Odontogenic carcinoma with dentinoid: case report and literature review of a rare entity.

BACKGROUND: Odontogenic carcinoma with dentinoid (OCD) is a rare and controversial entity, which has not yet been included in the current World Health Organization classification of odontogenic lesions. Owing to the small number of reported cases, the clinicopathological characteristics, biological behavior, prognosis, and appropriate treatment strategies for OCD remain to be defined. Herein, we present an additional case of OCD with a focus on the differential diagnosis and review of the pertinent literature, in order to enable better recognition by oral clinicians and pathologists and further characterization of this entity. CASE PRESENTATION: This paper reports a case of OCD in the posterior mandible of a 22-year-old female. Radiography showed a well-defined unilocular radiolucency with radiopaque materials. The intraoperative frozen section pathology gave a non-committed diagnosis of odontogenic neoplasm with uncertain malignant potential. Then a partial mandibulectomy with free iliac crest bone graft and titanium implants was performed. Microscopically, the tumor consisted of sheets, islands, and cords of round to polygonal epithelial cells associated with an abundant dentinoid matrix. Immunohistochemically, the tumor cells were diffusely positive for CK19, p63, and ß-catenin (cytoplasmic and nuclear). No rearrangement of the EWSR1 gene was detected. The final diagnosis was OCD. There has been no evidence of recurrence or metastasis for 58 months after surgery. We also provide a literature review of OCD cases, including one case previously reported as ghost cell odontogenic carcinoma from our hospital. CONCLUSIONS: OCD is a locally aggressive low grade malignancy without apparent metastatic potential. Wide surgical excision with clear margins and long-term period follow-up to identify any possible recurrence or metastases are recommended. Histopathological examination is essential to conclude the diagnosis. Special care must be taken to distinguish OCD from ghost cell odontogenic carcinoma and clear cell odontogenic carcinoma, as misdiagnosis might lead to unnecessary overtreatment. Study of additional cases is required to further characterize the clinicopathological features and clarify the nosologic status and biological behavior of this tumor.

Effects of cognitive behavioral therapy in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) causes airflow blockage and breathing-related issues. This chronic disease impacts people worldwide. Substantial evidence supports the use of cognitive behavioral therapy (CBT) to help patients with chronic illnesses cope with worrisome and painful symptoms. However, the impact of CBT on COPD outcomes is less understood. OBJECTIVE: In this study, we systematically summarized the effects of CBT on lung function, anxiety and depressive symptoms, and quality of life of patients with COPD. METHODS: Six English-language and four Chinese-language databases were systematically searched for relevant randomized controlled trials published through April 15, 2023. Studies in which CBT was the only difference in treatment administered to experimental and control groups were included in the review. The studies' risk of bias was evaluated using the Cochrane Criteria. RESULTS: Sixteen studies (1887 participants) were included. The meta-analysis showed that CBT improved the percent-predicted forced expiratory volume in 1 second (FEV1%), forced vital capacity (FVC), FEV1/FVC ratio, maximal voluntary ventilation, peak expiratory flow, treatment compliance, and World Health Organization abbreviated quality of life, Self-rating Anxiety and Depression Scale, and St George's Respiratory Questionnaire scores compared with the control (all p < .05). CONCLUSION: This review demonstrated that CBT improves the lung function, anxiety and depressive symptoms, treatment compliance, and quality of life of patients with COPD and can be used widely in the clinical treatment of this disease.

Extramammary Paget disease of the buccal mucosa in an elderly patient.

OBJECTIVE: To report a rare case of oral extramammary Paget disease in an elderly patient. BACKGROUND: Extramammary Paget disease is a rare cutaneous malignancy, and oral mucosa involvement is extremely rare. MATERIAL AND METHOD: The patient was a 72-year-old man with a whitish plaque and areas of erosion on the right buccal mucosa. RESULTS: An incisional biopsy was performed, and the diagnosis was extramammary Paget disease. CONCLUSION: Both clinicians and pathologists should be aware of this disease to avoid misdiagnoses with other oral benign or malignant lesions.

Identification of LIPH as an unfavorable biomarkers correlated with immune suppression or evasion in pancreatic cancer based on RNA-seq.

BACKGROUND: It is widely considered that pancreatic cancer (PC) is an immunosuppressive cancer. Immune-based therapies remain promising therapeutic strategies for PC. Overexpression of lipase H (LIPH) was reported to be related to immunity in cattle and has also been demonstrated to promote tumor progression in several tumors, but its role in pancreatic carcinogenesis remains unclear. Study on LIPH in PC might provide a new insight into the immunosuppression in PC. METHODS: The potential biological and clinical significance of LIPH was evaluated by bioinformatics analysis. We further investigated potential associations between the expression of LIPH and tumor immune infiltration using the CIBERSORT algorithm, the ESTIMAT algorithm, and single sample gene set enrichment analysis (ssGSEA). RESULTS: LIPH was significantly overexpressed in tumor tissues compared with normal tissues. LIPH overexpression correlated with tumor recurrence, advanced histologic grade, and poorer overall survival (OS). Four of the most common somatic mutation, including KRAS, TP53, CDKN2A, and SMAD4, in PC were all correlated with high LIPH expression. And high LIPH expression was significantly correlated with KRAS activation and SMAD4 inactivation. Besides, LIPH expression was involved in various biological pathways such as negative regulation of cell-cell adhesion, actin cytoskeleton, EMT, angiogenesis, and signaling by MST1. And LIPH overexpression caused high infiltration of TAMs, Treg cells, and Th2/Th1, but reduced the infiltration of CD8+ T cells and Th1 cells. CONCLUSIONS: Our findings demonstrated that LIPH correlated with immune suppression or evasion and may function as a novel unfavorable prognostic biomarker in PC.

KCa3.1 in diabetic kidney disease.

PURPOSE OF REVIEW: Diabetic kidney disease (DKD) is a significant health concern. Innovative strategies to prevent or limit the progression of DKD are urgently needed due to the limitation of existing treatments. KCa3.1, a potassium channel, is involved in a range of biological processes from cell survival to cell death. This review summarizes the current knowledge on the pathophysiological functions of the KCa3.1 channel, specifically its involvement in maintaining mitochondrial function. More specifically, the therapeutic potential of targeting KCa3.1 in DKD is systematically discussed in the review. RECENT FINDINGS: Mitochondrial dysfunction contributes to the development and progression of DKD. Accumulating evidence indicates that KCa3.1 dysregulation plays a crucial role in mitochondrial dysfunction, in addition to driving cellular activation, proliferation and inflammation. Recent studies demonstrate that KCa3.1 deficiency improves diabetes-induced mitochondrial dysfunction in DKD, which is attributed to modulation of mitochondrial quality control through mitigating the altered mitochondrial dynamics and restoring abnormal BNIP3-mediated mitophagy. SUMMARY: Based on its role in fibrosis, inflammation and mitochondrial dysfunction, pharmacological inhibition of KCa3.1 may offer a promising alternative for the treatment of DKD. Due to its safety profile in humans, the repurposing of senicapoc has the potential to expedite an urgently needed new drug in DKD.

Effects of Virtual Reality Rehabilitation Training on Cognitive Function and Activities of Daily Living of Patients With Poststroke Cognitive Impairment: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the effects of virtual reality (VR) rehabilitation training on the cognitive function and activities of daily living (ADL) of patients with poststroke cognitive impairment (PSCI). DATA SOURCES: Four Chinese databases and 6 English databases were systematically searched for studies published until August 31, 2021, by using Medical Subject Headings of the National Library of Medicine terms such as virtual reality, cognition disorders, cognitive dysfunction, and stroke and free terms such as virtual environment, VR, cognition impairment, cerebrovascular accident, and PSCI. STUDY SELECTION: Randomized controlled trials treating PSCI with VR training were included. The control groups received conventional treatments such as conventional rehabilitation training and drug therapy; the experimental groups received VR rehabilitation training. The outcome measures were cognitive function and ADL. DATA EXTRACTION: Two researchers independently extracted key information from eligible studies. The methodological quality of the studies was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions v5.1.0. Meta-analysis was performed using RevMan v5.4. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. DATA SYNTHESIS: Twenty-one studies (1149 participants) were included. Meta-analyses found that compared with the control group, VR rehabilitation training increased Mini-Mental State Examination, Montreal Cognitive Assessment, Loewenstein Occupational Therapy Cognitive Assessment, Rivermead Behavioral Memory Test Second Edition, Barthel Index, Modified Barthel Index, and FIM scores; event-related potential 300 (P300) amplitude; and the N-acetylaspartate/creatinine (Cr) ratio on proton magnetic resonance spectroscopy (1H-MRS) and reduced P300 latency; Trail Making Test scores; and the choline-containing compounds/Cr ratio on 1H-MRS (all P<.05). These results indicated that VR training improved cognitive function and ADL in PSCI. CONCLUSIONS: VR rehabilitation training promotes the rehabilitation of cognitive function and recovery of ADL in patients with PSCI and may be a good complementary approach to conventional cognitive interventions.

The effects of computer-assisted cognitive rehabilitation on cognitive impairment after stroke: A systematic review and meta-analysis.

OBJECTIVES: To determine the effectiveness of computer-assisted cognitive rehabilitation in improving cognitive function in patients with post-stroke cognitive impairment. BACKGROUND: In recent years, computer-assisted cognitive rehabilitation has been accepted as a good substitute or supplement for traditional cognitive rehabilitation. Some clinical randomised controlled trials have been carried out, but no relevant systematic evaluations have been performed. Therefore, we conducted a systematic review of studies involving computer-assisted cognitive rehabilitation to provide evidence-based data for its promotion and application. METHODS: Nine databases (Cochrane Library, PubMed, Web of Science, Embase, OVID, Wanfang Data, CNKI, VIP and SinoMed databases) were systematically searched. Randomised controlled trials that assessed computer-assisted cognitive rehabilitation for patients with post-stroke cognitive impairment were included. Two reviewers appraised the risks of bias through the Cochrane Collaboration's tool and performed the meta-analysis, including the assessment of heterogeneity. We follow the PRISMA 2020 guidelines. RESULTS: Thirty-two studies comprising 1837 participants were included. Compared with conventional therapy alone, the addition of computer-assisted cognitive rehabilitation significantly improved the global cognition of patients, evaluated using the Montreal cognitive assessment, mini-mental state examination and Loewenstein occupational therapy cognitive assessment (p < .01 for all tests). The therapy also significantly improved activities of daily living, assessed using the Barthel index, modified Barthel index and functional independence measure (p < .05 for all tests). CONCLUSION: Computer-assisted cognitive rehabilitation significantly improved the cognitive function and activities of daily living of patients with post-stroke cognitive impairment. RELEVANCE TO CLINICAL PRACTICE: Computer-assisted cognitive rehabilitation can be a valuable technique for cognitive rehabilitation after stroke. It is advantageous for improving patient cognition and restoring the overall functional state of patients. Moreover, the research findings can provide suggestions and inspiration for researchers to implement the proposal, which is conducive to the design of more rigorous and high-quality randomised controlled trials.

Therapeutic Potential of Photobiomodulation for Chronic Kidney Disease.

Chronic kidney disease (CKD) is a growing global public health problem. The implementation of evidence-based clinical practices only defers the development of kidney failure. Death, transplantation, or dialysis are the consequences of kidney failure, resulting in a significant burden on the health system. Hence, innovative therapeutic strategies are urgently needed due to the limitations of current interventions. Photobiomodulation (PBM), a form of non-thermal light therapy, effectively mitigates mitochondrial dysfunction, reactive oxidative stress, inflammation, and gut microbiota dysbiosis, all of which are inherent in CKD. Preliminary studies suggest the benefits of PBM in multiple diseases, including CKD. Hence, this review will provide a concise summary of the underlying action mechanisms of PBM and its potential therapeutic effects on CKD. Based on the findings, PBM may represent a novel, non-invasive and non-pharmacological therapy for CKD, although more studies are necessary before PBM can be widely recommended.

Understanding different cultural ecosystem services: An exploration of rural landscape preferences based on geographic and social media data.

Rural landscapes offer a variety of cultural ecosystem services (CESs). However, the relationship between rural landscape characteristics and different CESs is still poorly understood. Therefore, this study explored the rural areas of Huzhou city, China, as a case study to assess the main rural landscape characteristics of different CESs based on public preferences. First, 148 scenic spots were classified into four CESs (physical, experiential, intellectual and inspirational), and the public preferences for each scenic spot were determined by combining tourists' scores obtained from social media and government assessment scores. Then, the landscape characteristic indicators were constructed from the natural, infrastructural and sensory perspectives by combining geographic and social media data. Finally, the random forest model was used to evaluate the public preferences for rural landscape characteristics overall and for different CESs. The word frequency analysis showed that, in addition to the nature landscape, infrastructure and service had a strong influence on public preferences. The relationship with rural landscape characteristics varied across different CESs. For physical CESs, the convenience of infrastructure played a greater role than natural landscape characteristics. Experiential CESs, on the other hand, were affected by natural landscape characteristics themselves. Intellectual CESs had higher requirements for both infrastructure and nature. Inspirational CESs included sensory evaluation indicators, in addition to their focus on natural landscape characteristics and infrastructure, indicating that this category of CESs was more concerned with inner experience. The use of social media data has enriched the dimensions of sensory elements and provided new ideas and information supplements for comprehensively understanding different CESs, thus better supporting the management, planning and protection of rural landscapes.

Pasteurized Akkermansia muciniphila Reduces Fat Accumulation via nhr-49-Mediated Nuclear Hormone Signaling Pathway in Caenorhabditis elegans.

Pasteurized Akkermansia muciniphila (p-AKK) is related to lipid metabolism and helps control obesity. The main goal of this study was to investigate the role and mechanism of p-AKK in lipid metabolism using Caenorhabditis elegans. The results showed that p-AKK increased the healthy lifespan of nematodes and helped maintain exercise ability in aging, suggesting a potential increase in energy expenditure. The overall fat deposition and triglyceride level were significantly decreased and the p-AKK anti-oxidative stress helped to regulate fatty acid composition. Additionally, the transcriptome results showed that p-AKK increased the expression of lipo-hydrolase and fatty acid ß-oxidation-related genes, including lipl-4, nhr-49, acs-2 and acdh-8, while it decreased the expression of fat synthesis-related genes, including fat-7, elo-2 and men-1. These results partially explain the mechanisms underlying the fact that p-AKK decreases fat accumulation of C. elegans via nhr-49/acs-2-mediated signaling involved in fatty acid ß-oxidation and synthesis.

Warming needle moxibustion for Alzheimer's disease: A systematic review of randomized controlled trials.

OBJECTIVE: To systematically research the impact of warming needle moxibustion (WNM) for Alzheimer's Disease (AD). METHODS: Four Chinese databases and six English databases were systematically searched. Randomized controlled trials (RCTs) involving the use of WNM to intervene in AD patients were included. Data were extracted from the included studies and methodological quality was evaluated according to the Cochrane Handbook for Systematic Reviews of Intervention 5.1.0. Meta-analysis was performed using RevMan 5.4 software. RESULTS: 8 RCTs comprising 524 patients were included. Most studies had no significant bias. The study showed that WNM was more effective in the treatment of AD than acupuncture or pharmacotherapy. The findings were as follows: MMSE (MD = 1.01, 95%CI: 0.13, 1.90, P = 0.03) and CDR (MD = -0.73, 95%CI: -0.84, -0.61, P < 0.00001) for global cognitive function, ADL (MD = -1.84, 95%CI: -2.47, -1.22, P < 0.00001) for activities of daily living, Syndrome Differentiation Scale of Dementia (SDSD) (MD = -2.67, 95%CI: -3.62, -1.72, P < 0.00001), and the total effective rate of patients (OR = 3.20, 95%CI: 1.90 to 5.38, P < 0.0001). The differences in all indicators were statistically significant. CONCLUSION: WNM might have a significant effect on improving cognitive function and daily living ability, reducing the symptoms of AD, and increase the total effective rate. WNM is an effective non-pharmacological therapy for patients with AD.

Prognostic values and immune suppression of the S100A family in pancreatic cancer.

S100 calcium-binding protein A (S100A) family members regulate multiple biological functions related to pancreatic cancer (PC) progression and metastasis. However, the prognostic and oncologic values of S100A family have not been systematically investigated in PC. In the present study, the mRNA expression and potential functions of S100A family were investigated by bioinformatic analysis. Our results demonstrated that overexpression of S100A2, S100A6, S100A10, S100A11, S100A14 and S100A16 was significantly associated with higher T stage, advanced histologic grade and worse prognosis in PC. Besides, one CpG of S100A2, three CpG of S100A6, four CpG of S100A10, four CpG of S100A11, two CpG of S100A14 and five CpG of S100A16 were negatively associated with corresponding S100A family members expression and positively associated with overall survival (OS). The signature based on four CpGs showed good prediction ability of OS. Besides, S100A2 overexpression took part in the regulation of mitotic cell cycle, ECM-receptor interaction and HIF-1α transcription factor network. Overexpression of S100A6, S100A10, S100A11, S100A14 and S100A16 may impair the infiltration and cytolytic activity of CD8+ T cells through focal adhesion-Ras-stimulating signalling pathway in PC. Overall, this study explores the multiple prognostic values and oncologic functions of the S100A family in PC.

Inactivation of homeodomain-interacting protein kinase 2 promotes oral squamous cell carcinoma metastasis through inhibition of P53-dependent E-cadherin expression.

Homeodomain-interacting protein kinase 2 (HIPK2), a well-known tumor suppressor, shows contradictory expression patterns in different cancers. This study was undertaken to clarify HIPK2 expression in oral squamous cell carcinoma (OSCC) and to reveal the potential mechanism of HIPK2 involvement in OSCC metastasis. Two hundred and four OSCC tissues, together with paired adjacent normal epithelia, dysplastic epithelia, and lymph node metastasis specimens, were collected to profile HIPK2 expression by immunohistochemical staining. High throughput RNA-sequencing was used to detect the dysregulated signaling pathways in HIPK2-deficient OSCC cells. Transwell assay and lymphatic metastatic orthotopic mouse model assay were undertaken to identify the effect of HIPK2 on tumor invasion. Western blotting and luciferase reporter assay were used to examine the HIPK2/P53/E-cadherin axis in OSCC. Nuclear delocalization of HIPK2 was observed during oral epithelial cancerization progression and was associated with cervical lymph node metastasis and poor outcome. Depletion of HIPK2 promoted tumor cell invasion in vitro and facilitated cervical lymph node metastasis in vivo. According to mRNA-sequencing, pathways closely related to tumor invasion were notably activated. Homeodomain-interacting protein kinase 2 was found to trigger E-cadherin expression by mediating P53, which directly targets the CDH1 (coding E-cadherin) promoter. Restoring P53 expression rescued the E-cadherin suppression induced by HIPK2 deficiency, whereas rescued cytoplasmic HIPK2 expression had no influence on the expression of E-cadherin and cell mobility. Together, nuclear delocalization of HIPK2 might serve as a valuable negative biomarker for poor prognosis of OSCC and lymph node metastasis. The depletion of HIPK2 expression promoted OSCC metastasis by suppressing the P53/E-cadherin axis, which might be a promising target for anticancer therapies.

RIPK3 blockade attenuates kidney fibrosis in a folic acid model of renal injury.

Renal fibrosis is common to all forms of progressive kidney disease. However, current therapies to limit renal fibrosis are largely ineffective. Phosphorylation of receptor-interacting serine/threonine-protein kinase (RIPK) 3 has been recently suggested to be a key regulator of the pyrin domain containing 3 (NLRP3) inflammasome, which provides new insights into mechanisms of chronic kidney disease (CKD). However, the specific effect of RIPK3 on renal cortical fibrosis has not been fully understood. To study the function of RIPK3, both genetic ablation and pharmacological inhibition of RIPK3 (dabrafenib) were used in the study. Our studies identify that RIPK3 promotes renal fibrosis via the activation of the NLRP3 inflammasome in a mouse model of folic acid-induced nephropathy. Both interventional strategies decreased the renal fibrotic response, and beneficial effects converged on the NLRP3 inflammasome. This study demonstrates a role for RIPK3 as the mediator of renal fibrosis via the upregulation of inflammasome activation. Dabrafenib, as an inhibitor of RIPK3, may be an effective treatment to limit the progression of the tubulointerstitial fibrosis.

Clinicopathological and genetic characteristics of diffuse large B-cell lymphoma of the oropharyngeal and maxillofacial region.

OBJECTIVES: The study was aimed to analyze the clinicopathological and molecular pathological features of diffuse large B-cell lymphoma (DLBCL) in the oropharyngeal and maxillofacial region. SUBJECTS AND METHODS: A retrospective review was performed with 36 patients who were diagnosed with primary DLBCL of the oropharyngeal and maxillofacial region from 2009 to 2017 in the Department of Pathology at the Hospital of Stomatology, Wuhan University. Immunohistochemistry and fluorescence in situ hybridization were performed. RESULTS: Gene rearrangements of BCL2, BCL6, and MYC were observed in 5.6%, 33.3%, and 22.2%, respectively, including two double-hit and one triple-hit DLBCL (8.3%). There was a significant correlation between MYC protein expression and gene translocation (rs = 0.679, p < .001). However, 25% of cases with MYC rearrangement showed low MYC protein expression. In univariate analysis, MYC protein expression, BCL2 rearrangement, MYC rearrangement, and double/triple-hit DLBCL were associated with shorter overall survival, whereas only MYC protein expression was an independent prognostic value in multivariate model. CONCLUSIONS: MYC protein expression was an essential prognostic marker of DLBCL in the oropharyngeal and maxillofacial region. Notably, immunohistochemical staining of MYC, BCL2, and BCL6 could not predict their gene rearrangements, although MYC protein expression was correlated with gene translocation.

Mesenchymal Stem Cell-Derived Extracellular Vesicles to the Rescue of Renal Injury.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are rising in global prevalence and cause significant morbidity for patients. Current treatments are limited to slowing instead of stabilising or reversing disease progression. In this review, we describe mesenchymal stem cells (MSCs) and their constituents, extracellular vesicles (EVs) as being a novel therapeutic for CKD. MSC-derived EVs (MSC-EVs) are membrane-enclosed particles, including exosomes, which carry genetic information that mimics the phenotype of their cell of origin. MSC-EVs deliver their cargo of mRNA, miRNA, cytokines, and growth factors to target cells as a form of paracrine communication. This genetically reprograms pathophysiological pathways, which are upregulated in renal failure. Since the method of exosome preparation significantly affects the quality and function of MSC-exosomes, this review compares the methodologies for isolating exosomes from MSCs and their role in tissue regeneration. More specifically, it summarises the therapeutic efficacy of MSC-EVs in 60 preclinical animal models of AKI and CKD and the cargo of biomolecules they deliver. MSC-EVs promote tubular proliferation and angiogenesis, and inhibit apoptosis, oxidative stress, inflammation, the epithelial-to-mesenchymal transition, and fibrosis, to alleviate AKI and CKD. By reprogramming these pathophysiological pathways, MSC-EVs can slow or even reverse the progression of AKI to CKD, and therefore offer potential to transform clinical practice.

The Mitochondrial Kinase PINK1 in Diabetic Kidney Disease.

Mitochondria are critical organelles that play a key role in cellular metabolism, survival, and homeostasis. Mitochondrial dysfunction has been implicated in the pathogenesis of diabetic kidney disease. The function of mitochondria is critically regulated by several mitochondrial protein kinases, including the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1). The focus of PINK1 research has been centered on neuronal diseases. Recent studies have revealed a close link between PINK1 and many other diseases including kidney diseases. This review will provide a concise summary of PINK1 and its regulation of mitochondrial function in health and disease. The physiological role of PINK1 in the major cells involved in diabetic kidney disease including proximal tubular cells and podocytes will also be summarized. Collectively, these studies suggested that targeting PINK1 may offer a promising alternative for the treatment of diabetic kidney disease.

PTBP3 promotes migration of non-small cell lung cancer through regulating E-cadherin in EMT signaling pathway.

BACKGROUND: Human polypyrimidine tract binding protein 3 (PTBP3), which belongs to the PTB family, demonstrate a significant tumorigenic capability in a variety of malignancies. However, the correlation between PTBP3 expression and pathogenesis of non-small cell lung cancer (NSCLC) remains little known. The design of the study attempts to examine the role of PTBP3 in the pathogenesis and prognosis of NSCLC. METHODS: Our study conducted an investigation on the PTBP3 expression in human NSCLC tissues and a comprehensive analysis of the associations between three factors, involving the PTBP3 expression, clinicopathological features, and patient's survival. Additionally, we also explored the role of PTBP3 expression in the proliferation and invasion of cancer cells. RESULTS: The mining of The Cancer Genome Atlas (TCGA) database, western blotting and immunohistochemistry analyses showed significantly up-regulation of PTBP3 in NSCLC tissues than in normal tissues. Although overexpress or knockdown PTBP3 expression had no significant effect on proliferation of selected cell line, it could promotes migration of NSCLC cells via regulating E-cadherin in epithelial-mesenchymal transition (EMT) signaling pathway. Moreover, in the univariate analysis, the PTBP3-high is markedly related to poor overall survival results where hazard ratio (HR): 1.55; 95% confidence interval (95% CI): 1.87-2.01; p = 0.0001. Also, according to the multivariate analysis, an independent prognostic factor among NSCLC patients is the PTBP3 with an HR of 1.42 (CI: 1.09-1.9; p = 0.011). To explore potential signaling pathways, we used the TCGA dataset and performed Gene Set Enrichment Analysis (GSEA). Moreover, its expression in NSCLC was related to Tumor differentiation, lymph node metastasis, distant metastasis status and poor prognosis. Beside, by changing the expression of PTBP3 in selected cell lines, we found that overexpress or knockdown PTBP3 expression had no significant effect on proliferation, however it regulated migration possibly by EMT signaling. CONCLUSIONS: Collectively, our findings suggested that PTBP3 contributed to the progression of NSCLC and might serve as a potential target for anti-cancer therapy.

Uranium Isotope Fractionation (238U/235U) during U(VI) Uptake by Freshwater Plankton.

Uranium contamination in the environment is a serious public health concern. Biotic U(VI) reduction and nonreductive U(VI) uptake by microorganisms (e.g., U(VI) biosorption by cyanobacteria) are effective U remediation techniques. Variations of 238U/235U have been extensively explored to track biotic U(VI) reduction in laboratory experiments and field applications. However, U isotope fractionation during nonreductive U(VI) uptake by microorganisms is poorly constrained. To investigate U isotope fractionation in this process, we cultured freshwater plankton in the presence of U(VI) and measured 238U/235U in the culture media and biomass. We found that nonreductive U(VI) uptake by freshwater plankton fractionated U isotopes in the opposite direction compared to biotic U(VI) reduction. δ238U values in freshwater plankton were consistently ∼0.23 ± 0.06‰ lighter than those in dissolved U in the culture medium at various fractions of U removal (12-30%), consistent with equilibrium isotope fractionation in a closed system. The equilibrium isotope fractionation observed in our experiments possibly results from changes in coordination geometry between dissolved U(VI) in the culture media and adsorbed U(VI) on cell surfaces. Our experimental results highlight the need to consider U isotope fractionation during nonredox U(VI) uptake by microorganisms and organic matter when applying variations of 238U/235U to track biogeochemical processes and evaluate U remediation.

Metformin attenuates folic-acid induced renal fibrosis in mice.

Progressive tubulointerstitial fibrosis has been recognized as a common pathological process that leads to the progression of all chronic kidney disease (CKD). Innovative strategies are needed to both prevent and treat CKD. Inflammatory and fibrotic signaling pathways play central roles in the progression of CKD regardless of aetiology. Hence, targeting inflammatory and fibrotic responses holds promise to limit renal fibrosis. Metformin has been the most prescribed glucose-lowering medicine worldwide, and its potential for many other therapeutic applications is also being explored intensively. Increasing evidence indicates metformin may limit renal fibrosis. However, the exact mechanisms whereby metformin limits renal injury are not fully understood. The anti-fibrotic effects of metformin, independent of improved glycaemic control was examined in a folic acid-induced mouse model of nephropathy for 14 days. Human proximal tubular cells (HK2 cells) exposed to TGF-ß1 were used in in vitro models to examine mechanistic pathways. Folic acid induced nephropathy was associated with the overexpression of inflammatory markers MCP-1, F4/80, type IV collagen, fibronectin and TGF-ß1 compared to control groups, which were partially attenuated by metformin treatment. In vitro studies confirmed that metformin inhibited TGF-ß1 induced inflammatory and fibrotic responses through Smad3, ERK1/2, and P38 pathways in human renal proximal tubular cells. These results suggest that metoformin attenuates folic acid-induced renal interstitial fibrogenesis through TGF-ß1 signaling pathways.