Biochemistry and Biophysics Reports最新文献

{"title":"Alkaline phosphatase–streptavidin conjugate (APSA) enzyme and binding activity over time and storage conditions","authors":"Nan Cheng,&nbsp;Lloyd Johnson,&nbsp;Jaimie Dufresne,&nbsp;Sina Mazinani,&nbsp;John G. Marshall","doi":"10.1016/j.bbrep.2025.102160","DOIUrl":"10.1016/j.bbrep.2025.102160","url":null,"abstract":"<div><div>Alkaline phosphatase (AP) linked to streptavidin (SA) in the form of the APSA enzyme conjugate is required for diagnostic screening for a variety of clinical conditions world wide. The enzyme activity of APSA conjugates in the liquid phase showed variation across samples that declined with storage time. Random sampling of the enzyme activity in the liquid phase (ANOVA p &lt; 2E-16; Regression p &lt; 0.043) and the binding plus enzyme activity of APSA in the model assay (R² &gt; 0.99) of biotinylated human IgG (B-h-IgG) directly adsorbed to 96 well plates showed a similar loss of function over time (ANOVA p &lt; 9.15E-15, Regression p &lt;1.1E-9). The enzyme AP showed little dissociation from the SA moiety while proteolysis of the BSA carrier was observed. Covalent protease inhibitors 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) or tosyl-<span>l</span>-lysine chloromethyl ketone hydrochloride (TLCK) abrogated AP enzyme activity, but the competitive inhibitors epsilon-aminocaproic acid (EACA) and benzamidine (BNZ) had no protective effect on APSA activity over time. Samples of APSA showed large variation in enzyme activity (p ≤ 2E-16) and so were titrated by the colorimetric assay and standardized against indigo blue in DMSO to achieve an initial OD value of ∼1.0 at 595 nm prior to following activity over storage time. After titration, the effect of temperature, addition of glycerol prior to freezing, and freeze drying with or without trehalose and sucrose, on alkaline phosphatase activity was compared using a sampling schedule over storage time. The alkaline phosphate activity was not immediately sensitive to freeze-drying but was sensitive to storage time and ultra-low temperatures, but the addition of sugars or glycerol to the APSA prevented some of the activity loss. Storage of APSA on wet ice or in 50 % glycerol at −20 °C retained about 50 % of the starting optical density reading of APSA after 170 days in storage.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102160"},"PeriodicalIF":2.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and optimization of a guanylhydrazone-based small molecule to replace bFGF for cell culture applications","authors":"Mikhail Feofanov ,&nbsp;Gerrit Martin Daubner ,&nbsp;Andrea Saltalamacchia,&nbsp;Karsten Köhler,&nbsp;Christine Schulz,&nbsp;Clare Elizabeth Henry,&nbsp;Michael Josef Ziegler,&nbsp;Mohammed Benabderrahmane,&nbsp;Florence Andrée Hiault,&nbsp;Tim-Michael Decker,&nbsp;Mei-Chun Shen,&nbsp;Jürgen Pahl,&nbsp;Sophie Lambertz,&nbsp;Hamid R. Noori","doi":"10.1016/j.bbrep.2025.102167","DOIUrl":"10.1016/j.bbrep.2025.102167","url":null,"abstract":"<div><div>Replacing growth factors with a synthetic alternative molecule is an attractive opportunity to increase consistency, scalability, and cost-effectiveness of cell-based products. Herein, we describe the discovery of a chemical class of FGFR1 agonists that mimic the action of basic fibroblast growth factor (bFGF), an essential component of cell culture media. The guanylhydrazone-based molecule, TCB-32, was identified via structure-based virtual screening of the orthosteric binding site of FGFR1. It was shown to significantly increase cell proliferation by activating the FGFR1 signaling pathway like bFGF and exhibited enhanced thermostability over bFGF by retaining activity over the course of several days. After extensive structure-activity relationship studies, it was possible to increase potency and efficacy leading to three highly potent agonists. This finding has the potential to remove current bottlenecks in large-scale cell production, as required for applications such as cultivated meat or cell therapy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102167"},"PeriodicalIF":2.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genetic puzzle of rheumatoid arthritis: Causes, progression, and treatment","authors":"Maryam Masoumi ,&nbsp;Mahdi Solaymani ,&nbsp;Mitra Abbasifard ,&nbsp;Sheyda Houshmandfar ,&nbsp;Parnia Iravani ,&nbsp;Ali Saeedi-Boroujeni ,&nbsp;Jafar Karami","doi":"10.1016/j.bbrep.2025.102148","DOIUrl":"10.1016/j.bbrep.2025.102148","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a multifaceted autoimmune disorder characterized by chronic inflammation and progressive joint destruction, influenced by a complex interplay of genetic and environmental factors. Substantial evidence highlights a significant genetic contribution to RA pathogenesis, with key genetic risk factors including human leukocyte antigen (HLA) genes and non-HLA variants. These genetic elements are intricately involved in immune dysregulation, antigen presentation, and signaling pathways. The genetic heterogeneity of RA is further accentuated by gene-gene and gene-environment interactions, while biomarkers and genetic profiles associated with disease progression and joint damage continue to be rigorously explored. Additionally, the evolving field of pharmacogenomics sheds light on the challenges and prospects of developing personalized therapeutic approaches for RA. Genetic markers are being explored to predict response to various RA therapies, including DMARDs and biologics. Understanding genetic risk factors and pharmacogenomic insights can support early diagnosis, predict disease severity and progression, and improve therapeutic decisions in RA patients. The main objective of this review is to comprehensively explore current knowledge regarding the genetic factors contributing to RA susceptibility, progression, and treatment response. Furthermore, by addressing genetic risk factors, gene-environment interactions, and emerging pharmacogenomic insights, the review aims to highlight critical gaps and future directions in genetic researches related to RA.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102148"},"PeriodicalIF":2.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DODAB-ODN lipoplex structure is highly dependent on ODN concentration: A multitechnique experimental study","authors":"Cristofher Victor Vivas ,&nbsp;Antonio R. da Cunha ,&nbsp;M. Teresa Lamy ,&nbsp;Evandro L. Duarte ,&nbsp;Gabriel S. Vignoli Muniz","doi":"10.1016/j.bbrep.2025.102128","DOIUrl":"10.1016/j.bbrep.2025.102128","url":null,"abstract":"<div><div>This study explores the structural properties of lipid vesicles composed of dioctadecyldimethylammonium bromide (DODAB) and varying concentrations of the oligonucleotide 5′-AAAAAAAAAA-3’ (ODN). The vesicles, in both gel and fluid phases, were characterized using dynamic light scattering (DLS), Zeta potential, small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and fluorescence with the fluorescent probe Laurdan embedded into DODAB vesicles. The DODAB-ODN interaction induces concentration-dependent structural changes on the lipoplex. At relatively low ODN concentrations ([ODN]/[DODAB] &lt; 0.050), the dispersion remains stable, with positively charged vesicles, though with an increase in vesicle size and sample turbidity, and SAXS indicates coalescence of vesicles with multilamellar structure formation. DSC revealed the coexistence of ODN-free and ODN-rich regions, with the latter showing increased thermal stability. Laurdan fluorescence indicates that the probe does not significantly partition into the lipoplex ODN-rich regions. At intermediate concentrations (0.050 &lt; [ODN]/[DODAB] &lt; 0.075), colloidal stability is lost, and pure DODAB domains are no longer detected. At relatively high ODN concentrations (0.075 ≤ [ODN]/[DODAB] ≤ 0.200), the dispersion is stable, showing a negative vesicle surface potential, and the presence of small multilamellar vesicles. Laurdan lifetimes are significantly increased, suggesting that ODN induces lipid packing or dehydration at the surface of the vesicles in both the gel and fluid phases. These findings enhance our understanding of the structure of lipid-ODN aggregates, paving the way for their application in gene therapy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102128"},"PeriodicalIF":2.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential of efferocytosis for the treatment of bronchial asthma: A review of current trends, mechanisms and prospects","authors":"Baohe Liu ,&nbsp;Tingting Zu ,&nbsp;Yaqi Lu ,&nbsp;Chaopin Xing ,&nbsp;Meng Gao ,&nbsp;Fuling Wu ,&nbsp;Mengqi Jiang","doi":"10.1016/j.bbrep.2025.102161","DOIUrl":"10.1016/j.bbrep.2025.102161","url":null,"abstract":"<div><div>As a chronic inflammatory disease of the lungs, bronchial asthma is closely associated with three key characteristics: airway inflammation, airway hyperresponsiveness, and airway remodeling. The long-term infiltration of multiple inflammatory cells into the airway interstitium results in damage to the airway epithelial barrier. Macrophages, as the primary immune cells responsible for the clearance of damaged and apoptotic cells from the asthmatic airways, phagocytose asthmatic cells through a series of efferocytosis phases, including the “find me,” “eat me,” and “digest” phases. This process, which involves the phagocytosis of apoptotic inflammatory and epithelial cells, serves to reduce airway epithelial damage and protect immune homeostasis. However, the cytosolic burial process of macrophages in asthma patients often exhibits dysfunctions, including reduced phagocytic efficiency, disorders of cytosolic burial signaling molecules, and the activation of airway inflammation. These impede the clearance process of inflammatory cells from the airway epithelium and necessitate the formation of temporary protective barriers. Barriers are formed through epithelial-mesenchymal transition, which impairs the regenerative capacity of the damaged epithelium and its barrier function, leading to an imbalance in epithelial-mesenchymal homeostasis. This, in turn, results in the occurrence of airway remodeling, which further exacerbates the process of asthma development. Intact and efficient efferocytosis serves as a critical regulatory mechanism in maintaining inflammatory homeostasis and suppressing epithelial-mesenchymal transition. Therapeutic modulation of macrophage-mediated efferocytosis represents a promising strategy for bronchial asthma intervention. In this paper, we present an overview of the specific stages of efferocytosis and the molecular mechanisms underlying the defects in efferocytosis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102161"},"PeriodicalIF":2.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing reveals altered immune and stromal landscape in primary and liver metastasis of gastric cancer","authors":"Bin Zhou ,&nbsp;Xiaolin Liu ,&nbsp;Huanhuan Hu ,&nbsp;Zhipeng Li ,&nbsp;Shanliang Zhong","doi":"10.1016/j.bbrep.2025.102163","DOIUrl":"10.1016/j.bbrep.2025.102163","url":null,"abstract":"<div><h3>Background</h3><div>We aimed to identify stromal cells associated with liver metastasis of gastric cancer (GC).</div></div><div><h3>Methods</h3><div>We downloaded single-cell RNA sequencing (scRNA-seq) datasets for GC tissues and adjacent normal tissues (NT), as well as liver metastases (LM) and healthy liver tissues (HL) from GEO. Additionally, we obtained RNA-Seq and clinical data from TCGA for the TCGA-STAD project. The datasets were analyzed using R software. Cell viability analysis were used to verify the potential drugs.</div></div><div><h3>Results</h3><div>We obtained 7 GC, 2 NT, 5 LM and 3 HL datasets, as well as 448 RNA-Seq files. We identified 13 cell types from a total of 107,875 cells, which were further re-clustered into 38 subclusters. Our analyses showed that both GC and LM exhibited increased angiogenesis, cancer-associated fibroblasts (CAFs) were enriched in primary tumors, CD8⁺ T cells in both GC and LM showed a declined proportion and increased necroptosis, NK cells were reduced in LM, and M2 macrophages (Mφ) exhibited high activities in both GC and LM. We found immune cells in HL and LM expressed more transcripts, suggesting the differences in tumor microenvironment (TME) between primary and metastatic tumors. Additionally, we identified 3 potential drugs that could be effective against both primary and metastatic tumors.</div></div><div><h3>Conclusion</h3><div>This study illustrated the heterogeneity of immune and stromal cells in TME of GC and LM, and identified several cell types associated with liver metastasis of GC. These cell types may serve as potential biomarkers or therapeutic targets in the future.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102163"},"PeriodicalIF":2.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatoma-derived growth factor and non-coding RNA network in ovarian cancer patients","authors":"Reza Ganjali ,&nbsp;Setare Nassiri ,&nbsp;Narges Zamani ,&nbsp;Zeinab Shaker-ardekani ,&nbsp;Mohammad Elahimanesh ,&nbsp;Nazanin Hosseinkhan ,&nbsp;Mitra Nourbakhsh","doi":"10.1016/j.bbrep.2025.102168","DOIUrl":"10.1016/j.bbrep.2025.102168","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer (OC) remains the most lethal gynecologic malignancy due to late diagnosis and limited effective biomarkers. Hepatoma-derived growth factor (HDGF) has emerged as an oncogene implicated in tumor progression, yet its regulation and clinical potential in OC remains underexplored. Recent evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) may modulate oncogenic pathways through competing endogenous RNA (ceRNA) networks.</div></div><div><h3>Methods and results</h3><div>Fifty ovarian cancer and fifty normal ovarian tissue samples were analyzed for HDGF, miR-345-5p, and LINC00839 expression using qRT-PCR. Bioinformatic tools were employed to predict RNA-RNA interactions and reconstruct a ceRNA network. Statistical analyses examined expression correlations and diagnostic performance via ROC curve. HDGF and LINC00839 were significantly upregulated, while miR-345-5p was downregulated in OC tissues (p &lt; 0.001). HDGF expression correlated positively with LINC00839 (r = 0.70) and inversely with miR-345-5p (r = −0.58), suggesting a regulatory axis where LINC00839 sponges miR-345-5p to derepress HDGF. Elevated HDGF levels were associated with larger tumor size, advanced FIGO stage, and metastasis. ROC analysis revealed that HDGF serum level (AUC = 0.88) has promising diagnostic potential, albeit lower than CA-125 and HE4.</div></div><div><h3>Conclusion</h3><div>Our study highlights the LINC00839–miR-345-5p–HDGF axis as a key regulatory network in ovarian cancer. HDGF may serve as a clinically relevant biomarker for disease progression, while LINC00839 and miR-345-5p represent promising therapeutic targets. These findings provide a foundation for future investigations into ceRNA-based diagnostics and treatments in OC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102168"},"PeriodicalIF":2.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of lipoprotein (a) [Lp(a)] gene polymorphic sequence variations and its protein expression in venous thromboembolism (VTE)","authors":"Karan Happa ,&nbsp;Arshad A. Pandith ,&nbsp;Umar H. Khan ,&nbsp;Shayaq Ul Abeer Rasool ,&nbsp;Aabid M. Koul ,&nbsp;Qurat Ul Ain ,&nbsp;Mir Uzair ul Haq ,&nbsp;Usma Manzoor ,&nbsp;Adil Lateef ,&nbsp;Rafi A. Jan","doi":"10.1016/j.bbrep.2025.102152","DOIUrl":"10.1016/j.bbrep.2025.102152","url":null,"abstract":"<div><h3>Background</h3><div>Venous thromboembolism (VTE) is a significant global health concern, with an annual incidence of approximately 1–2 per 1000 individuals. VTE is a major cause of morbidity and mortality worldwide, leading to substantial healthcare costs due to hospitalizations, long-term anticoagulation therapy, recurrent thrombotic events and the need for lifelong clinical management. The burden of VTE is particularly pronounced in aging populations, with incidence rates increasing exponentially after the age of 50. Despite its significant impact, the genetic underpinnings of VTE remain incompletely understood. This study investigates the association of Lp(a) gene polymorphisms (93C &gt; T and 121G &gt; A) and Lp(a) expression with VTE risk.</div></div><div><h3>Methods</h3><div>A case-control study was conducted, enrolling 101 VTE cases and 110 healthy, age- and gender-matched controls. Genotyping was performed using PCR-RFLP, and serum Lp(a) levels were quantified using ELISA. Genotype distribution and their association with VTE risk was determined by statistical analyses.</div></div><div><h3>Results</h3><div>The +121 G &gt; A polymorphism exhibited a significant protective effect, with the GA genotype more prevalent in controls than cases (OR = 0.41, 95 % CI = 0.23–0.73, p = 0.002). Additionally, the combined GA + AA genotypes were significantly associated with a lower VTE risk (OR = 0.44, p = 0.003). Serum Lp(a) levels were elevated in VTE cases (mean VTE 36.41 mg/dl) compared to controls (mean 32.00 mg/dl, p &lt; 0.84). Notably, this difference was most pronounced in the 30–70 mg/dl subgroup (p &lt; 0.01). D-Dimer was significantly elevated in VTE (p &lt; 0.001) and GA + AA genotype was significantly more frequent in control subjects with D-Dimer levels &lt;500 ng/ml (OR = 0.23, 95 % CI = 0.05–0.95, p = 0.04. LP (a)+121 G &gt; A variant genotype was significantly higher in controls for males, smokers and BMI ≤25 than VTE cases (p &lt; 0.05). No significant difference was found in LP(a) +93C &gt; T with VTE risk.</div></div><div><h3>Conclusion</h3><div>Our study concludes the inverse role of Lp(a) polymorphic variation +121 G &gt; A in the pathogenesis of VTE. +93C &gt; T variant and serum lipoprotein (a) levels did not increase the risk of pathogenesis of VTE. However, gender specific impact of LP(a) on VTE is plausible.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102152"},"PeriodicalIF":2.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HbA1c levels in hemoglobin H disease","authors":"Pasiri Kerdsinchai ,&nbsp;Adisak Tantiworawit ,&nbsp;Worapaka Manosroi ,&nbsp;Piangrawee Niprapan ,&nbsp;Sirichai Srichairatanakool ,&nbsp;Teerachat Punnachet ,&nbsp;Nonthakorn Hantrakun ,&nbsp;Pokpong Piriyakhuntorn ,&nbsp;Thanawat Rattanathammethee ,&nbsp;Sasinee Hantrakool ,&nbsp;Chatree Chai-Adisaksopha ,&nbsp;Ekarat Rattarittamrong ,&nbsp;Lalita Norasetthada ,&nbsp;Kanda Fanhchaksai ,&nbsp;Pimlak Charoenkwan","doi":"10.1016/j.bbrep.2025.102165","DOIUrl":"10.1016/j.bbrep.2025.102165","url":null,"abstract":"<div><h3>Background</h3><div>Patients with beta-thalassemia have been shown to exhibit lower HbA1c levels, often correlating with reduced hemoglobin (Hb) concentrations. Similarly, individual with alpha-thalassemia, particularly those with hemoglobin H (HbH) disease, experience chronic hemolytic anemia, which may also influence HbA1c measurements. This study aimed to investigate the effect of alpha-thalassemia on HbA1c levels.</div></div><div><h3>Methods</h3><div>This cross-sectional study was conducted between September 2022 and April 2024 at the Tertiary care University Hospital. Non-diabetic patients with alpha-thalassemia (hemoglobin H disease) were enrolled and compared with age- and sex-matched control without thalassemia. Statistical analysis was performed using independent t-tests based on distribution of data. Linear regression analysis was used to assess the association between HbH disease and HbA1c levels.</div></div><div><h3>Results</h3><div>A total of 92 participants were enrolled, comprising 46 patients with HbH disease and 46 matched controls. The mean ± SD HbA1c levels were significantly lower in the HbH group (4.09 ± 0.64 %) compared to the control group (5.39 ± 0.50 %) (P &lt; 0.001). The mean difference in HbA1c levels between the two groups was −1.31 ± 0.12 % [95 % CI -1.54 to −1.07](P &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Patients with HbH exhibit significantly lower HbA1c levels compared to control group. These finding highlight the need to establish specific HbA1c reference ranges for patients with thalassemia to avoid misinterpretation in the diagnosis and management of diabetes mellitus.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102165"},"PeriodicalIF":2.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the TLR signaling pathway in the pathogenesis of glioblastoma multiforme with an emphasis on immunotherapy","authors":"Seyedeh Elham Norollahi ,&nbsp;Kosar Babaei ,&nbsp;Ali Rashidy-pour ,&nbsp;Bahman Yousefi ,&nbsp;Rasoul Baharlou ,&nbsp;Bahareh Farasati Far ,&nbsp;Amir Jalali ,&nbsp;Ali Akbar Samadani","doi":"10.1016/j.bbrep.2025.102149","DOIUrl":"10.1016/j.bbrep.2025.102149","url":null,"abstract":"<div><div>The most malignant brain tumor, glioblastoma multiforme (GBM), has a high mortality rate. Recently, translational elements in GBM therapy have emerged as novel therapeutic strategies in addition to conventional treatment methods. In this way, Toll-like receptor (TLR), PI3K/Akt/mTOR, MAPK/ERK, NOTCH, and other signaling pathways have recently become some of the main signaling pathways in brain tumors. The immunological reactions to brain tumors are mediated by these mechanisms. A family of proteins known as TLRs is essential to the natural defense mechanism because it can identify and react to infections and other danger signals. TLRs have dual functions in the glioma microenvironment including that they can initially activate the innate and adaptive immune responses that support antitumor activity and secondly, their activation can also contribute to tumor progression by promoting inflammation and immune evasion, as they are expressed on both immune cells and tumor cells. TLR agonists are receiving more attention in the treatment of glioma because some of them have demonstrated survival benefits in clinical studies when used in conjunction with immunotherapy, chemotherapy, radiation therapy, and immune checkpoint inhibitors. The most exciting use of TLR agonists is that they can be used as immunomodulators to avoid dose accumulation, boost the efficiency of other therapies, and, by upregulating PD-1, reinforce delayed immune checkpoint resistance against PD-1/PD-L1 inhibition. Therefore, the use of TLR agonists can lead to PD-L1 overexpression, which in turn enhances the efficacy of checkpoint inhibitors and triggers potent anticancer immune responses. In this article, we describe the function of the TLR signaling system, the cellular and molecular elements contributing to the etiology of glioblastoma multiforme, the connection between TLRs and glioma, and their significance for immunotherapy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102149"},"PeriodicalIF":2.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}