Bosnian Journal of Basic Medical Sciences (BJBMS)
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A novel homozygous exon2 deletion of TRIM32 gene in a Chinese patient with sarcotubular myopathy: A case report and literature review
Get PDFSarcotubular myopathy (STM) is a rare autosomal recessive myopathy caused by TRIM32 gene mutations. It is predominantly characterized by the weakness of the proximal limb and mild to moderate elevation of creatine kinase (CK) levels. In this study, we describe a 50-year-old Chinese man who exhibited a proximal-to-distal weakness in the muscles of the lower limbs and who had difficulty standing up from a squat position. The symptoms gradually became more severe. He denied a history of cognitive or cardiological problems. The patient’s parents and children were healthy. Histopathological examination revealed dystrophic changes and irregular slit-shaped vacuoles containing amorphous materials. Whole-exome sequencing consisting of protein-encoding regions of 19,396 genes was performed, the results of which identified one novel homozygous 2kb deletion chr9.hg19: g.119460021_119461983del (exon2) in the TRIM32 gene. This was confirmed at the homozygous state with quantitative real-time PCR. Here, we present a Chinese case of STM with one novel mutation in TRIM32 and provide a brief summary of all known pathogenic mutations in TRIM32
Analysis of the diagnostic and prognostic value of miR-9-5p in carotid artery stenosis
Get PDFMore and more evidence shows that microRNAs (miRNAs) play an important role in the diagnosis and prognosis of human diseases. In this study, we investigated the diagnostic value of miR-9-5p for asymptomatic carotid artery stenosis (CAS) and its predictive value for future cerebrovascular events within 5 years. A total of 88 asymptomatic CAS patients and 86 healthy individuals were recruited. The expression level of serum miR-9-5p was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic value of miR-9-5p in CAS was assessed by a receiving operator characteristic (ROC) curve. The predictive value of miR-9-5p for the occurrence of cerebrovascular events was evaluated by the Kaplan-Meier method. The serum level of miR-9-5p was significantly decreased in asymptomatic CAS patients. ROC curve had an AUC value of 0.910, with the sensitivity and specificity of 80.7% and 87.2% at the cut-off value of 0.72, respectively. A total of 25 patients had cerebrovascular events during the 5-year follow-up, including 3 strokes and 22 transient ischemic attacks (TIAs). Kaplan-Meier survival analysis revealed that the low expression level of miR-9-5p was an independent factor closely related to the occurrence of cerebrovascular events. Serum miR-9-5p could be used as a new biomarker for the diagnosis of CAS, and the low expression of miR-9-5p is associated with poor prognosis
Letter regarding “Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis”
Get PDFDear Editor:
We have read with a great interest the article by Gupta et al. [1] who performed a meta-analysis exploring the association between chronic mechanical irritation and oral squamous cell carcinoma. The conclusion of the meta-analysis is that chronic oral mucosa irritation has a significant association with oral squamous cell carcinoma, and the nature of association could be that of a potential co-factor (dependent risk factor) rather than an independent risk factor.
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Combined inhibition of ACK1 and AKT shows potential toward targeted therapy against KRAS-mutant non-small-cell lung cancer
Get PDFNon-small-cell lung cancer (NSCLC) with Kirsten RAt Sarcoma 2 viral oncogene homolog (KRAS) mutation has become a clinical challenge in cancer treatment as KRAS-mutant tumors are often resistant to conventional anti-tumor therapies. Activated CDC42-associated kinase 1 (ACK1), an activator of protein kinase B (AKT), is a promising target for KRAS-mutant tumor therapy, but the downstream ACK1 signaling remains poorly understood. The aim of this study was to evaluate the effectiveness of combined ACK1/AKT inhibition on the proliferation, migration, invasion, and apoptosis of KRAS-mutant NSCLC cell lines (NCI-H23, NCI-H358, and A549). The cells were treated with an inhibitor of either ACK1 (dasatinib or sunitinib) or AKT (MK-2206 or GDC-0068), and the optimal concentrations of the two yielding synergistic tumor-killing effects were determined by applying the Chou-Talalay equation for drug combinations. We showed that combined administration of ACK1 and AKT inhibitors at the optimal concentrations effectively suppressed NSCLC cell viability and promoted apoptosis while inducing cell cycle arrest at the G2 phase. Moreover, NSCLC cell migration and invasion were inhibited by combined ACK1/AKT inhibition. These phenomena were associated with the reduced phosphorylation levels of ACK1 and AKT (at Ser473 and Thr308), as well as alterations in caspase-dependent apoptotic signaling. Collectively, our results demonstrate the promising therapeutic potential of combined ACK1/AKT inhibition as a strategy against KRAS-mutant NSCLC. Our findings provide the basis for the clinical translation of biological targeted drugs (ACK1 and AKT inhibitors) and their rational combination in cancer treatment
Dose-dependent effects of adalimumab in neonatal rats with hypoxia/reoxygenation-induced intestinal damage
Get PDFTumor necrosis factor-alpha (TNF-α) has an important role in hypoxia/reoxygenation (H/R)-induced intestinal damage. It was shown that blocking TNF-α with infliximab has beneficial effects on experimental necrotizing enterocolitis and hypoxic intestinal injury. However, there is no data about the effect of adalimumab on H/R-induced intestinal damage. Therefore, we aimed to determine potential dose-dependent benefits of adalimumab in such damage in neonatal rats. Wistar albino rat pups were assigned to one of the four groups: control group, hypoxia group, low-dose adalimumab (5 mg/kg/day) treated group (LDAT), and high-dose adalimumab (50 mg/kg/day) treated group (HDAT). On the fourth day of the experiment, all rats except for the control group were exposed to H/R followed by euthanasia. Malondialdehyde (MDA), myeloperoxidase (MPO), TNF-α, total antioxidant capacity (TAC), and total oxidant capacity (TOC) were measured in intestinal tissue. TAC and TOC values were used to calculate the oxidative stress index (OSI). Histopathological injury scores (HIS) were also evaluated in the tissue samples. MDA levels were significantly lower in the LDAT and HDAT groups (p < 0.001). TNF-α levels were significantly lower in the LDAT group (p < 0.001). OSI was significantly higher in the H/R group than in the control and LDAT groups (p < 0.001). Mean HIS values in the LDAT group were significantly lower than those in the H/R and HDAT groups (p < 0.001). This experimental study showed that low-dose adalimumab appears to have a beneficial effect on intestinal injury induced with H/R in neonatal rats
Targeting HER2 expression in cancer: New drugs and new indications
Get PDFFunctional activation of human epidermal growth factor receptor 2 (HER2) has been shown to strongly promote carcinogenesis, leading to the investigation of HER2-directed agents in cancers with HER2 genomic alterations. This has been best documented in the context of HER2 gene amplification in breast and gastric/gastroesophageal junction carcinomas for which several HER2-directed agents are available and have become a part of standard treatment regimens. Somatic HER2 gene mutations have been recently described at low frequency in a variety of human cancers and have emerged as a novel predictive biomarker for HER2-directed therapies. Preclinical data also indicate that activating HER2 mutations are potent oncogenic drivers in a manner that is analogous to HER2 amplification. HER2 mutations may clinically confer sensitivity to HER2-directed agents as recently shown in a phase II clinical trial with antibody-drug conjugate against HER2 trastuzumab deruxtecan in patients with non-squamous non-small cell lung carcinoma
LncRNA SENCR suppresses abdominal aortic aneurysm formation by inhibiting smooth muscle cells apoptosis and extracellular matrix degradation
Get PDFAbdominal aortic aneurysm (AAA) is a progressive chronic dilatation of the abdominal aorta without effective medical treatment. This study aims to clarify the potential of long non-coding RNA SENCR as a treatment target in AAA. Angiotensin II (Ang-II) was used to establish AAA model in vitro and in vivo. Reverse transcription quantitative PCR and western blot were performed to measure the expression of SENCR and proteins, respectively. Annexin V-FITC/PI double staining was carried out to detect the apoptotic rate in vascular smooth muscle cells (VSMCs), and cell apoptosis in aortic tissues was determined by TUNEL staining. Besides, hematoxylin and eosin and Elastica van Gieson staining were performed for histological analysis of aortic tissues. SENCR was downregulated in AAA tissues and Ang-II-stimulated VSMCs. Overexpression of SENCR could inhibit Ang-II-induced VSMC apoptosis, while inhibition of SENCR facilitated Ang-II-induced VSMC apoptosis. Moreover, the expression of matrix metalloproteinase (MMP)-2 and MMP-9 in Ang-II-induced VSMCs was reduced following SENCR overexpression, while tissue inhibitor of metalloproteinases 1 (TIMP-1) expression was increased. In vivo, overexpression of SENCR improved the pathological change in aortic tissues and the damage in arterial wall elastic fibers induced by Ang-II, as well as suppressed Ang-II-induced cell apoptosis and extracellular matrix degradation. Overall, SENCR was decreased in AAA. Overexpression of SENCR inhibited AAA formation via inhibition of VSMC apoptosis and extracellular matrix degradation. We provided a reliable evidence for SENCR acting as a potential target for AAA treatment
Cryptic t(15;17) acute promyelocytic leukemia with a karyotype of add(11)(p15) and t(13,20)- A case report with a literature review
Get PDFMost acute promyelocytic leukemia (APL) are characterized by reciprocal translocations t(15;17)(q22;21), which results in the fusion of PML gene at 15q22 with RARα gene at 17q21. However, several complex variant translocations also have been reported. Here we report a 62-year-old man with typical morphology and clinical features of APL with a complex karyotype including add(11)(p15) and t(13,20)(q12;q11.2) without typical t(15;17) assayed by the G-banding analysis. FISH with a PML/RARα dual-color DNA probe showed an atypical fusion signal, RT-qPCR analysis showed PML/RARα fusion transcripts, and NGS detected FLT3, WT1, and KRAS mutations. The patient achieved complete remission after treatment with conventional chemotherapy combined ATRA and ATO. Although the mechanism of this kind of cryptic variant remains unknown, we conclude that the cryptic PML/RARα fusion with add(11)(p15), t(13,20)(q12;q11.2) seems not to alter the effectiveness of chemotherapy combined with ATRA and ATO
Increasing the efficiency of mechanical ventilators during pandemics through additive manufacturing
Get PDFThe COVID-19 pandemic tested medical facilities’ readiness in terms of the number of available mechanical ventilators. Most countries raced to stock up on ventilators, which created a surge in demand and short in supply. Furthermore, other means of coping with the demand were proposed, such as using additive manufacturing. The purpose of this paper was to test whether the addition of 3D-printed splitters would help deliver required tidal volume to each patient, while supporting four patients on a single ventilator for 24 hours on pressure mode at 25-cm H2O, and to determine whether a fifth patient can be ventilated. The ventilation of four human lungs was simulated using 3D printed parts, a single ventilator, four test-lungs, and standard tubing. Peak pressure, positive end-expiratory pressure, total tidal volume, individual tidal volume, total minute volume, and individual tidal volume data were collected. Usage of a 3D printed small size splitter enabled a 26% increase in individual tidal volume compared to standard tubing and a series of two-way splitters. The ventilator was able to supply the required pressure and tidal volume for 24 hours. A single ventilator with a four-way splitter can ventilate four patients experiencing respiratory failure for at least 24 hours without interruption. The equipment cannot sustain ventilating a fifth patient owing to minute volume limitation. This study expands on an earlier study that tested similar circuitry and reveals that the desired individual tidal volume is achieved. However, further research is required to provide the monitoring ability of individual patient parameters and prevention of cross-contamination
Development and validation of a SEER-based prognostic nomogram for cervical cancer patients below the age of 45 years
Get PDFIn this study, we established a nomogram for the prognostic prediction of patients with early-onset cervical cancer (EOCC) for both overall survival (OS) and cancer-specific survival (CSS). The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 10,079 patients diagnosed with EOCC between 2004 and 2015; these cases were then randomly divided into training and validation sets. The independent prognostic factors were identified in a retrospective study of 7,055 patients from the training set. A prognostic nomogram was developed using R software according to the results of multivariable Cox regression analysis. Furthermore, the model was externally validated using the data from the remaining 3,024 patients diagnosed at different times and enrolled in the SEER database. For the training set, the C-indexes for OS and CSS prediction were determined to be 0.831 (95 % confidence interval [CI]: 0.815–0.847) and 0.855 (95 % CI: 0.839–0.871), respectively. Receiver operating characteristic (ROC) analysis has revealed that the nomograms were a superior predictor compared with TNM stage and SEER stage. The areas under the curve (AUC) of the nomogram for OS and CSS prediction in the ROC analysis were 0.855 (95 % CI: 0.847–0.864) and 0.782 (95 % CI: 0.760–0.804), respectively. In addition, calibration curves indicated a perfect agreement between the nomogram-predicted and the actual 1-, 3-, and 5-year OS and CSS rates in the validation cohort. Thus, in this study, we established and validated a prognostic nomogram that provides an accurate prediction for 3-, 5-, and 10-year OS and CSS of EOCC patients. This will be useful for clinicians in guiding counseling and clinical trial design for cervical cancer patients