Effects of silencing NLRP3 gene on proliferation of psoriasis-like HaCaT cells and expressions of cytokines.

We aimed to explore the effects of silencing NOD-like receptor protein 3 (NLRP3) on proliferation of psoriasis-like HaCaT cells and expressions of cytokines. HaCaT cells were treated with human keratinocyte growth factor (KGF) and were divided into KGF group, negative control group, NLRP3-RNAi group and control group. Cells proliferation was detected by CCK8, cell clone formation rate was detected by clone formation assay, distribution of cells cycle was detected by flow cytometry, expressions of cyclin B1 (Cyclin B1), cyclin-dependent kinase 2 (CDK2), Ki67 and proliferating cell nuclear antigen (PCNA) proteins were detected by Western blot, and levels of interleukin (IL)-17, IL-23, IL-6 and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay. Compared with control group, expressions of NLRP3 mRNA and protein, proliferation rate and clonal formation rate were increased in KGF group, percentage of cells in G0/G1 phase was decreased, percentage of cells in S phase was increased, expressions of Cyclin B1, CDK2, Ki67 and PCNA proteins were increased, and levels of IL-17, IL-23, IL-6 and TNF-α were increased. Compared with negative control group, expressions of NLRP3 mRNA and protein, proliferation rate and clonal formation rate were decreased in NLRP3-RNAi group, percentage of cells in G0/G1 phase was increased, percentage of cells in S phase was decreased, expressions of Cyclin B1, CDK2, Ki67 and PCNA proteins were decreased, and levels of IL-17, IL-23, IL-6 and TNF-α were decreased. Silencing NLRP3 gene can inhibit the proliferation of psoriasis-like HaCaT cells, arrest cell cycle, inhibit the expressions of cell proliferation-related proteins and reduce levels of pro-inflammatory factors.

A novel m7G regulator-based methylation patterns in head and neck squamous cell carcinoma.

Abnormal RNA N7-methylguanosine (m7G) modification is known to contribute to effects on tumor occurrence and development. Nevertheless, the mechanisms of its function in immunoregulation, tumor microenvironment (TME) modulation, and tumor promotion remain largely unknown. A series of computer-aided bioinformatic analyses were conducted based on transcriptomic, single-cell sequence, and spatial transcriptomic data to determine the m7G modification patterns in head and neck squamous cell carcinoma (HNSCC). Consensus clustering approach was employed according to the expressions of 33 m7G regulators. ESTIMATE, CIBERSORT, and single sample gene set enrichment analysis algorithms were adopted to investigate the immune cell infiltration features. A prognostic model named m7Gscore was established. Seurat, SingleR, and Monocle2 were used to analyze the single-cell sequence profiling. STUtility was used to integrate multiple spatial transcriptomic datasets. Quantitative reverse transcription polymerase chain reaction, transwell, and wound-healing assay were performed to verify the oncogenes. Here, three different m7G modification patterns were highlighted in HNSCC patients, which were also related to various clinical manifestations and three representative immunophenotypes: immune-excluded, immune-desert, and inflamed, separately. Patients with lower m7Gscore were highlighted by higher immune cell infiltrations, better overall survival rates, lesser tumor mutation burden (TMB), lower sensitivities to target inhibitors therapies, and better immunotherapeutic response. Moreover, DCPS, EIF4E, EIF4E2, LSM1, NCBP2, NUDT1, and NUDT5 were identified to play critical roles in T-cell differentiation. Knockdown of LSM1/NUDT5 could restrain the malignancy of HNSCC cells. Collectively, quantitative assessment of m7G modification patterns in individual HNSCC patients could contribute to identifying more efficient immunotherapeutic approaches and improve the clinical outcome of HNSCC.

In-silico target prediction by ensemble chemogenomic model based on multi-scale information of chemical structures and protein sequences.

Identification and validation of bioactive small-molecule targets is a significant challenge in drug discovery. In recent years, various in-silico approaches have been proposed to expedite time- and resource-consuming experiments for target detection. Herein, we developed several chemogenomic models for target prediction based on multi-scale information of chemical structures and protein sequences. By combining the information of a compound with multiple protein targets together and putting these compound-target pairs into a well-established model, the scores to indicate whether there are interactions between compounds and targets can be derived, and thus a target prediction task can be completed by sorting the outputted scores. To improve the prediction performance, we constructed several chemogenomic models using multi-scale information of chemical structures and protein sequences, and the ensemble model with the best performance was used as our final model. The model was validated by various strategies and external datasets and the promising target prediction capability of the model, i.e., the fraction of known targets identified in the top-k (1 to 10) list of the potential target candidates suggested by the model, was confirmed. Compared with multiple state-of-art target prediction methods, our model showed equivalent or better predictive ability in terms of the top-k predictions. It is expected that our method can be utilized as a powerful computational tool to narrow down the potential targets for experimental testing.

Effectiveness and safety of auricular acupuncture for psoriasis: A protocol for systematic review and meta-analysis.

BACKGROUND: Psoriasis is a chronic, immune-mediated, polygenic skin disease that is common in clinical practice and often develops on the extremities, back, and scalp of patients. In that psoriasis lesions are stubborn and prone to recurrence, it has a serious impact on patients' quality of life and is detrimental to their physical and psychological health. Auricular acupuncture is one of the traditional Chinese medical treatments, which has the advantages of low adverse effects and simple operation and has been widely used in clinical practice with good efficacy. However, there has been no systematic evaluation of auricular acupuncture in the treatment of psoriasis. This protocol aims to evaluate the effectiveness and safety of auricular acupuncture in patients with psoriasis. METHODS: We will search the following 8 databases including PubMed, MEDLINE, EMBASE, Cochrane Library, CNKI, Wan Fang, VIP, and CBM databases for randomized controlled trials of auricular acupuncture treated psoriasis from their inception to 10 October 2022. We will analyze the data meeting the inclusion criteria with the RevMan V.5.4 software. Two authors will assess the quality of the study with the Cochrane systematic evaluation tool. Treatment effectiveness and the psoriasis area and severity index are defined as the main outcomes, and the additional outcomes include itchy, dermatology life quality index, relapse rate, and adverse events. RESULTS: This study will review and evaluate the available evidence on the effectiveness and safety of auricular acupuncture for psoriasis. CONCLUSIONS: The results of this study will provide evidence for the effectiveness and safety of treating psoriasis, providing clinicians and patients with appropriate treatment options for this disease.

Differences in the Distribution of Species, Carbapenemases, Sequence Types, Antimicrobial Heteroresistance and Mortality Rates Between Pediatric and Adult Carbapenemase-Producing Enterobacterales in Bloodstream Infections.

The dissemination of carbapenemase-producing Enterobacterales (CPE) is worrisome given their scarce treatment options. CPE bloodstream infections (BSIs) had a high mortality rate in adults, and there was little data on pediatric CPE-BSIs around the world. We comprehensively explored the differences in the clinical and microbiological characteristics between pediatric and adult CPE-BSIs. Forty-eight pediatric and 78 adult CPE-BSIs cases were collected. All-cause 30 day-mortality in children with CPE-BSIs (14.6%, 7/48) was significantly lower than that in adult patients (42.3%, 33/78, p = 0.001). The subgroup in adults empirically treated with tigecycline as an active drug displayed a significantly higher 30-days crude mortality (63.3%, 19/30) than the subgroup treated without tigecycline (29.2%, 14/48, p = 0.003). K. pneumoniae was the most prevalent species in both the pediatric (45.8%, 22/48) and adult populations (64.1%, 50/78), with discrepant carbapenemase genes in each population: 95.4% (21/22) of the pediatric K. pneumoniae isolates carried bla NDM, while 82.0% (41/50) of the adult strains harbored bla KPC. The ratio of E. coli in children (37.5%) was significantly higher than that in adults (12.8%, p = 0.002). In both populations, the majority of E. coli expressed bla NDM, particularly bla NDM-5. With statistical significance, bla NDM was much more common in children (95.8%, 46/48) than in adults (34.6%, 27/78). The rate of multiple-heteroresistance phenotypes in children was as high as 87.5%, which was much lower in adults (57.1%). Agar dilution checkboard experiment against one pediatric carbapenemase-producing E. coli isolates showed that the combination of amikacin and fosfomycin yielded an additive effect. Overall, K. pneumoniae was the most common CPE-BSIs pathogen in both populations, with NDM-producing K. pneumoniae and KPC-producing ST11 K. pneumoniae being the most prevalent species in children and adults, respectively. E. coli was more prevalent in children than in adults, yet bla NDM-5 was the most common carbapenem-resistant mechanism in E. coli in both populations. The wide range of multiple-heteroresistance combination traits found in different pathogen species from different host populations should provide a good foundation for future combination therapy design. Further investigations from more CPE isolates of various species are needed to evaluate the possible in vitro partial synergy of the amikacin and fosfomycin combination.

MicroRNA-31: a pivotal oncogenic factor in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) continuously constitutes a major challenge for treatment and prognosis due to approximately half of treated OSCC patients dying from locoregional recurrences and distant metastases. MicroRNA-31 (miR-31), an early mammalian miRNA identified, has been gaining importance in the field of OSCC research in recent years. This comprehensive review was conducted for the first time to summarize the current evidence on the association between miR-31 and OSCC. The vast majority of relevant studies (20/21, 95%) demonstrated that miR-31 was an oncogenic factor in the tumorigenesis and progression of OSCC. miR-31 expression is significantly upregulated in plasma, saliva, and tumor tissue of OSCC. miR-31 played an essential role in OSCC development by constituting a complex network with its targeted genes (e.g. RhoA, FIH, ACOX1, VEGF, SIRT3, LATS2, KANK1, and NUMB) and the signaling cascades (e.g. EGF-AKT signaling axis, ERK-MMP9 cascade, Hippo pathway, Wnt signaling, and MCT1/MCT4 regulatory cascade). This review highlights that miR-31 might function as a potential diagnostic, prognostic, and predictive biomarker for OSCC. Further studies are still warranted to better illuminate the clinicopathological features and the molecular mechanisms of miR-31-mediated OSCC development.

Risk of osteoporosis and fracture after hysterectomies without oophorectomies: a systematic review and pooled analysis.

The present study provides evidence that women who underwent hysterectomy without oophorectomies are at a higher risk of osteoporosis and bone fractures than the general population. Early interventions for these susceptible women may help to delay or reduce the risk of osteoporosis and bone fractures. INTRODUCTION: Mounting studies have shown that patients with hysterectomy are at high risk of developing osteoporosis or bone fractures, but the evidence from all the relevant studies has not been previously synthesized. The present study aims to investigate whether women with hysterectomy without oophorectomies have a prominently higher prevalence of osteoporosis or fractures than healthy subjects. METHODS: Four electronic databases were systematically searched to identify the eligible studies. The combined effect was assessed by calculating the relative risk (RR) with a 95% confidence interval (CI). More methodologies for this study were available in the PROSPERO (ID: CRD42021227255). RESULTS: Finally, three observational studies offering osteoporosis cases and two retrospective studies reporting fracture cases were included. One eligible study has provided independent data from three groups of fractures. Synthetic results revealed that hysterectomy without oophorectomies was significantly associated with an increased risk of osteoporosis as compared to the general population (combined RR from three studies = 1.47, 95%CI 1.253 to 1.725, P < 0.001; heterogeneity, I2 = 76.2%, P = 0.015). Consistently, the prevalence of fractures was also significantly higher in patients with hysterectomy without oophorectomies than in healthy controls (pooled RR from four studies = 2.333, 95%CI: 1.314 to 4.144, P = 0.004; heterogeneity, I2 = 92.3%, P < 0.001). CONCLUSIONS: This is the first study to quantify the association between hysterectomy without oophorectomies and osteoporosis/fracture risk through a meta-analysis and has subsequently confirmed its positive relationship. Additional large-sample rigorously prospective cohorts are still warranted to validate the present evidence.

TCM Treatment and Drug Co-Occurrence Analysis of Psoriasis.

Psoriasis is a long-term immune-mediated disease. Patients with a long history and slow progress are more common, and its treatment is difficult. This study proposes to use traditional Chinese medicine to treat psoriasis. Through the follow-up of all participants for 12 and 24 weeks, a large number of comparative experiments effectively verify the effectiveness of the method proposed in this study. The research results of this study can provide some reference ideas for follow-up research.

A dual-quenched ECL immunosensor for ultrasensitive detection of retinol binding protein 4 based on luminol@AuPt/ZIF-67 and MnO2@CNTs.

BACKGROUND: Retinol binding protein 4 (RBP4) has been regarded as an important serological biomarker for type 2 diabetes mellitus (T2DM). Hence, the construction of a highly sensitive detection method for RBP4 is the key to early prevention and multidisciplinary intervention of T2DM. In this work, a dual-quenched electrochemiluminescence (ECL) immunosensor has been fabricated for ultrasensitive detection of RBP4 by combining zeolitic imidazolate framework-67/AuPt-supported luminol (luminol@AuPt/ZIF-67) with MnO2 nanosheets-grown on carbon nanotubes (MnO2@CNTs). RESULTS: AuPt/ZIF-67 hybrids with high-efficiency peroxidase-like activity could provide multipoint binding sites for luminol and antibodies and significantly boost the amplified initial signal of the ECL immunosensor. Upon glutathione/H2O2 coreactants system, MnO2@CNTs composites could quench the initial signal by inhibiting mimic peroxidase activity of luminol@AuPt/ZIF-67. Moreover, the absorption spectrum of the MnO2@CNTs composites completely overlaps with the emission spectrum of luminol, which can further reduce initial signal by ECL resonance energy transfer (ECL-RET). CONCLUSIONS: Benefiting from the above-mentioned properties, the designed immunoassay sensitivity exhibited excellent sensitivity and relative stability for RBP4 detection range from 0.0001 to 100 ng mL-1 with a low detection limit of 43 fg mL-1. Therefore, our ECL immunosensor provides an alternative assaying strategy for early diagnosis of T2DM.

One-Pot Identification of BCR/ABLp210 Transcript Isoforms Based on Nanocluster Beacon.

The BCR/ABLp210 fusion gene is a classic biomarker of chronic myeloid leukemia, which can be divided into e13a2 and e14a2 isoforms according to different breakpoints. These two isoforms showed distinct differences in clinical manifestation, treatment effect, and prognosis risk. Herein, a strategy based on nanocluster beacon (NCB) fluorescence was developed to identify the e13a2 and e14a2 isoforms in one-pot. Because the fluorescence of AgNCs can be activated when they are placed in proximity to the corresponding enhancer sequences, thymine-rich (T-rich) or guanine-rich (G-rich). In this work, we explored an ideal DNA-AgNCs template as an excellent molecular reporter with a high signal-to-noise ratio. After recognition with the corresponding isoforms, the AgNCs can be pulled closer to the T-rich or G-rich sequences to form a three-way junction structure and generate fluorescence with corresponding wavelengths. Therefore, by distinguishing the corresponding wavelengths of AgNCs, we successfully identified two isoforms in one tube with the limitation of 16 pM for e13a2 and 9 pM for e14a2. Moreover, this strategy also realized isoform identification in leukemia cells and newly diagnosed CML patients within 40 min, which provides a powerful tool to distinguish fusion gene subtypes at the same time.

Nonalcoholic fatty liver disease and risk of prostatic diseases: Roles of insulin resistance.

Nonalcoholic fatty liver disease (NAFLD), the liver component of metabolic syndrome, is considered to be associated with high risk of prostatic diseases but a systematic review has not been conducted. Under a comprehensive review of the eligible clinical studies, a potential positive association between NAFLD and benign prostatic hyperplasia/prostate cancer (BPH/PCa) has been postulated. Insulin resistance and metabolic aberrations are considered to be the potential mechanism for such association. However, the relationship between NAFLD and other prostatic diseases, that is, prostatic inflammation and lower urinary tract symptoms, seems vague due to limited relevant studies in the literatures. The present review highlights that clinicians should be conscious of the detrimental effect of NAFLD on the development of BPH and PCa.

Is there an association between peptic ulcer disease and osteoporosis: a systematic review and cumulative analysis.

BACKGROUND: Mounting studies have emerged indicating that patients with peptic ulcer disease (PUD) are at a high risk of developing osteoporosis, but the evidence has not been previously synthesized. The present study aims to examine whether patients with PUD have a significantly higher prevalence of osteoporosis than the healthy normal subjects. METHODS: Four electronic databases were systematically searched for eligible studies up to February 2020. The association between PUD and osteoporosis was evaluated by calculating the relative risk (RR) with a 95% confidence interval (CI). RESULTS: Six observational studies were finally included, enrolling a total of 216 122 individuals. Synthetic results from the six included studies providing the number of cases for both sexes demonstrated that PUD was significantly associated with an increased risk of osteoporosis (95% CI, 1.37-1.89; P < 0.001). In line with this finding, the combined effect from the three studies independently reporting the male subjects also yielded to a positive relationship between PUD and osteoporosis (RR = 2.08; 95% CI,1.10-3.93; P = 0.023). However, when restricted to female participants, pooled results indicated that women patients with PUD would not suffer significantly more risk of osteoporosis than the general women population (RR = 1.36; 95% CI, 0.84-2.21, P = 0.212). CONCLUSIONS: This is the first study for quantifying the positive association between PUD and the risk of osteoporosis by conducting a meta-analysis. In clinical practice, assessment of the bone mineral density and antiosteoporosis treatments are recommended for those potential patients with PUD.

Efficacy and safety of fire needle therapy for blood stasis syndrome of plaque psoriasis: protocol for a randomized, single-blind, multicenter clinical trial.

BACKGROUND: Fire needle therapy is a characteristic treatment in traditional Chinese medicine (TCM). An increasing number of studies have indicated that fire needle treatment for psoriasis provides satisfactory results with few side effects and a low recurrence rate. We herein describe the protocol for a multicenter, randomized, single-blind, placebo-controlled trial that will provide high-quality evidence on the efficacy and safety of fire needle therapy for plaque psoriasis. METHODS: Ninety-two patients with blood stasis syndrome (BSS) of plaque psoriasis will be enrolled and randomly assigned to receive fire needle therapy (intervention group) or fire needle control therapy (control group) once a week for 4 weeks. The Psoriasis Area and Severity Index (PASI) score will serve as the major efficacy index, while the body surface area (BSA), Physician Global Assessment (PGA) score, Dermatology Life Quality Index (DLQI) score, patient-reported quality of life (PRQoL), visual analog scale (VAS) score for itching, TCM symptom score, and relapse rate will be assessed as secondary outcomes. The PASI score, BSA, PGA score, and VAS score for itching will be evaluated at baseline and during the 4-week treatment and follow-up periods. DLQI score, PRQoL, and TCM symptom score will be assessed at baseline and during the treatment period. Recurrence will be evaluated during the follow-up period. Safety assessments include vital sign monitoring, routine blood tests, blood biochemistry, routine urine tests, pregnancy tests, physical examinations, and adverse-event recording. SAS software will be used for data analysis. The data network platform will be designed by the data management center of Nanjing Ningqi Medical Technology Co., Ltd. DISCUSSION: It is believed that fire needle therapy can activate the meridians, promote blood circulation, and regulate skin immunity. BSS of plaque psoriasis is related to not only immune dysfunction but also poor or stagnant blood flow. We anticipate that the results of the trial described in this protocol will provide strong evidence for the safety and efficacy of fire needle therapy for BSS of plaque psoriasis. TRIAL REGISTRATION: Clinicaltrials.gov NCT03953885 . Registered on May 15, 2019. Name: Fire Needle Therapy on Plaque Psoriasis with Blood Stasis Syndrome.

Effects of moving cupping therapy for plaque psoriasis: study protocol for a randomized multicenter clinical trial.

BACKGROUND: It is difficult to achieve a balance among safety, efficacy, and cost for the clinical treatment of plaque psoriasis. The current treatment of psoriasis often involves comprehensive therapy such as topical plasters, internal medicine, and phototherapy, which are expensive, and some of the drugs have serious side effects. Moving cupping is a type of cupping that has been used clinically for thousands of years in China. It has the advantage of being inexpensive and easy to perform. Therefore, it is widely used in public hospitals in China for psoriasis treatment. However, a comprehensive evaluation of the current clinical evidence of its efficacy is lacking. In this study, we aimed to evaluate the efficacy and safety of moving cupping to treat plaque psoriasis. METHODS: A multicenter, two-arm parallel group, single-blind, randomized, controlled trial will be conducted at six hospitals in China between August 1, 2019 and December 31, 2021. A total of 122 adult patients (aged 18-65 years) who meet the inclusion criteria are being recruited. Participants will receive either basic treatment combined with moving cupping therapy or basic treatment combined with moving cupping placebo. The treatment cycle will be 4 weeks, and the efficacy of treatment will be assessed weekly by the Psoriasis Area and Severity Index during the treatment period and follow-up visits at weeks 6 and 8. The body surface area, physician's global assessment, Dermatology Life Quality Index, patient-reported quality of life, visual analog scale, Traditional Chinese Medication syndrome scoring scale, combined medication, and adverse events will also be recorded and compared to the relative baseline values. DISCUSSION: The findings of this trial may lead to better decisions regarding the treatment of plaque psoriasis. If the trial outcomes are considered favorable, this ancient Chinese medical therapy may be worthy of widespread use because of its convenience and low cost. TRIAL REGISTRATION: This study was registered on May 15,2019 at ClinicalTrials.gov with the identifier number NCT03952676.

Oral Taodan granules for mild-to-moderate psoriasis vulgaris: protocol for a randomized, double-blind, multicenter clinical trial.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease with high recurrence rates and increasing incidence. Patients require long-term medication to reduce symptoms and prevent disease progression. Therefore, the development of treatments with high efficiency and low rate of adverse events is of utmost importance. Traditional Chinese medicine (TCM) plays an outstanding role in reducing disease symptoms and improving quality of life. The aim of this trial is to clarify the treatment efficacy, safety, and control of disease recurrence in patients with psoriasis with blood-stasis syndrome treated with Taodan granules (TDKL). METHODS: This trial is a five-center, randomized, double-blind, placebo-controlled study planned to transpire between September 1, 2019, and December 31, 2021. A sample size of 216 participants (108 per group) with mild-to-moderate psoriasis will be randomly assigned to receive TDKL or placebo twice per day, 7 days per week, for 8 weeks. The study duration will be 17 weeks, including a 1-week screening period, 8 weeks of intervention, and another 8 weeks of follow-up. The primary outcomes are improvement in the Psoriasis Area and Severity Index score and recurrence rate after 8 weeks of treatment. Secondary outcomes include body surface area affected and the scores for the Physician Global Assessment, Dermatology Life Quality Index, pain-related quality of life, pain on the visual analogue scale, and TCM syndromes. The number, nature, and severity of adverse events will be carefully recorded. DISCUSSION: The study results will help clarify the safety and efficacy of TDKL as treatment for psoriasis with respect to both disease regression and recurrence rate. We expect that this study will provide high-quality evidence with important public health implications that may alter the approach to psoriasis management in China. TRIAL REGISTRATION: The trial has been registered at ClinicalTrials.gov (ID: NCT03942198).

GRP137 promotes cell proliferation and metastasis through regulation of the PI3K/AKT pathway in human ovarian cancer.

PURPOSE: Ovarian cancer is one of the leading causes of death for women worldwide. The present study aims to investigate the role of G protein-coupled receptor 137 (GPR137) in the biological activities of ovarian cancer cells. METHODS: (QUERY: Please supply Methods for Abstract) RESULTS: G protein-coupled receptor 137 was highly expressed in clinical ovarian cancer tissues and exhibited the highest protein levels in SKOV3 cells and OVCAR3 cells. Knockdown of GPR137 caused significant decreases in cell proliferative rates and colony formation abilities in SKOV3 cells and OVCAR3 cells and also inhibited the in vivo tumorigenesis in a xenograft model. It was observed that knockdown of GPR137 inhibited cell motility by up to 40% in SKOV3 cells and approximately 65% in OVCAR3 cells in wound-healing assay. Cell migration abilities were consistently inhibited by 68.2% in SKOV3 cells and 59.3% in OVCAR3 cells, whereas cell invasion abilities were inhibited by 64.0% and 74.2% in SKOV3 and OVCAR3 cells, respectively, after knockdown of GPR137. When GPR137 was depleted, epithelial markers were increased, while mesenchymal markers decreased. CONCLUSIONS: Our data suggest that GPR137 plays pro-oncogenic roles in ovarian cancer via regulation of the PI3K/AKT pathway. These observations might pave new insights into therapeutic strategies against human ovarian cancer.

Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus.

Stress-related alterations in brain-derived neurotrophic factor (BDNF) expression, a neurotrophin that plays a key role in synaptic plasticity, are believed to contribute to the pathophysiology of depression. Here, we show that in a chronic mild stress (CMS) model of depression the Gαi1 and Gαi3 subunits of heterotrimeric G proteins are down-regulated in the hippocampus, a key limbic structure associated with major depressive disorder. We provide evidence that Gαi1 and Gαi3 (Gαi1/3) are required for the activation of TrkB downstream signaling pathways. In mouse embryonic fibroblasts (MEFs) and CNS neurons, Gαi1/3 knockdown inhibited BDNF-induced tropomyosin-related kinase B (TrkB) endocytosis, adaptor protein activation, and Akt-mTORC1 and Erk-MAPK signaling. Functional studies show that Gαi1 and Gαi3 knockdown decreases the number of dendrites and dendritic spines in hippocampal neurons. In vivo, hippocampal Gαi1/3 knockdown after bilateral microinjection of lentiviral constructs containing Gαi1 and Gαi3 shRNA elicited depressive behaviors. Critically, exogenous expression of Gαi3 in the hippocampus reversed depressive behaviors in CMS mice. Similar results were observed in Gαi1/Gαi3 double-knockout mice, which exhibited severe depressive behaviors. These results demonstrate that heterotrimeric Gαi1 and Gαi3 proteins are essential for TrkB signaling and that disruption of Gαi1 or Gαi3 function could contribute to depressive behaviors.

[Detection of UGT1A1*28 Polymorphism Using Fragment Analysis].

BACKGROUND: Uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1), UGT1A1*28 polymorphism can reduce UGT1A1 enzymatic activity, which may lead to severe toxicities in patients who receive irinotecan. This study tries to build a fragment analysis method to detect UGT1A1*28 polymorphism. METHODS: A total of 286 blood specimens from the lung cancer patients who were hospitalized in Guangdong General Hospital between April 2014 to May 2015 were detected UGT1A1*28 polymorphism by fragment analysis method. RESULTS: Comparing with Sanger sequencing, precision and accuracy of the fragment analysis method were 100%. Of the 286 patients, 236 (82.5% harbored TA6/6 genotype, 48 (16.8%) TA 6/7 genotype and 2 (0.7%) TA7/7 genotype. CONCLUSIONS: Our data suggest hat the fragment analysis method is robust for detecting UGT1A1*28 polymorphism in clinical practice. It's simple, time-saving, and easy-to-carry.

Long Noncoding RNA MIR4697HG Promotes Cell Growth and Metastasis in Human Ovarian Cancer.

Ovarian cancer is one of the three most common gynecological malignant tumors worldwide. The prognosis of patients suffering from this malignancy remains poor because of limited therapeutic strategies. Herein, we investigated the role of a long noncoding RNA named MIR4697 host gene (MIR4697HG) in the cell growth and metastasis of ovarian cancer. Results showed that the transcriptional level of MIR4697HG in cancerous tissues increased twofold compared with that in adjacent noncancerous tissues. MIR4697HG was differentially expressed in ovarian cancer cell lines, with the highest levels in OVCAR3 and SKOV3 cells. MIR4697HG knockdown by specific shRNA significantly inhibited cell proliferation and colony formation in both OVCAR3 and SKOC3 cells. Consistently, in a xenograft model of ovarian cancer, MIR4697HG depletion also significantly restricted tumor volumes and weights. Furthermore, MIR4697HG knockdown inhibited cell migration and invasion capacities. Invasion ability was inhibited by 58% in SKOV3 cells and 40% in OVCAR3 cells, and migration ability was inhibited by 73% in SKOV3 cells and 62% in OVCAR3 cells after MIR4697HG knockdown. MIR4697HG knockdown also caused a decrease in matrix metalloprotease-9, phosphorylated ERK, and phosphorylated AKT. These data suggested that MIR4697HG promoted ovarian cancer growth and metastasis. The aggressive role of MIR4697HG in ovarian cancer may be related to the ERK and AKT signaling pathways.