Bosnian Journal of Basic Medical Sciences (BJBMS)
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Global Immune-Nutrition-Inflammation Index as a novel comprehensive biomarker in predicting the radiation-induced trismus rates in locally advanced nasopharyngeal carcinoma patients
Get PDFIn this study, we aimed to evaluate whether the novel pretreatment Global Immune-Nutrition-Inflammation Index (GINI) can predict radiation-induced trismus (RIT) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients undergoing concurrent chemoradiotherapy (CCRT). Data of LA-NPC patients presenting without RIT were reviewed retrospectively. Any post-CCRT maximum mouth openings (MMO) ≤ 35 mm were considered RIT. The GINI index was calculated using the formula: GINI = (CRP x Monocytes x Platelets x Neutrophils) ÷ (Albumin x Lymphocytes). We used receiver operating characteristic (ROC) curve analysis to examine the potential correlation between pretreatment GINI measures and post-CCRT RIT status. Logistic regression analysis examined the independence of the association between confounding factors and RIT rates. The study comprised 230 participants, and 52 (22.6%) received an RIT diagnosis. The optimal pre-CCRT GINI cutoff that dichotomizes RIT rates was determined to be 1,424 (area under the curve [AUC]: 76%; sensitivity: 75.0%; specificity: 71.7%; J-index: 0.463). RIT incidence was significantly higher in the GINI ≥ 1424 group than in its GINI < 1424 counterpart (43.3% vs. 9.3%; hazard ratio: 4.76; P < 0.001). Multivariate logistic regression analysis revealed that a pre-CCRT GINI ≥ 1424 was an independent predictor of increased RIT rates after definitive CCRT in this patient group (P < 0.001). In conclusion, the present results revealed that elevated pre-CCRT GINI measures (≥ 1424) can efficiently and independently predict elevated RIT rates in LA-NPC patients after CCRT
Tumor-type agnostic, targeted therapies make a new step forward: The first tumor-agnostic approval of a HER2-targeted therapy
Get PDFOncologic treatment has recently undergone substantial therapeutic paradigm shifts, from classical tumor-specific and biomarker-agnostic approaches to more molecular, biomarker-specific, and tumor-agnostic. Tumor-type (histology) agnostic drugs work across cancer types and present a novel shift in precision oncology. Compared with traditional cancer therapies, this novel approach implies molecularly informed treatment strategies and enables targeted treatment regardless of tumor histology (type). Such drugs are usually utilized in small clinical cohorts with diverse tumor types sharing a common genomic event (molecular biomarker). One of the key elements of this approach is the presence of a common biomarker across many tumor types. Biomarker predicts response to the targeted drugs, as well as deciphers potential resistance mechanisms.
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Forkhead box O-1 regulates the biological behavior of BMP-2-induced human bone mesenchymal stem cells through mitochondrial dynamics and autophagy
Get PDFThis study explored the mechanism by which forkhead box O-1 (FoxO1) modulates the biological behaviors of bone mesenchymal stem cell (BMSC). Human BMSCs were cultured for seven days in Dulbecco’s modified Eagle medium (DMEM) containing bone morphogenetic protein-2 (BMP-2) and treated with a short hairpin-FoxO1 plasmid. The study assessed cell proliferation, migration, apoptosis, adenosine triphosphate (ATP) levels, mitochondrial DNA (mtDNA) levels, membrane potential (MMP), autophagy, and the levels of FoxO1, apoptosis-associated proteins, osteogenic differentiation-associated proteins, mitochondrial fusion and fission proteins, and mitochondrial autophagy-related proteins. The cells were also treated with the mitochondrial fusion activator MASM7 and the mitochondrial autophagy activator carbonyl cyanide 3-chlorophenylhydrazone (CCCP). The study evaluated whether mitochondrial dynamics and autophagy activation could rescue the FoxO1 knockdown-induced changes in BMSC biological behaviors, mitochondrial dynamics, and mitochondrial autophagy. BMP-2-induced BMSCs exhibited upregulated FoxO1 expression, enhanced proliferation and migration, and induced osteogenic differentiation, while FoxO1 knockdown inhibited BMP-2-induced BMSC proliferation, migration and osteogenic differentiation, increased apoptosis, and affected mitochondrial dynamics and autophagy. Promoting mitochondrial fusion partially reversed the regulatory effects of FoxO1 downregulation on mitochondrial autophagy and the inhibitory effects of FoxO1 silencing on BMP-2-induced BMSC biological behaviors. Activated mitochondrial autophagy facilitated the homeostasis of mitochondrial dynamics and partially counteracted the inhibitory effects of FoxO1 knockdown on BMP-2-induced BMSC biological behaviors. In conclusion, FoxO1 regulates mitochondrial dynamics and autophagy to modulate the osteogenic differentiation of BMP-2-induced human BMSCs
ALKBH5 modulates m6A modification to enhance acute myeloid leukemia resistance to adriamycin
Get PDFAcute myeloid leukemia (AML) is a fatal malignancy with rising incidence and low cure rates. This study aims to investigate the effect of alkB homolog 5 (ALKBH5)-mediated N6-methyladenosine (m6A) modification on adriamycin (ADR) resistance in AML. First, the levels of ALKBH5, taurine upregulated 1 (TUG1), YTH N6-methyladenosine RNA binding protein F2 (YTHDF2), euchromatic histone lysine methyltransferase 2 (EHMT2), and SH3 domain-binding glutamate-rich protein-like (SH3BGRL) were measured. IC50 values, cell proliferation, and apoptosis were determined. m6A levels were analyzed, and the binding interactions between TUG1 and YTHDF2, as well as TUG1 and EHMT2, were assessed. The stability of TUG1 and the enrichment of EHMT2 and H3K9me2 on the SH3BGRL promoter were confirmed. In vivo experiments were conducted to further validate the results. The findings revealed that ALKBH5 was overexpressed in both AML- and ADR-resistant cells, and silencing ALKBH5 reduced the ADR resistance of AML cells. ALKBH5 removed m6A modifications from TUG1, disrupting the interaction between YTHDF2 and TUG1, thereby stabilizing TUG1 expression. TUG1 bound to EHMT2, promoting H3K9me2 modification on the SH3BGRL promoter and suppressing SH3BGRL expression. Overexpression of TUG1 or knockdown of SH3BGRL reversed the suppressive effect of ALKBH5 knockdown on ADR resistance. In vivo, ALKBH5 knockdown inhibited ADR resistance in AML cells. In conclusion, ALKBH5 removed m6A modification to stabilize TUG1 expression in a YTHDF2-dependent manner, enhancing H3K9me2 levels on the SH3BGRL promoter and suppressing SH3BGRL expression, thus promoting ADR resistance in AML cells
Piezo1-driven mechanotransduction as a key regulator of cartilage degradation in early osteoarthritis
Get PDFOsteoarthritis (OA) is a prevalent degenerative disease characterized by pain and cartilage damage in its later stages, while early OA is marked by the loss of cartilage’s mechanical function. Recent studies suggest that Piezo1, a mechanotransducer, may contribute to cartilage degradation under abnormal physical stress. This study investigates the mechanism by which Piezo1 mediates the loss of cartilage’s mechanical properties. Using rat chondrocytes cultured in a 3D in vitro model, we found that fluid flow-induced physical stress activates constitutively expressed Piezo1, leading to increased catabolic activity and apoptosis, which, in turn, disrupts the matrix structure. Ex vivo cartilage experiments further demonstrated that the mechanical stress-induced loss of cartilage’s physical properties (approximately 10% reduction in relaxation modulus) is mediated by Piezo1 and depends on cell viability. Notably, Piezo1 agonists alone did not alter the mechanical behavior of cartilage tissue. In vivo, using an OA rat model induced by anterior cruciate ligament transection, we observed cartilage integrity degradation and loss of mechanical properties, which were partially mitigated by Piezo1 inhibition. RNA sequencing revealed significant modulation of the PI3K signaling and matrix regulation pathways. Collectively, this study demonstrates that Piezo1-mediated catabolic activity in chondrocytes is a key driver of the loss of cartilage’s mechanical function during the relaxation phase
Mechanism of action of exercise regulating intestinal microflora to improve spontaneous hypertension in rats
Get PDFHypertension is a prevalent cardiovascular disease. Exercise is widely recognized as an effective treatment for hypertension, and it may also influence the composition of the intestinal microflora. However, it remains unclear whether exercise can specifically regulate the intestinal microflora in the context of hypertension treatment. In this study, tail blood pressure in spontaneously hypertensive rats (SHR) was measured using a blood pressure meter after exercise intervention and fecal bacteria transplantation following exercise. Blood lipid levels were assessed using an automatic biochemical analyzer, and 16S rRNA sequencing was employed to analyze the intestinal microflora. Histological examinations of ileal tissue were conducted using HE and Masson staining. Intestinal permeability, inflammatory status, and sympathetic activity were evaluated by measuring the levels of diamine oxidase, D-lactic acid, C-reactive protein, interleukin-6, tumor necrosis factor-α, lipopolysaccharide, norepinephrine, angiotensin II, cyclic adenosine monophosphate, and cyclic guanosine monophosphate. Exercise was found to reduce blood pressure and blood lipid levels in SHR. It also improved the composition of the intestinal microflora, as evidenced by a reduced Firmicutes/Bacteroidetes ratio, an increase in bacteria that produce acetic and butyric acid, and higher Chao 1 and Shannon diversity indices. Furthermore, exercise reduced the thickness of the fibrotic and muscular layers in the ileum, increased the goblet cell/villus ratio and villus length, and decreased intestinal permeability, inflammatory markers, and sympathetic nerve activity. The intestinal microbial flora regulated by exercise demonstrated similar effects on hypertension. In conclusion, exercise appears to regulate the intestinal microflora, and this exercise-induced change in flora may contribute to improvements in hypertension in rats
Comprehensive malnutritional index for predicting clinical outcomes in locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy
Get PDFThe objective of this investigation was to assess the prognostic significance of the comprehensive malnutritional index (CNI) in patients with locally advanced rectal cancer (LARC) who underwent neoadjuvant chemoradiotherapy (nCRT) followed by surgery. A total of 240 LARC patients were recruited. The CNI was calculated using principal components analysis based on hemoglobin (Hb), total lymphocyte count (TLC), albumin (ALB), body mass index (BMI), and usual body weight percentage (UBW%). The patients were then categorized into two groups based on the median CNI value. Cox regression and survival analyses were performed. The CNI-low (120 cases) and CNI-high (120 cases) groups were classified based on the median CNI value. The results indicated that the CNI demonstrated superior predictive ability for disease-free survival (DFS) and overall survival (OS) compared to other malnutritional indexes. LARC patients in the CNI-high group had significantly longer DFS and OS compared to those in the CNI-low group. Multivariate analysis revealed that the CNI was an independent prognostic factor for DFS (hazard ratio [HR] = 0.49; 95% confidence interval [CI], 0.29–0.83; P = 0.008) and OS (HR = 0.30; 95% CI, 0.16–0.58; P < 0.001). Additionally, the CNI-high group benefited from postoperative chemotherapy (DFS: P = 0.029, OS: P = 0.024), while the CNI-low group did not show such benefits (DFS: P = 0.448, OS: P = 0.468). These findings suggest that the CNI could serve as a valuable prognostic indicator for LARC patients who undergo nCRT followed by surgery. Preoperative nutrition optimization is important for LARC patients
Risk factors and a nomogram for predicting valproic acid-induced liver injury : A nested case-control study
Get PDFThe risk factors for liver injury induced by valproic acid (VPA) are not well understood, and no predictive tool currently exists to identify patients at risk. This study aims to explore these risk factors and develop a predictive model. We collected medical data from patients treated with VPA between January 1, 2020, and October 31, 2023. Prescription sequence analysis was used to identify patients with suspected VPA-induced liver injury, and the Roussel Uclaf Causality Assessment Method was applied to confirm the diagnosis. Risk factors were analyzed using logistic regression, and a nomogram model was developed and evaluated. A total of 256 cases were included in the study: 64 in the VPA-induced liver injury group and 192 in the control group. The incidence of liver injury was 5.3%. Multivariate logistic regression analysis revealed that dysglycemia (odds ratio [OR] = 5.171; 95% confidence interval [CI]: 1.254–21.325), hyperlipidemia (OR = 4.903; 95% CI: 1.400–17.173), surgery (OR = 10.020; 95% CI: 1.737–57.805), and hypokalemia (OR = 10.407; 95% CI: 2.398–45.173) were significant independent risk factors for VPA-induced liver injury. The area under the receiver operating characteristic curve was 0.904 (95% CI: 0.860–0.947), indicating excellent model performance. The Hosmer–Lemeshow test yielded a P value of 0.2671, and the calibration plot slope was close to one, further supporting the model’s accuracy. The findings suggest that patients with dysglycemia, hyperlipidemia, a history of surgery, and hypokalemia are at higher risk for VPA-induced liver injury. The nomogram model provides a reliable method for predicting the likelihood of liver injury in these patients
Epidemiological survey on prevalence and subtypes distribution of Blastocystis sp. in Southern Guizhou, China
Get PDFBlastocystis sp. is one of the most common intestinal protozoan parasites of humans worldwide and often has genetic polymorphisms. Due to its high prevalence and the possibility of potential transmission to humans, this study was carried out to investigate the prevalence of Blastocystis sp. and characterize its subtypes (genotypes) in southern Guizhou, China. A total of 548 fecal samples were collected from hospital patients for culture-based diagnosis. PCR products were sequenced and phylogenetically analyzed to identify subtypes and analyze their distribution. 43 positive cases of infection with Blastocystis sp. were detected, resulting in an overall prevalence of 7.85% (43/548). Seven subtypes were identified: ST3 (55.81%), ST1 (25.58%), ST7 (6.98%), ST5 (4.65%), ST2 (2.33%), ST4 (2.33%), and ST15 (2.33%). ST3 demonstrated the lowest intra-ST diversity, followed by ST1. Blastocystis sp. infection in southern Guizhou was caused by seven subtypes (ST1–ST5, ST7 and ST15) of the parasite, in which ST3 was the most common subtype, followed by ST1. The lowest intra-ST diversity of ST3 may be associated with substantial interhuman transmission in Guizhou. ST15 was found for the first time in humans, suggesting that it has the potential to be a zoonotic parasite. These findings have enhanced our understanding of the epidemiology and transmission of Blastocystis sp. in Southern Guizhou, China
Association of plasma endocan levels with metabolic parameters and predictive value of endocan for the development of complications in patients with type 2 diabetes mellitus: An observational study
Get PDFThe aim of the current research was to investigate the association between plasma endocan levels and metabolic control parameters, as well as to evaluate its predictive value for clinical complications in patients with type 2 diabetes mellitus (DMT2). A total of 100 DMT2 patients participated in this prospective observational study. Plasma endocan levels were significantly elevated in DMT2 patients with HbA1c > 7% (1.38 ± 0.33 vs 0.68 ± 0.23 ng/mL; P < 0.0001), compared to patients with HbA1c ≤ 7%. Patients with plasma endocan concentrations >1.10 ng/mL (median value of 1.10 ng/mL) demonstrated significantly higher levels of metabolic parameters: body mass index (BMI), HbA1c (%), fasting glucose level, LDL cholesterol, total cholesterol, triglycerides, along with significantly lower HDL cholesterol levels. Furthermore, patients with plasma endocan levels >1.10 ng/mL were found to have an increased risk for the following complications: retinopathy (relative risk [RR]: 2.7500; 95% confidence interval [CI]: 1.2150–6.2244; P = 0.0152, nephropathy (RR: 2.0952; 95% CI: 1.2294–3.5710; P = 0.0065), neuropathy (RR: 1.9945; 95% CI: 1.2025–3.3081; P = 0.0075), angina pectoris (RR: 2.4881; 95% CI: 1.0865–5.6979; P = 0.0311, hypertension (RR: 1.1372; 95% CI: 1.0060–1.2856; P = 0.0398), cardiomyopathy (RR: 2.6190; 95% CI: 1.1507–5.9612; P = 0.0218), myocardial infarction (RR: 9.4286; 95% CI: 1.2742–69.7697; P = 0.0280) and stroke (RR: 4.4638; 95% CI: 1.3765–14.4758; P = 0.0127). Correlation analysis revealed that plasma endocan levels were positively correlated with HbA1c (%) (r = 0.856, P < 0.0001), fasting glucose level (r = 0.631, P < 0.0001), LDL (r = 0.347, P = 0.0004), cholesterol (r = 0.282, P = 0.0045), and triglycerides (r = 0.366, P = 0.0002). Conversely, plasma endocan levels were negatively correlated with HDL cholesterol (r = −0.429, P < 0.0001). In conclusion, higher plasma endocan levels were strongly associated with poor metabolic control in DMT2 patients and exhibited significant predictive value for both microvascular and macrovascular complications