground: Parkinson's disease (PD), the second most common neurodegenerative disease among the elderly, is caused by the death of dopaminergic neurons, resulting in dopamine depletion. Monoamine oxidase B (MAO-B) is an important enzyme in PD because it degrades dopamine. Dopamine levels can be elevated by inhibiting MAO-B, especially in the early stages of the disease.Methods: This study involves virtual screening (docking) of ZINC database natural compounds (N = 200) against MAO-B, followed by ADME and drug-likeness analysis of the top hits.Results: ZINC899884, ZINC4098705, ZINC14764165, and ZINC18847036 compounds exhibited strong binding to MAO-B and interacted with key MAO-B residues. The Cys172, Ile198, Phe168, Ile199, Leu171, Gln206, Gly58, Tyr326, Leu328, Phe343, Tyr398, Ser59, Tyr60, Gly434, and Tyr435 residues of MAO-B were important in binding with these compounds. In addition, these compounds, like the control Rasagiline, interact with MAO-B via several common residues. Furthermore, ADME and drug-like prediction resulted in promising results, indicating that these compounds have a high gastrointestinal absorption property.Conclusion: ZINC899884, ZINC4098705, ZINC14764165, and ZINC18847036 can be used as MAO-B inhibitors for PD. However, experimental validation is required to optimize them as MAO-B inhibitors.Keywords: Drug-likeness; Monoamine oxidase B; Natural compounds; Neurodegenerative disease; Parkinson’s diseas
Analyzing the Possible Impact of Herpes Simplex Virus-1 in Relation to Interleukin-6 Levels in Patients with Oral Squamous Cell Carcinoma
Get PDFBackground: Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity, accounting for more than 90% of all cases. Oral herpes is caused by herpes simplex virus type 1 (HSV-1), a common, benign virus that affects the skin and mucous membranes of individuals with weakened immune systems, causing ulcers. There are several cellular processes that rely on the pleiotropic cytokine interleukin-6 (IL-6), including migration, invasion, differentiation, proliferation, and survival. By modifying tumor angiogenesis and tumor lymphangiogenesis, IL-6 controls tumor growth and its effects on tumor cells.Methods: The study involved 60 patients divided into two groups: those with and those without oral cancer. The blood was drawn and examined for HSV-1 Immunoglobulin G levels using the Herpe Select-1 ELISA kit. A sandwich ELISA was also employed to study IL-6 levels.Results: HSV-1 incidence in these oral squamous cell carcinoma grade groups increased significantly. This research found that the OSCC group had somewhat greater IL-6 levels than the control groups.Conclusion: HSV-1 is not carcinogenic in its own right; however, it is linked to an increased risk of oral squamous cell carcinoma. In addition, the present study discovered that the pro-inflammatory cytokine IL-6 was present in greater quantities in patients' blood than in controls. Interleukin-6 was identified as a potentially hazardous factor in the development of oral cancer and has the potential to function as a valuable biomarker for the assessment of OSCC severity.Keywords: Oral squamous cell carcinoma; Interleukin 6; Enzyme-Linked Immunosorbent Assay; Herpes simplex virus-1; IgG
Production and purification of Nattokinase from Pseudomonas aeruginosa P49
Get PDFBackground: Nattokinase (NK) is a profibrinolytic serine protease enzyme produced by many bacterial strains, such as Pseudomonas aeruginosa. Therefore, this study aimed to produce NK from local isolate of P. aeruginosa P49 and optimize its conditions for the production of enzyme.Methods: 150 samples were obtained from clinical sources, during the period from August to November 2022, from different hospitals. All samples were subjected to different examinations, in addition to VITEK2 system, to confirm that these isolates were P. aeruginosa.Result: A total of one hundred P. aeruginosa isolates were screened to choose the best NK-producing isolates using skim milk agar, then broth media, whereas P. aeruginosa P49 gave the highest enzymatic activity (337.9 U/mg protein). Optimal conditions for the formation of NK were estimated, and the results showed that the maximum production of NK was gained using peptone-yeast medium containing sucrose, peptone, and CaSO4.2H2O at pH 7.5 and 37°C for 24 hours of incubation, whereas the activity of NK increased to reach a yield of 1603 U/mg protein. The NK was purified from P. aeruginosa P49 utilizing ion exchange chromatography (IEC) after precipitation by ammonium sulfate (0-75%). The results for enzyme purification gave 96% of NK enzyme with a purification fold of 3.6, and the specific activity was 2190.7 U/mg protein.Conclusion: This result suggests P. aeruginosa P49 is a good source of NK production.Keywords: Nattokinase; Pseudomonas aeruginosa; Enzyme Purification; IEC; SF; VITEK2 system; Ion exchange Chromatograph
Immunohistochemical expression of Annexin A2 and Annexin A6 in a random sample group of Iraqi women with triple-negative breast cancer
Get PDFBackground: Breast cancer represents the most common and the first leading cause of cancer-associated deaths in Iraqi women. It is a heterogeneous disease with different subtypes; one of these subtypes is triple-negative (basal-like) breast cancer, which is characterized by a distinctive molecular profile, aggressive clinical behavior, and the absence of targeted therapies. Annexin A2 and Annexin A6 are part of the Annexin protein family; these proteins have a suggested role in the evolution and progression of many cancer types, including breast cancer. Evaluation of the immunohistochemical expression of Annexin A2 and Annexin A6 in triple-negative subtype) in a random sample group of Iraqi women patients and correlating the results with clinicopathological parameters, including tumor grade and stage.Methods: The current study was conducted in Baghdad /Iraq, in which forty paraffin-embedded blocks of breast tissue from women patients diagnosed with breast cancer were collected and selected to be triple-negative breast cancer. Immunohistochemical staining of Annexin A2 and Annexin A6 markers was performed for this sample with a correlation of the results with clinicopathological parameters, including tumor grade and stage.Results: The study demonstrates a significant association between Annexin A2 and Annexin A6 expression and a significant association between Annexin A2 expression and tumor grade and stage in triple-negative breast cancer in this group of Iraqi patients.Conclusions: This study displays the role of Annexin A2 and Annexin A6 in triple-negative breast cancer and suggests the role of Annexin A2 in the progression, metastasis, and prognosis of this special type of breast cancer by its association with advanced tumor grade and stage.Keywords: Annexin A2; Annexin A6; triple-negative; Breast cancerEditorial Expression of Concern:18 May 2025: Following publication of this paper, the internal audit (consequent to concerns on quality raised by Web of Science) notified Advancements in Life Sciences about problems in use of references. By this Editorial Expression of Concern, we alert the scientific community as we address the errors.Editorial Note:29 May 2025: You are viewing the latest version of this article having minor corrections in bibliographic section. Expression of concern is hereby revoked