Biomedical reports最新文献

ETS variant transcription factor 6 (ETV6)-neurotrophic receptor tyrosine kinase 3 (NTRK3) (EN) fusions are typically found in rare diseases, such as primary renal fibrosarcoma (only six cases have been reported), secretory carcinoma of the breast and salivary gland (1 case), and AML (4 cases). Few cases have been reported, and expression of the EN gene fusion requires additional clinical data and fundamental research to be supported. The aim of the present study was to determine the inhibitory effect of Andrographis paniculata methanol extract (MeAP) on EN-related cell lines, IMS-M2 and BaF3/EN, as well as evaluate the mechanism of action. Vero cells were used as control cells. Trypan blue staining and MTT were used to evaluate the inhibitory effect of MeAP on tested cells. Western blotting and immunoprecipitation were used to detect the activation of EN after MeAP treatment. The IC₅₀ values of MeAP were found to be 12.38±0.57 µg/ml (IMS-M2) and 13.06±0.49 µg/ml (BaF3/EN). MeAP was observed to inhibit cell proliferation in a time, dose, and cell density-dependent manner. The IC₅₀ value for MeAP in Vero cells was markedly higher, at 109.97±4.24 (µg/ml), indicating a much less sensitive effect. Furthermore, MeAP treatment inhibited EN phosphorylation and induced apoptosis in these cells. Collectively, the present study demonstrated that MeAP has an oncogenic effect on EN fusion-positive cell lines, in particular.

Acute pancreatitis is characterized as an inflammatory illness that is life-threatening and causes necrosis as well as simple edema when pancreatic enzymes are activated intraglandularly. It is not known whether severe acute respiratory syndrome coronavirus 2 causes acute pancreatitis. Patients with acute pancreatitis who test positive for coronavirus disease 2019 (COVID-19) frequently have biliary or alcoholic causes. It is unclear how common acute pancreatitis is in patients with COVID-19. By contrast with patients without COVID-19, however, COVID-19-positive patients with acute pancreatitis have a higher mortality as well as a higher risk of necrosis and admission to an intensive care unit. The most common cause of mortality in COVID-19-positive individuals with concurrent severe pancreatitis is acute respiratory distress syndrome. The present study discussed research on the link between COVID-19 infection and acute pancreatitis.

Vaccination against hepatitis B virus (HBV) remains the most effective strategy against HBV infection in humans. The present review summarized the optimal vaccination strategies against HBV in childhood. The following points are discussed: i) When and how the first HBV vaccines were developed; ii) the dosages, schedules and injection routes that are used for HBV vaccination; iii) the contraindications for HBV vaccination in the general paediatric population; iv) the challenges with the use of multivalent vaccines; v) the long-term immunogenicity and duration of protection against HBV; vi) the use of selective HBV vaccination and the hepatitis B immune globulin strategy in HBV-exposed infants; and vii) the effectiveness of the current HBV vaccination schemes. The present review is based on a Paediatric Virology Study Group (PVSG) webinar performed in the context of the 8th Workshop on Paediatric Virology.

Gemcitabine is a chemotherapeutic agent for pancreatic cancer treatment. It has also been demonstrated to inhibit human pancreatic cancer cell lines, MIA PaCa-2 and PANC-1. The aim of the present study was to investigate the suppressive effect of fucoxanthin, a marine carotenoid, in combination with gemcitabine on pancreatic cancer cells. MTT assays and cell cycle analysis using flow cytometry were performed to study the mechanism of action. The results revealed that combining a low dose of fucoxanthin with gemcitabine enhanced the cell viability of human embryonic kidney cells, 293, while a high dose of fucoxanthin enhanced the inhibitory effect of gemcitabine on the cell viability of this cell line. In addition, the enhanced effect of fucoxanthin on the inhibitory effect of gemcitabine on PANC-1 cells was significant (P<0.01). Fucoxanthin combined with gemcitabine also exerted significant enhancement of the anti-proliferation effect in MIA PaCa-2 cells in a concentration dependent manner (P<0.05), compared with gemcitabine treatment alone. In conclusion, fucoxanthin improved the cytotoxicity of gemcitabine on human pancreatic cancer cells at concentrations that were not cytotoxic to non-cancer cells. Thus, fucoxanthin has the potential to be used as an adjunct in pancreatic cancer treatment.

The present study aimed to demonstrate the proportion of the programmed death-ligand 1 (PD-L1) expression in penile cancer patients and the association with clinicopathological parameters. Formalin-fixed paraffin-embedded specimens were obtained from 43 patients with primary penile squamous cell carcinoma treated at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, between 2008 and 2018. PD-L1 expression was evaluated by the immunohistochemistry using an SP263 monoclonal antibody. PD-L1 positivity was defined as >25% tumor cell staining or >25% tumor-associated immune cell staining. The correlation between PD-L1 expression and clinicopathological parameters was analyzed. A total of eight of 43 patients (18.6%) were identified as positive for PD-L1 expression in tumor cells and tumor-infiltrating lymphocytes. In the PD-L1 positive group, there was a significant association with pathological T stage (P=0.014) with a higher percentage of PD-L1 positive tumors in T1 stage compared with T2-T4 stage. In this cohort, there was a trend towards longer survival in patients with positive PD-L1 expression (5-year OS: 75% vs. 61.2%, P=0.19). Lymph node involvement and the location of tumor at the shaft of penis were two independent prognostic factors for survival. In conclusion, the PD-L1 expression was detected in 18% of penile cancer patients and high expression of PD-L1 was associated with the early T stage.

Hypertension is an important risk factor for cardiovascular and cerebrovascular disease-associated death. Hypertension and its complications are the main problems that have an impact on public health at present. A portion of adults with hypertension fail to meet the recommended blood pressure (BP) treatment goals, despite strict clinical management. Those individuals requiring at least three types of antihypertensive drugs to achieve their BP goal may be classified as patients with resistant hypertension (RH). Bioelectric technology is an emerging method that functions with the help of the human body's own bioelectric system. It is widely used in auxiliary examination, pain relief and organ function rehabilitation. Bioelectrical technology, as an effective treatment for RH, has developed rapidly in recent years and mainly includes renal sympathetic denervation, carotid baroreflex activation therapy, Traditional Chinese Medicine electroacupuncture and transcutaneous electrical nerve stimulation (TENS). The present review describes the pathogenesis of hypertension and provides an understanding of bioelectrical technology as a treatment. In particular, the development of the application of TENS in RH is introduced. The aim is to provide a basis for the clinical treatment of RH and a new idea for further clinical trials in this field.

The electrocardiogram (ECG) changes in patients with intraparenchymal hemorrhage (IPH) have remained largely elusive and no case reports are currently available in the scientific literature. The medical management of a patient with ST-segment elevation associated with IPH was described in the present study. The case report describes a 78-year-old male patient who presented with ST-segment elevation in V1, V2, V3 and V4 on ECG. Initially, the case was managed therapeutically as an acute myocardial infarction. Later, the patient was transferred to a higher-level hospital, where a new ECG confirmed ST-segment elevation. Simple skull tomography was also performed, which revealed a spontaneous right basal ganglion in the context of an acute cerebrovascular accident of hypertensive origin. A transthoracic ECG was ordered, which revealed an ejection fraction of 65% with type I diastolic dysfunction due to relaxation disorders and without any signs of ischemia, intracavitary masses or thrombi. In addition to the presence of nonspecific ECG findings, clinicians should consider immediate brain computed tomography to confirm intracranial hemorrhage.

Osteoarthritis (OA) is one of the most common degenerative joint diseases leading to disability in the end stage. Although intra-articular triamcinolone acetonide (TA) is one of the OA treatments that have been widely used, the side effects of such corticosteroids are still controversial. Intra-articular hyaluronic acid (HA) injection is another therapeutic option for patients with OA who do not want to use corticosteroids because of their side effects. However, the difference between the histological features associated with TA and HA in the treatment of OA remains unclear. Thus, the present study aimed to compare the histological effects of TA and HA on the cartilage of patients with knee OA. In the current study, 31 patients diagnosed with grade 3-4 knee OA on the Kellgren-Lawrence radiographic grading scale were separated into three groups: TA (n=12); HA (n=7) and untreated group (n=12). Histological examination of the whole articular cartilages of the patients was performed with hematoxylin and eosin and Alcian staining, as well as using a TUNEL assay. Clinical data such as cartilage thickness, structural and component deterioration, proteoglycan levels, apoptosis and empty lacunae were compared between the three groups. The results showed a high level of deterioration in both TA and HA groups but not in the untreated group, although the thickness of cartilage in the HA group was lower compared with that in the TA and untreated groups. The proteoglycan levels in the TA group were lower compared with those in the HA group. Moreover, the number of empty lacunae in the HA group was higher compared with that in the TA group, while no difference in apoptosis was found between TA and HA groups. A significant difference was not found in the histological staining between TA and HA groups. On the other hand, a significant difference was found in cartilage deterioration between the medial and lateral sides in these groups. TA and HA groups showed comparable histological results. TA injection is cheaper and easier but has more adverse effects for patients with knee OA than HA injection. Therefore, orthopaedists should select TA or HA based on the economic and specific needs of patients.

Numerous physiological processes occur following bone fracture, including inflammatory cell recruitment, vascularization, and callus formation and remodeling. In particular circumstances, such as critical bone defects or osteonecrosis, the regenerative microenvironment is compromised, rendering endogenous stem/progenitor cells incapable of fully manifesting their reparative potential. Consequently, external interventions, such as grafting or augmentation, are frequently necessary. In situ bone tissue engineering (iBTE) employs cell-free scaffolds that possess microenvironmental cues, which, upon implantation, redirect the behavior of endogenous stem/progenitor cells towards a pro-regenerative inflammatory response and reestablish angiogenesis-osteogenesis coupling. This process ultimately results in vascularized bone regeneration (VBR). In this context, a comprehensive review of the current techniques and modalities in VBR-targeted iBTE technology is provided.

Endometriosis is characterized by the presence of endometrial-like tissue outside the uterus and is associated with an inflammatory immune response. The gut and reproductive tract microbiota constitute a protective barrier against infection by pathogens and regulate inflammatory and immune functions. This review summarizes microbiota imbalance (i.e., dysbiosis) in endometriosis and discusses how dysbiosis influences disease development. The literature was searched for studies published from inception to March 2022 in the PubMed and Google Scholar databases using a combination of specific terms. An altered gut and reproductive tract microbiome has been reported in numerous conditions, such as inflammatory bowel disease, allergies, autoimmunity, cancer and reproductive disorders (e.g., endometriosis). Furthermore, microbial dysbiosis is a hallmark of endometriosis and is characterized by a decrease in beneficial probiotics and an increase in pathogenic microbes, which leads to a series of estrobolomic and metabolomic changes. Gut or reproductive tract microbiome dysbiosis was reported in mice, nonhuman primates, and females with endometriosis. Animal models of endometriosis demonstrated the effects of the gut microbiome on lesion growth and vice versa. The immune system mediated by the microbiota-gut-reproductive tract axis triggers an inflammatory response that damages reproductive tract tissue, which possibly leads to endometriosis. However, whether the alteration of eubiosis (a balanced microbiota) to dysbiosis is a cause or a result of endometriosis is unclear. In conclusion, this review provides an overview of the relationship between the gut and reproductive tract microbiome and endometriosis, focusing on the mechanisms by which dysbiosis may increase the risk of disease.