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TM injection significantly increased BiP expression and modified the topographic expression patterns of the UPR signaling proteins. In addition, immunohistochemical analysis of Beclin1 revealed an increased pericentral staining intensity following TM pretreatment. The histologic analysis of hepatocellular damage demonstrated a significant reduction in cell death areas in HS/R+TM (P=0.024). ER stress preconditioning influences the UPR and alleviates post-hemorrhagic liver damage. The beneficial effects were, at least partially, mediated by the upregulation of BiP and autophagy induction. These results underscore the importance of the UPR in the context of HS/R and may help identify novel therapeutic targets.Neoadjuvant chemotherapy (NACT) has been considered to be the preferred treatment option for early operable triple-negative breast cancer (TNBC). However, resistance to drugs remains to be the barrier to the efficacy of NACT. Glucosylceramide synthase (GCS) and cytochrome P450 family 1 subfamily A1 (CYP1A1) have been previously associated with drug resistance in breast cancer. The present study aimed to explore whether the expression levels of GCS and/or CYP1A1 are associated with the prognosis of TNBC after NACT. Immunohistochemistry was used to detect and measure GCS and CYP1A1 expression. Associations between GCS or CYP1A1 expression and the clinicopathological characteristics, pathological complete response (pCR), clinical complete response (cCR) and disease-free survival (DFS) were analyzed. GCS expression was found to be associated with tumor size (P=0.021) and TNM staging (P=0.042), whilst CYP1A1 expression was associated with lymph node metastasis (P = 0.026) and TNM staging (P=0.034). this website The expression levels of GCS (P=0.024) and CYP1A1 (P=0.027) were upregulated after NACT. GCS and CYP1A1 expression were positively correlated (P=0.003; r=0.327). No difference was observed between the GCS+ (P=0.188) or CYP1A1+ group (P=0.073) and the GCS- or CYP1A1- group in terms of pCR. However, compared with that in the GCS+CYP1A1+ group, the pCR was markedly increased in the GCS-CYP1A1- group (P=0.031). The cCR was lower in the GCS+ (P=0.021) and CYP1A1+ groups (P=0.016) compared with in the GCS- or CYP1A1- group. The DFS rate (57.9 vs. 65.4%; P=0.049) was lower in the GCS+CYP1A1+ group compared with that in the GCS-CYP1A1- group. However, there was no statistical significance after P-value was adjusted for multiple comparisons using Bonferroni correction. In conclusion, co-expression of GCS and CYP1A1 was associated with pCR and DFS in TNBC, which may serve a role in the prediction of the prognosis of patients with TNBC following treatment with NACT.The prevalence of Gaucher disease (GD) in Japan is much lower than that in Western countries; therefore, data on Japanese pediatric patients with GD type 1 are currently limited. The present study reports on the case of a Japanese pediatric patient with GD type 1 who was diagnosed when she presented with hepatosplenomegaly, thrombocytopenia and slight anemia at the age of 2 years. Serology tests revealed high levels of acid phosphatase (ACP) and angiotensin-converting enzyme (ACE). A bone marrow biopsy revealed the presence of Gaucher cells. Abdominal MRI indicated huge hepatosplenomegaly. Erlenmeyer flask deformity was observed on X-ray examination. MRI of the femora featured a high-intensity area within the diaphysis region. The enzymatic activity of leukocyte β-glucosidase, the measurement of which is necessary for a definitive diagnosis of GD, had decreased to 186.7 nmol/h/mg (reference range, 1,424.0-2,338.0 nmol/h/mg). Based on these results, the patient was clinically diagnosed with GD. Glucocerebrosidase gene analysis identified the compound heterozygote mutation of F213I (c.754T>A) on exon 7 and L444P (c.1448T>C) on exon 11. Enzyme replacement therapy (ERT) along with an intravenous infusion of 60 U/kg of imiglucerase every other week was initiated following diagnosis. Hemoglobin levels and the platelet count gradually improved and normalized after two years. ACP and ACE levels, biomarkers of the progression of GD, also improved. Abdominal MRI at six months after the initiation of ERT revealed a decrease in the size of the liver and spleen, which normalized after 1 year. Conversely, MRI of the femora indicated no improvement in the high-intensity area within the diaphysis region for 10 years.New rehabilitation strategies enabled by technological developments are challenging the prevailing concept of there being a limited window for functional recovery after stroke. In this study, we examined the utility of a robot-assisted therapy used in combination with a serious game as a rehabilitation and motor assessment tool in patients with chronic stroke. We evaluated 928 game rounds from 386 training sessions of 8 patients who had suffered an ischemic stroke affecting middle cerebral artery territory that incurred at least 6 months prior. Motor function was assessed with clinical motor scales, including the Fugl-Meyer upper extremity (FM UE) scale, Action Research Arm Test, Modified Ashworth scale and the Box and Blocks test. Robotic device output measures (mean force, force-position correlation) and serious game score elements (collisions, rewards and total score) were calculated. A total of 2 patients exhibited a marginal improvement after a 10-week training protocol according to the FM UE scale and an additional patient exhibited a significant improvement according to Box and Blocks test. Motor scales showed strong associations of robotic device parameters and game metrics with clinical motor scale scores, with the strongest correlations observed for the mean force (0.677 less then Ρ less then 0.869), followed by the number of collisions (-0.670 less then Ρ less then -0.585). Linear regression analysis showed that these indices were independent predictors of motor scale scores. In conclusion, a robotic device linked to a serious game can be used by patients with chronic stroke and induce at least some clinical improvements in motor performance. Robotic device output parameters and game score elements associate strongly with clinical motor scales and have the potential to be used as predictors in models of rehabilitation progress.As one year is approaching since the beginning of the Coronavirus disease 2019 (COVID-19) pandemic, it is important to acknowledge the detrimental effect that it is having on mental health at the individual, societal and public health levels. The current review presents the direct and indirect psychological impact of COVID-19 on the general public, as well as on vulnerable groups, including the elderly, the young, healthcare professionals, people with pre-existing mental health issues, those infected by COVID-19, homeless people and refugees. Important findings are discussed in the present review, including the social stigma in older people associated with portraying COVID-19 as the disease of the elderly, and the limited psychological impact of COVID-19 in the severely mentally ill, alongside the response of the mental healthcare systems globally to this unparalleled public health crisis. The important lessons to be learnt so far can help formulate individual mental health recommendations, as well as improved intervention and prevention public health strategies.Ovarian endometriosis is a frequent chronic gynecological disease with an uncertain evolution regarding its progression or association with ovarian malignant lesions. The present review summarized the histological aspects, gene expression and microRNA (miRNA/miR) alterations associated with ovarian endometriosis and cancer and their possible interaction. The endometriosis-ovarian cancer interaction has been proposed by certain researchers as a single entity. Histological results indicated that endometriosis has been in different circumstances coexisting with ovarian cancer, with reference to endometrioid and clear cell carcinoma. Endometriosis with moderate and severe atypia can influence cell proliferation and architecture, resulting in a possible malignant transformation. Gene expression analysis indicated that the pathologies of both endometriosis and ovarian cancer are characterized by genetic instability from a molecular point of view, as several important genetic mutations, including ARID1A, PI3KCA, PTEN, BRCA1, BRCA2, TP53 and KRAS genes, were identified. miRNA alterations have been implicated in the regulation of gene expression. Common dysregulated miRNAs, such as miR-331, miR-335, miR-891, miR-548, miR-124, miR-148, miR-215, miR-192, miR-337, miR-153, miR-155, miR-144, miR-221 and miR-3688 were extensively investigated in understanding endometriosis and ovarian cancer evolution. From a combined viewpoint including histological aspects, gene expression and miRNA alterations, it is reasonable to speculate that endometriosis is associated with ovarian cancer. Ovarian endometriosis lesions may present a risk for ovarian malignant lesions, which supports a model of endometriosis as a malignant precursor. However, the endometriosis-ovarian cancer association is not widely accepted in the literature and additional studies are required to validate this association.Benign prostate hyperplasia (BPH) is one of the well-known urological neoplasms common in males with an increasing number of associated deaths in aging males. It causes uncomfortable urinary symptoms, including urine flow blockage, and may cause bladder, urinary tract or kidney problems. The histopathological and clinical knowledge regarding BPH is limited. In the present study, an in silico approach was applied that uses genome-scale microarray expression data to discover a wide range of protein-protein interactions in addition to focusing on specific genes responsible for BPH to develop prognostic biomarkers. Various genes that were differentially expressed in BPH were identified. Gene and functional annotation clusters were determined and an interaction analysis with disease phenotypes of BPH was performed, as well as an RNA tissue specificity analysis. Furthermore, a molecular docking study of certain short-listed gene biomarkers, namely anterior gradient 2 (AGR2; PDB ID 2LNT), steroid 5α-reductase 2 (PDB ID 6OQX), zinc finger protein 3 (PDB ID 5T00) and collagen type XII α1 chain (PDB ID 1U5M), was performed in order to identify alternative Chinese herbal agents for the treatment of BPH. Data from the present study revealed that AGR2 receptor (PDB ID 2LNT) and berberine (Huang Bo) form the most stable complex and therefore may be assessed in further pharmacological studies for the treatment of BPH.Severe cholestatic liver injury diseases, such as obstructive jaundice and the subsequent acute obstructive cholangitis, are induced by biliary tract occlusion. Heat shock protein 90 (HSP90) inhibitors have been demonstrated to be protective for various organs. The potential of HSP90 inhibitors in the treatment of cholestatic liver injury, however, remains unclear. In the present study, rat models of bile duct ligation (BDL) were established, the HSP90 inhibitor 17-dimethylamino-ethylamino-17-demethoxygeldanamycin (17-DMAG) was administered, and its ability to ameliorate the cholestasis-induced liver injuries was evaluated. In the BDL rat models and clinical samples, increased HSP90 expression was observed to be associated with cholestatic liver injury. Furthermore, 17-DMAG alleviated cholestasis-induced liver injury in the rat models, as revealed by the assessment of pathological changes and liver function. In addition, 17-DMAG protected hepatocytes against cholestatic injury in vitro. Further assays indicated that 17-DMAG administration prevented cholestasis-induced liver injury in the rats by decreasing the expression of interleukin (IL)-1β and IL-18.
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