INTRODUCTION: Remifentanil, a fentanyl-derivative opioid analgesic acting as a μ-opioid receptor agonist, is a crucial drug in anesthesia due to its numerous benefits during surgical procedures. This study aimed to explore whether remifentanil effectively induced apoptosis in MCF-7 breast cancer cells via possible mechanisms.
METHODS: Flow cytometry was performed for Annexin V/7-aminoactinomycin (7-AAD) and DAPI staining, cell cycle assays, and to measure reactive oxygen species (ROS) levels. Immunoassays for lactate dehydrogenase (LDH) and interleukin (IL)-6, as well as a chorioallantoic membrane (CAM) test, were also performed.
RESULTS: Remifentanil effectively suppressed cell proliferation and led to the induction of cell cycle arrest at the G1 phase in MCF-7 cells. Compared with the control group, MCF-7 cells treated with remifentanil had a higher apoptotic rate with nuclear fragmentation, increased LDH release, and lower IL-6 concentrations. Overgeneration of ROS and decreased angiogenic activity were also observed in remifentanil-treated MCF-7 cells.
DISCUSSION AND CONCLUSION: Remifentanil led to G1-phase arrest and apoptosis in MCF-7 cells. The mechanism of action of remifentanil likely involves the suppression of IL-6 production and angiogenesis, along with enhanced ROS levels and LDH generation. This preliminary study highlighted the need for further experimental evidence from future research to clearly support the significant potential of remifentanil as an anticancer agent for breast cancer.

INTRODUCTION: A sedentary lifestyle can be defined as spending most of your time without physical activity, such as sitting or lying down for long periods during the day. This lifestyle is considered the least energy-consuming state in the
body, which means accumulating a lot of calories in the body. Collagen type 1 C-telopeptide (CTX-1) is the C-terminal telopeptide of fibrillar collagens, such as collagen type I, and has an important role in stabilizing protein tertiary and quaternary structures for bone tissues. It is usually used as a biomarker in serum samples to assess the bone turnover rate. Thyroid-stimulating hormone (TSH) is a peptide hormone secreted by the pituitary gland in the brain. TSH is responsible for sending a signal to the thyroid gland to increase or decrease the amount of hormones it secretes. This study aims to show the correlation between CTX-1 and TSH in individuals who have a sedentary lifestyle, which in turn causes osteoporosis in those individuals. This shows the harms of sedentary lifestyle conditions on individuals.
METHODS: The study was designed based on selecting two groups of male individuals (the first group: 25 individuals living a sedentary lifestyle, and the second group: 25 individuals who have physical activity regularly). Blood samples were collected from all individuals in the study after obtaining their consent. The blood samples of the individuals were used to measure several parameters, including CTX-1, TSH, T4, and T3. The t-test statistical method was used to determine the clinically important values.
RESULTS: The results of the study, after comparing the individuals of the sedentary lifestyle group and the active lifestyle group by the t-test statistical method, showed the following: A significant increase in the level of CTX-1 in the
individuals of the Sedentary Lifestyle Group. A significant decrease in the levels of T3, T4, and TSH in the individuals of the Sedentary Lifestyle Group. The presence of an inverse or negative correlation between CTX-1 and TSH in the individuals of theSedentary Lifestyle Group.
DISCUSSION AND CONCLUSION: The results of this study concluded the importance of physical activity for the body, as the study showed that a sedentary lifestyle causes several disorders, including secondary hypothyroidism, which in turn can cause osteoporosis in individuals.

INTRODUCTION: Anemia, a widespread public health concern, affects millions globally, particularly in developing countries.
Traditional medicinal plants, including Mucuna pruriens and Justicia carnea, have been used to manage anemia due to their potential hematopoietic and antioxidant properties. This study investigated the hematological effects of Mucuna pruriens, Justicia carnea, and their combination on phenylhydrazine-induced anemia in rats, aiming to provide insight into their therapeutic potential.
METHODS: The acute oral toxicity test (LD50) was conducted using the Up-and-Down procedure. Anemia was induced
in all rats, excluding the normal control group, via a single-dose intraperitoneal injection of 80 mg/kg phenylhydrazine. Thirty (30) adult male albino rats were assigned into six (6) groups of five (5) rats, consisting of the normal control, anemic control, and treated groups (standard drug—Astyfer 1.5 mg/kg, 200 mg/kg of ethanol leaf extracts of Mucuna pruriens, Justicia carnea, and their combined leaf extracts). Treatment was given orally once per day and lasted for 21 days. Blood samples were collected two weeks into treatment and three weeks after treatment. Hematological parameters were determined using standard biochemical methods. The parameters analyzed were hemoglobin (HB), packed cell volume (PCV), and red blood cell count (RBC).
RESULTS: The LD50 results revealed no mortality or signs of toxicity at doses up to 5000 mg/kg body weight. The findings of this study revealed that, two weeks into treatment, all treatment groups showed a significant increase (p<0.05)
in their HB, PCV, and RBC levels compared with the anemic control. At the end of the treatment (three weeks), the HB of groups treated with 200 mg/kg Justicia carnea and the combined extract were significantly higher (p<0.05) than in the other groups.
DISCUSSION AND CONCLUSION: The combination of Mucuna pruriens and Justicia carnea offered a modest additional benefit, although the
improvement was not substantially greater than the individual effects of each extract.

INTRODUCTION: Human skin, the largest organ, serves as a critical barrier against environmental damage and microbial
invasion. The skin aging process leads to collagen degradation, reduced elasticity, and wrinkle formation, influenced by intrinsic and extrinsic factors. This process has driven significant interest in the anti-aging market, which is expected to grow to $44.5 billion by 2030. Asiaticoside (AS) has exhibited anti-aging properties by promoting collagen synthesis and fibroblast proliferation.
METHODS: This study employed bioinformatics analyses to identify molecular targets and pathways modulated by AS
in skin aging. The gene databases were extracted from PubMed (www.ncbi.nlm.nih.gov), OMIM (www.omim.org), and GeneCards (www.genecards.org). Protein-protein interaction (PPI) networks and CytoHubba algorithms (MCC, DMNC, MNC) identified ten key genes implicated in the skin aging cascade. To validate the results, molecular docking was conducted to assess AS's binding affinity to these targets.
RESULTS: This study identified IL-1β, JUN, TGF-β1, CCL-2, MMP-9, STAT-3, MAPK-3, CXCL-8, MMP-2, and KDR as potentially targeted by AS in the skin aging cascade. Molecular docking revealed a strong binding affinity of AS with MMP-9 (-8.16 kcal/mol), indicating its role in inhibiting ECM degradation.
DISCUSSION AND CONCLUSION: This study highlights AS's potential as a promising anti-aging agent by targeting key proteins and pathways, paving the way for further therapeutic exploration. This prediction of molecular pathways should be further
verified by in vitro and in vivo experiments.

INTRODUCTION: Hyperglycemia, one of the most important metabolic indicators of diabetes, causes increased oxidative stress and inflammation both systemically and locally at the tissue level, particularly in chronic wound sites where healing is impaired. Increased oxidative stress products are controlled by the body's antioxidant capacity. Oxidative damage develops as a result of excessive production or improper quenching of reactive oxygen species (ROS) and is an important cause of non-healing chronic wounds. We aimed to accelerate wound healing by increasing the antioxidant capacity of oxidative damage caused by diabetes by applying metformin, which is routinely used orally, topically on wounds.
METHODS: For this purpose, we applied metformin on diabetic and non-diabetic wounds for 14 days and measured oxidative stress markers malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS) levels, and antioxidant levels of glutathione (GSH) and catalase (CAT) in wound samples obtained by biopsy using ELISA technique.
RESULTS: The markers of oxidative stress increased in untreated diabetic rats because of hyperglycemia, the most important clinical marker of diabetes, compared to non-diabetic rats. In contrast, our results showed that metformin administration decreased oxidative stress markers and increased antioxidant levels compared to controls.
DISCUSSION AND CONCLUSION: As a result, it has been revealed that topically applied metformin can minimize oxidative damage caused by hyperglycemia by increasing antioxidant capacity, especially in diabetic wounds, and thus wounds heal faster by
controlling oxidative stress in wound healing.

INTRODUCTION: Recurrent spontaneous abortion (RSA) is the successive loss of pregnancy experienced by 1-2% of women
with clinically recognized pregnancies. The role of cytokines and their regulators in RSA has gained significant attention in recent years. The GATA3 transcription factor has significant implications for maternal-foetal health outcome by modulating the immune T-cell population to T helper cell subsets that produce the proinflammatory (IFNγ) and anti-inflammatory cytokines (IL4) required for pregnancy maintenance.
METHODS: The study involved 65 case-women with RSA and 70 control-women without a history of RSA. IL-4, IFNγ, and
GATA3 transcription factor levels were analysed in maternal serum and placental tissues. Correlation analysis was performed for GATA3 expression and cytokine levels, and the results were tested for statistical significance
RESULTS: The mRNA expression of the GATA3 transcription factor was significantly reduced in both the maternal blood and placental tissues of the RSA group compared to the control group undergoing medical termination (p≤0.05*). Additionally, compared to the control group, the levels of the Th1 cytokine IFN-γ were significantly elevated (11034 pg/ml & 87.4735 pg/g), while the levels of the Th2 cytokine IL4 were significantly decreased (48.9832 pg/ml & 6320 pg/g) in RSA mother and their placenta samples respectively. Moreover, cytokine levels in the RSA group showed a significant correlation with GATA3 expression.
DISCUSSION AND CONCLUSION: The study suggests that altered GATA3 levels and an increased IFN-γ/IL-4 ratio may increase the risk of recurrent spontaneous abortions in Telangana women.

INTRODUCTION: The effect of infertility does not exert a futuristic effect on society only but puts emotional and psychological stress on couples no matter who may show this problem. Thus, searching for obvious and hidden reasons to treat this problem took significant leaps to overcome it and provide couples with means of treatment. This article aims to investigate the role of specific microRNAs (miRNAs) as miR-429 and miR-425 and pro-inflammatory cytokines as interleukin-1 alpha (IL-1α) and tumor necrosis factor-alpha (TNF-α) on male fertility.
METHODS: 100 semen samples were collected from healthy men with offspring and another 100 samples were collected from men suffering from fertility impairment for Semin fluid analysis (SFA). Cytokines levels in the serum were
measured using sandwich ELISA technique, whereas DNA samples were obtained from both categories of participants from blood.
RESULTS: Results showed that infertile patients showed high level of both tumor necrosis factor (TNF-α) and interleukin
(IL-1A) which affected semen quality, motility, and to fertilize mature oocytes. In addition, high levels of miRNA 425, and 429 were detected in patients compared to control. We found specific type of single nucleotide polymorphism (SNPs) that reduced the ΔG in miRNAs within patients giving them the chance to be circulated for longer half time than the control which modified the RNA decay mechanism.
DISCUSSION AND CONCLUSION: Immunological and epigenetic factors can play a crucial role in infertility manifestation in male. Since immunological factors are widely studied and been taken in concern in fertility clinics, epigenetic factors may be the key to overcome such clinical case and need to take in concern to provide a proper medical care.

INTRODUCTION: This study aimed to investigate serum Maresin-1 (MaR1) levels among obese, overweight, and normal-weight groups, as well as to evaluate their association with various metabolic parameters, including insulin resistance-related indices and lipid profiles.
METHODS: Ninety subjects were classified into three distinct groups in terms of body mass index (BMI). Using a median MaR1 value of 608 pg/mL as the threshold, the participants were also categorized into two distinct groups. Serum MaR1 levels were quantified via an ELISA. The study also evaluated several other indicators: metabolic score for insulin resistance (METS-IR), triglyceride glucose-body mass index (TyG-BMI), HbA1c, and various components of the lipid profile.
RESULTS: MaR1 levels were significantly lower in the obese and overweight categories compared to the normal-weight categories. Nevertheless, no statistically significant difference was observed in the MaR1 levels between the obese and overweight groups. MaR1 levels were negatively linked to METS-IR (r=-0.444, p<0.001) and TyG-BMI (r=-0.427, p<0.001), whereas quantitative insulin sensitivity check index (r=0.318, p=0.002) levels were positively correlated. METS-IR had the highest AUC value (0.706), with 73.3% sensitivity and 57.8% specificity to identify high levels of MaR1 (p<0.001).
DISCUSSION AND CONCLUSION: Ordinal logistic regression revealed a significant independent relationship between MaR1 levels and BMI categories. The close association between MaR1 and metabolic indices such as METS-IR and TyG-BMI suggests its role in insulin sensitivity and obesity-associated metabolic disorders.

INTRODUCTION: Appropriate testing is a part of good laboratory practices. “Requesting the right test with the right method, at the right time, to the right patient, to produce the right result at the right cost” has been defined as an appropriate test request. This study was intended to measure the impact of an attend to regulate requests for serum protein electrophoresis tests before and after applying rejection rules and clinical management.
METHODS: In a meeting in December 2022, hematologists declared to be more careful about proper testing in electrophoresis. In addition, the laboratory was decided to be involved in test request management through test rejection rules. Multiple myeloma patients with measurable M protein spikes in the gamma regions of serum protein electrophoresis tests were chosen due to relatively well-defined follow-up protocols. Number of hospital visits of the patients and electrophoresis test requests were compared with the year before (2022) and the year after (2023) the meeting.
RESULTS: Selected 92 patients visited our hospital 493 times in 2022 and 583 times in 2023 (number of visits). A total of 423 serum protein electrophoresis (SPE) and 416 serum immunofixation electrophoresis (SIFE) tests were requested in 2022 while 427 SPE and 470 SIFE tests were requested in 2023. In 2023, 51 SPE and 36 SIFE test requests were rejected according to the defined test rejection rules.
DISCUSSION AND CONCLUSION: From 2022 to 2023 total patient visits increased by 18%, while SPE test requests increased by less than 1% and SIFE test requests increased by 13%. The common will by the Hematology Clinic and the Clinical Biochemistry Laboratory to reduce unnecessary electrophoresis test requests achieved their goal as the rise in test requests were under the rise in hospital visits. After a year of experience, we could confidently propose that our test rejection rules can be adopted by laboratories and used for electrophoresis test management.

INTRODUCTION: There are insufficient studies on the combined effect of neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation (SII) index and monocyte-to-high-density lipoprotein ratio (MHR) on plaque status and risk of cardiovascular disease (CVD) occurrence. The aim of this study was to demonstrate the feasibility of using NLR, SII index and MHR, which are preferable markers in terms of favorable cost/benefit ratio and easy measurement, to monitor and evaluate the severity of the disease, considering that CVD is an inflammatory disease.
METHODS: Two thousand two hundred seventy-three patients presenting with complaints of shortness of breath or chest pain who were followed up in the Cardiovascular Surgery outpatient clinic of Gaziosmanpaþa Training and Research Hospital between January 2024 and October 2024 were retrospectively included in the study.
RESULTS: Lymphocyte levels were significantly higher in the deceased patients (p=0.02). Conversely, the NLR and the SII were higher in the surviving patients compared to the deceased patients (p<0.001; p<0.001). LDL levels and plaque status were statistically significantly different between the groups. Patients in the moderate-risk group had significantly lower LDL levels compared to those in the mild-risk group (p<0.001).
DISCUSSION AND CONCLUSION: These results suggest that MHR, a novel biomarker derived from the inflammatory marker monocyte and the antiatherogenic HDL, may be associated with CAD. Given that CVD is an inflammatory disease, NLR, SII and MHR may be preferable in terms of favorable cost/benefit ratio and easy measurement. These markers can also be calculated practically and inexpensively from whole blood and HDL values, which are routine tests that can be performed in primary health care centers. It also demonstrates NLR and MHR are associated with plaque formation in patients with atherosclerotic heart disease.

Branched-chain amino acids (BCAAs), such as leucine, isoleucine, and valine, are vital in metabolic processes and in regulating energy equilibrium. In obesity and diabetes, BCAAs have been implicated in various metabolic dysfunctions, such as insulin resistance and altered glucose metabolism. Elevated BCAA levels are often observed in individuals with these conditions, suggesting a potential link between BCAA metabolism and the etiology of obesity and diabetes. Understanding the implications of BCAAs in these disorders could provide insights into novel therapeutic strategies to improve metabolic health and manage these chronic diseases. Previous reviews on BCAAs in the context of obesity and diabetes have often lacked a comprehensive analysis of their dual role in metabolic pathways. These reviews have focused solely on their positive effects, such as muscle protein synthesis, or potential negative impacts, like insulin resistance. Considering recent research findings and clinical studies, a thorough evaluation of the nuanced effects of BCAAs is necessary. This review seeks to fill these gaps by offering an impartial viewpoint on the metabolic onsequences of BCAAs in individuals with obesity and diabetes, highlighting areas for future research and covering the metabolic role of BCAAs, their impact on feed intake patterns, and biochemical insights into BCAA metabolism. The review also delves into leucine's role in diabetes, examining its therapeutic potential and clinical implications. It also investigates mechanisms linking BCAAs to insulin resistance and BCAAs' relationship to mitochondrial dysfunction in obesity, providing a comprehensive understanding of BCAAs' metabolic effects. Given the rising prevalence of obesity and diabetes, this review is crucial for informing therapeutic strategies and identifying areas for future research.