Biochemistry Publications (BUCM-IC)

ROLE OF MICROBIAL INFECTIONS AND BIOCHEMICAL DYSREGULATION IN LEUKEMOGENESIS, DISEASE PROGRESSION, AND DIAGNOSTIC BIOMARKERS: A REVIEW

Thu, 01 Jan 2026 00:00:00 GMT

ROLE OF MICROBIAL INFECTIONS AND BIOCHEMICAL DYSREGULATION IN LEUKEMOGENESIS, DISEASE PROGRESSION, AND DIAGNOSTIC BIOMARKERS: A REVIEW Asma Tariq, Isra Saeed, Dr.Aamnah Sajid, Dr.Humaira Hashmat, Ayesha Kashif, Mudassar Mehmood, Sidra Jabeen, Muhammad Umar Uncontrolled hematopoietic cell growth and poor differentiation are hallmarks of leukemia, a diverse group of hematological cancers. A growing body of research indicates that leukemogenesis, illness progression, and clinical outcomes are significantly influenced by microbial infections and metabolic instability. Through processes like immunological dysregulation, genomic instability, chronic inflammation, and direct oncogenic transformation, a number of viruses, bacteria, and parasites have been linked to the development and spread of leukemia. Certain leukemia subtypes are closely linked to viral agents such as hepatitis viruses, Epstein-Barr virus (EBV), and human T-cell leukemia virus type-1 (HTLV-1), while bacterial and parasitic infections may indirectly contribute by causing oxidative stress and prolonged inflammatory reactions. Leukemic cell survival and proliferation are largely dependent on biochemical changes, including aberrant expression of enzymes and cellular metabolites, oxidative stress imbalance, altered cytokine signaling, and metabolic reprogramming. These metabolic alterations offer useful indicators for prognosis and diagnosis in addition to influencing the course of the disease and treatment resistance. Changes in immunological mediators, metabolic intermediates, inflammatory markers, and serum enzymes have demonstrated potential value in risk assessment, early diagnosis, and treatment response monitoring. The current understanding of the involvement of metabolic abnormalities and microbial infections in the development and course of leukemia is compiled in this study. 1Asma Tariq, 2Isra Saeed, 3Dr.Aamnah Sajid, 4Dr.Humaira Hashmat, 5Ayesha Kashif, 6Mudassar Mehmood, 7*Sidra Jabeen, 8Muhammad Umar 228 1. Introduction The unchecked growth and accumulation of aberrant hematopoietic cells in the bone marrow, peripheral blood, and occasionally extramedullary tissues is the hallmark of leukemia, a diverse collection of malignant illnesses. The main subtypes are acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and chronic lymphocytic leukemia. It is typically categorized based on the affected cell lineage (myeloid or lymphoid) and disease progression rate (acute or chronic) (Short et al., 2021). Leukemia causes severe morbidity and mortality in all age categories, making it a major global health burden.Leukemia accounts for a significant fraction of cancer incidence and fatalities globally, with notable geographic and demographic variations caused by environmental, genetic, and socioeconomic factors, according to latest global cancer estimates (Sung et al., 2021). Leukemia's biological heterogeneity, recurrent relapse, and drug resistance make it difficult to treat despite advancements in molecular diagnostics and targeted medicines. This emphasizes the significance of understanding the disease's etiological and pathogenic pathways. Improving prevention, early detection, and treatment outcomes requires an understanding of the pathogenic and etiological elements underlying leukemia. It is currently understood that leukemogenesis is a multistep process that disrupts normal hematopoiesis through immunological dysregulation, genetic abnormalities, epigenetic changes, and environmental exposures (Greaves, 2022). Even though somatic genetic changes are essential to malignant transformation, they frequently need cooperating internal or external stimuli to start or spread illness. A growing body of research indicates that host biochemical disorders and pathogenic pathogens may function as such cofactors, causing altered immune surveillance, persistent inflammation, and genomic instability. Particularly in people with underlying genetic predisposition, these mechanisms can foster the emergence and growth of malignant clones. Both epidemiological and mechanistic evidence support the focus on microbial infections as probable causes of leukemia. Human T-cell leukemia virus type 1, which is causally linked to adult T-cell leukemia/lymphoma, is one example of an oncogenic virus that has been directly linked to certain hematological malignancies (Cook et al., 2021). Other viral infections, such as Epstein-Barr virus, cytomegalovirus, and hepatitis viruses, may affect leukemia risk, disease progression, or treatment response through indirect mechanisms like immune modulation and chronic inflammatory signaling, according to recent research, which goes beyond established associations (de Martel et al., 2020). In the bone marrow microenvironment, persistent infections may promote leukemic transformation or clonal development by causing prolonged cytokine release, elevated oxidative stress, and compromised immune control. Additionally, it emphasizes the use of new laboratory biomarkers derived from biochemical and viral pathways for diagnosis, prognosis, and individualized illness therapy. The development of more effective leukemia prevention techniques, focused treatments, and sophisticated diagnostic instruments may be aided by an understanding of these interconnected pathways. Assistant Professor Dr Aamnah Sajid, Biochemistry BUCM

Role Of IL-6, Αtnf And Calprotectin In Acpas Positive & Negative Patients Of Rheumatoid Arthritis

Wed, 01 Jan 2025 00:00:00 GMT

Role Of IL-6, Αtnf And Calprotectin In Acpas Positive & Negative Patients Of Rheumatoid Arthritis Humaira Kashif, Farhat Bano, Aymen Shahzad, Rehana Mushtaq Auto immune disease such as Rheumatoid Arthritis is the consequence of persistence imbalance between proinflammatory cytokines and anti-inflammatory immune mechanisms leading to chronic inflammation. In RA, many factors activate multiple pathways, all converging to enhance osteoclastogenesis, ultimately disturbing bone metabolism to bring about joint destruction. This study is aimed at finding levels of serum calprotectin, serum IL-6 and serum TNF-α in treatment naïve seropositive and seronegative RA patients. It also aimed at finding association of these parameters with RA disease in Pakistani population. Subjects and Methods A comparative cross-sectional study was carried out at RA patients of age 35-55 years, not yet started any treatment, divided into group 1 ACPA +ve (n=28) Group 2 ACPA -ve (n=28) and Group 3 healthy control (n=28). Blood samples were taken and processed for serum preparation and stored at -80˚C. The anthropometric profile (height, weight and body mass index) was recorded. ESR, CRP and serological record were taken from medical file of patient. Calprotectin, IL-6 and TNF-α were estimated by human ELISA kits. Data was analyzed by SPSS-21. Normality was checked and statistical tests were applied accordingly. A p value of < 0.05 was considered significant. Results Level of Serum calprotectin, IL-6 and TNF-α were significantly elevated in both ACPA +ve and ACPA -ve RA patients as compared to healthy controls (p value < 0.001), (p value < 0.001), (p value < 0.001) respectively. However, no significant difference in levels of calprotectin, IL-6 and TNF-α was noticed in ACPA +ve and ACPA -ve groups (p value < 0.179), (p value < 0.725), (p value < 0.629) respectively. A notable association of these parameters with DAS-28-ESR was also found. Both seropositive and seronegative groups of our study reported high DAS -28. Conclusion This study found that levels of serum calprotectin, IL-6 and TNF-α were significantly elevated in RA patients as compared to healthy controls and these high levels were associated with RA disease activity. These findings suggest their possible role in disease pathology and these parameters show notable association with disease severity. Moreover, the study concluded that, severity of disease is equally high in both seropositive and seronegative RA patients. Hence, seronegative RA patients cannot be ignored and should be treated promptly. Also, the study concluded that calprotectin has discriminatory capacity to predict disease activity in both groups equally. Assistant Professor Dr Humaira Kashif, Biochemistry BUCM

Mutational Analysis of Peroxisome Proliferator Activated Receptor Alpha (PPARα) Genes and Their Relationship with Lipid Profile in Diabetic Dyslipidemia Patient

Wed, 01 Jan 2025 00:00:00 GMT

Mutational Analysis of Peroxisome Proliferator Activated Receptor Alpha (PPARα) Genes and Their Relationship with Lipid Profile in Diabetic Dyslipidemia Patient Hajira Siddique, Aneela Shabbir; Maryam Wahid Objective: To explore the genetic variants of exon 5 of peroxisome proliferator activated receptors alpha (PPARα) genes in diabetic patients with and without dyslipidemia and healthy controls to define its genetic contribution to development of diabetic dyslipidemia and its relationship with serum lipid profile. Material and Methods: This was a cross-sectional study conducted in MDL of Army medical college from Jan 2021 to Jan 2022. A total of 90 participants were categorized into 3 groups having 30 members each. Group I, diabetic patients having dyslipidemia, group II. diabetic patients without dyslipidemia and group III of healthy controls. DNA template obtained from blood was amplified by PCR. After purification and sequencing PCR, sequencing was performed and analysis done by BIOEDIT software. Demographic along with clinical data was also collected and analyzed by SPSS version 22. Results: No significant mutation was found in the concerned exon of PPARα gene during the study in all three groups. Mean HDL-c (high density lipoprotein) was found to be significantly lower than that of controls. Mean total cholesterol, triglyceride (TG) and serum LDL-c values of group 1 & 2 were found significantly elevated than that of controls. Conclusion: Absence of any variant of this exon in our study suggests the involvement of other exons of PPARα gene to be the causative factors for the development of disorders in metabolic pathways. The levels of total cholesterol, TG, LDL-c and HDL-C are perturbed significantly among diabetic dyslipidemic patients as compared to diabetic non-dyslipidemic patients and normal healthy controls. Senior Professor Dr Maryam Wahid Biochemistry BUCM

Infectious Causes of Acute Meningoencephalitis Syndrome in Children: Insights from a Tertiary Care Hospital in Pakistan

Wed, 01 Jan 2025 00:00:00 GMT

Infectious Causes of Acute Meningoencephalitis Syndrome in Children: Insights from a Tertiary Care Hospital in Pakistan Shakeel Ahmad, Saddam Hussain, Sayed Ali, Waqar Ali Shah, Asad Riaz, Sherziyan Aftab Qazi, Khayyam Haider, Amna Hussain, Muhammad Ahmed, Muhammad Ali Hassan, Basharat Ullah, Avijeet Debnath, Furqan Ul Haq Background: Acute Meningoencephalitis Syndrome (AMES) remains a significant cause of morbidity and mortality in children worldwide, with diverse infectious etiologies varying by geography and resource availability. While vaccines have successfully reduced bacterial meningitis due to Streptococcus pneumoniae and Haemophilus influenzae type B (Hib) in developed regions, serotype replacement and antimicrobial resistance pose ongoing challenges. Objective: This study aimed to determine the frequency of infectious causes of AMES among children presenting to a tertiary care hospital in Khyber Pakhtunkhwa, Pakistan, providing essential epidemiological insights to guide diagnostic and preventive strategies. Methods: A cross-sectional study was conducted in the tertiary care hospital, Peshawar, from August 1, 2023, to January 31, 2024. 130 children aged 1–10 years with acute meningoencephalitis syndrome of ≤72 hours’ duration were enrolled. Lumbar puncture was performed for cerebrospinal fluid (CSF) analysis, and pathogens including Streptococcus pneumoniae, enterovirus, herpesvirus VI, Mycobacterium tuberculosis, Escherichia coli, and Group B Streptococcus were identified. Data were analyzed using Statistical Package for the Social Sciences version 23, with stratification by age, gender, and duration of symptoms. Results and conclusion: The most commonly identified pathogen was enterovirus (23.1%), followed by Group B Streptococcus (19.2%), Escherichia coli (17.7%), and Streptococcus pneumoniae (16.9%). Herpesvirus VI was detected in 12.3% of cases, while Mycobacterium tuberculosis was the least frequent (3.8%). Male patients accounted for 73.1% of cases. Age stratification indicated higher infection rates among younger children (1–5 years), although no statistically significant differences were observed across age groups, gender, or symptom duration. Viral etiologies, particularly enteroviruses, remain the predominant cause of pediatric AMES, aligning with global trends. However, the considerable burden of bacterial infections underscores the continued need for improved vaccination coverage and antimicrobial stewardship. The low detection rate of Mycobacterium tuberculosis likely reflects diagnostic limitations rather than its true prevalence. These findings highlight the importance of early diagnosis, targeted treatment strategies, and enhanced surveillance to improve outcomes in pediatric acute meningoencephalitis syndrome cases. Lecturer Dr Basharat Ullah, Biochemistry BUCM