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Objective: Treatment with TNF-α inhibitors improve psoriasis with minimize/minor neutrophils infiltration and CXCL-1/8 expression in psoriatic lesions. However, the fine mechanism of TNF-α initiating psoriatic inflammation by tuning keratinocytes is unclear. Our previous research identified the deficiency of intracellular galectin-3 was sufficient to promote psoriasis inflammation characterized by neutrophil accumulation. This study aims to investigate whether TNF-α participated in psoriasis development through dysregulating galectin-3 expression., Methods: mRNA levels were assessed through quantitative real-time PCR. Flow cytometry was used to detect cell cycle/apoptosis. Western blot was used to evaluate the activation of the NF-κB signaling pathway. HE staining and immunochemistry were used to detect epidermal thickness and MPO expression, respectively. Specific small interfering RNA (siRNA) was used to knock down hsa-miR-27a-3p while plasmids transfection was used to overexpress galectin-3. Further, the multiMiR R package was utilized to predict microRNA-target interaction., Results and Discussion: We found that TNF-α stimulation altered cell proliferation and differentiation and promoted the production of psoriasis-related inflammatory mediators along with the inhibition of galectin-3 expression in keratinocytes. Supplement of galectin-3 could counteract the rise of CXCL-1/8 but not the other phenotypes of keratinocytes induced by TNF-α. Mechanistically, inhibition of the NF-κB signaling pathway could counteract the decrease of galectin-3 and the increase of hsa-miR-27a-3p expression whereas silence of hsa-miR-27a-3p could counteract the decrease of galectin-3 expression induced by TNF-α treatment in keratinocytes. Intradermal injection of murine anti-CXCL-2 antibody greatly alleviated imiquimod-induced psoriasis-like dermatitis., Conclusion: TNF-α initiates psoriatic inflammation by increasing CXCL-1/8 in keratinocytes mediated by the axis of NF-κB-hsa-miR-27a-3p-galectin-3 pathway.

Objective: Schizophrenia (SZ) is associated with cognitive impairment, and it is known that the activity of cAMP response element binding protein (CREB) decreases in the brain of SZ patients. The previous study conducted by the investigators revealed that the upregulation of CREB improves the MK801-related SZ cognitive deficit. The present study further investigates the mechanism on how CREB deficiency is associated with SZ-related cognitive impairment., Methods: MK-801 was used to induce SZ in rats. Western blotting and immunofluorescence were performed to investigate CREB and the CREB-related pathway implicated in MK801 rats. The long-term potentiation and behavioral tests were performed to assess the synaptic plasticity and cognitive impairment, respectively., Results: The phosphorylation of CREB at Ser133 decreased in the hippocampus of SZ rats. Interestingly, among the upstream kinases of CREB, merely ERK1/2 was downregulated, while CaMKII and PKA remained unchanged in the brain of MK801-related SZ rats. The inhibition of ERK1/2 by PD98059 reduced the phosphorylation of CREB-Ser133, and induced synaptic dysfunction in primary hippocampal neurons. Conversely, the activation of CREB attenuated the ERK1/2 inhibitor-induced synaptic and cognitive impairment., Conclusion: These present findings partially suggest that the deficiency of the ERK1/2-CREB pathway is involved in MK801-related SZ cognitive impairment. The activation of the ERK1/2-CREB pathway may be therapeutically useful for treating SZ cognitive deficits., (© 2023. Huazhong University of Science and Technology.)

Background: Angiogenesis is an indispensable step in the growth and invasiveness of breast cancers involving a series of exquisite molecular steps. Pro-angiogenic factors, including vascular endothelial growth factor (VEGF), have been recognized as pivotal therapeutic targets in the treatment of breast cancer. More recently, a highly conserved transcription factor Twist has been reported to be involved in tumor angiogenesis and metastasis., Methods: The expression of VEGF-C and Twist was immunohistochemically determined in tissue samples of primary tumors from 408 patients undergoing curative surgical resection for breast cancer. The correlations of VEGF-C and Twist expressions with clinicopathologic parameters as well as survival outcomes were evaluated., Results: Of the 408 patients evaluated, approximately 70% had high expression of VEGF-C which was significantly associated with advanced tumor stages (P = 0.019). Similarly, VEGF-C expression was associated with the proliferation index Ki67, N3 lymph node metastasis, and D2-40-positive lymphatic vessel invasion (LVI) in a univariate analysis. Furthermore, patients with high expressions of VEGF-C and Twist (V + T+) had significantly increased lymph node metastasis, higher clinical stage, and worse disease-free survival, DFS (P = 0.001) and overall survival, OS (P = 0.011)., Conclusions: Our results suggested that co-expression of VEGF-C and Twist was associated with larger tumor size, higher numbers of lymph node involvement, D2-40-positive LVI, higher risk of distant metastasis, and worse DFS or OS in breast cancer patients.

Recent studies indicate that the long noncoding RNA ATB (lncATB) can induce the epithelial-mesenchymal transition (EMT) in cancer cells, but the specific cellular targets of lncATB require further investigation. In the present study, the upregulation of lncATB in breast cancer cells was validated in a TGF-β-induced EMT model. Gain- and loss-of-function studies demonstrated that lncATB enhanced cell migration, invasion and clonogenicity in vitro and in vivo. LncATB promoted the EMT by acting as a sponge for the miR-200 family and restoring Twist1 expression. Subsequently, the clinical significance of lncATB was investigated in a cohort of breast cancer patients (N = 131). Higher lncATB expression was correlated with increased nodal metastasis (P = 0.036) and advanced clinical stage (P = 0.011) as well as shorter disease-free survival (P = 0.043) and overall survival (P = 0.046). These findings define Twist1 as a major target of lncATB in the induction of the EMT and highlight lncATB as a biomarker in breast cancer patients.

A retrospective analysis was performed in two major HIV/AIDS referral hospitals in Beijing to evaluate the prevalence of Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterial (NTM) infections in HIV-infected patients. A total of 627 patients' data were reviewed, and 102 (16.3%) patients were diagnosed with culture-confirmed mycobacterial infection, including 84 with MTB, 16 with NTM, and 2 with both MTB and NTM. The most frequent clinical complication by mycobacterial infection was pulmonary infection (48/102, 47.1%). The overall rates of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) were 11.9% and 3.4%, respectively. This study underlines the urgent need to intensify screening for mycobacteria coinfection with HIV and to prevent the spread of drug-resistant TB among HIV-infected patients., (Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Although increasing evidences suggest a relationship between hypertension and brain function for years, it is still unclear whether hypertension constitutes a risk factor for cognitive decline and its underlying mechanism. In the present study, an experimental animal model of hypertension simply by feeding rats with high salt diet was employed. We found that long-term high salt intake caused a marked increase of systolic blood pressure linked to a declined regional cerebral blood flow. Fear conditioning and morris water maze behavioral test revealed that high salt diet induced hippocampal dependent spatial reference memory deficits, while a decreased synaptogenesis without neuronal loss in hippocampus was observed in high salt treated rats. Furthermore, we found that high salt induced a decrease of intracellular calcium, which inactivated CaMK II and resulted in dephosphorylation of CREB at Ser133. These findings suggest a novel etiopathogenic mechanism of cognitive deficit induced by hypertension, which is initiated by high salt diet., Competing Interests: CONFLICTS OF INTEREST The authors of this manuscript have no conflicts of interest to declare.

Breast reconstruction with transverse rectus abdominis myocutaneous (TRAM) flap is challenging in patients with low midline abdominal scar. In this study, we aimed to investigate the clinical feasibility of immediate breast reconstruction using single-pedicle TRAM (SP-TRAM) flaps in patients with low midline abdominal scar. There were 4 strict selection criteria: 1) presence at least 3 perforators on the pedicle side; 2) perforators with regional average flow velocity of >20 cm/s; 3) upper edge of the abdominal scar at least 4 cm from the umbilicus; and 4) scar age >1 year. Eight breast cancer patients with low midline abdominal scar (scar group) and 20 without (control group) underwent immediate breast reconstruction with SP-TRAM flaps consisting of zone I and III and zone II tissues. Flap complications, donor-site complications, and cosmetic results were compared between the two groups. All flaps survived and both groups presented similar flap and donor site complications, including fat necrosis, seroma, hematoma, infection, delayed wound healing, and abdominal hernia, and patients in both groups had similar aesthetic results (p > 0.05). Thus, the study demonstrated that breast reconstruction using SP-TRAM flap was a safe approach in carefully selected patients with low midline abdominal scar.

Objective: To study the effects of different hormone induced bulb of Fritillaria cirrhosa seedling leaves, in order to provide an effective way to expant Fritillaria cirrhosa source., Methods: Fritillaria cirrhosa seedling leaves were used as explants, orthogonal test was carried out to study the medium consisting of 6-BA, NAA, 2, 4-D and KT, and proliferation induced by direct bulb. Induction rate and average number of bulb producing was treated as the assessment indices, and the content of alkaloid of bulb was determined., Results: The best medium formula for Fritillaria cirrhosa tissue culture seedling was MS+6-BA 2.0 mg/L +NAA 1.0mg/L +KT 1.0mg/L, the bulb induction rate was 83.37% and the average number of bulb was 17.27. The alkaloid content of induced bulb was 0.389%, which was 1.64 times that of wild Fritillaria cirrhosa bulb., Conclusion: This study provides a simple and rapid mehod for the production of tissue culture of Fritillaria cirrhosa bulb. It is useful for reasonable development and utilization of Fritillaria cirrhosa resources, as well as improvement of the quality of medicinal materials.

A novel and concise scheme has been developed successfully for the syntheses of N-substituted fagomine derivatives. The transformation of lactone (2) to 1,5-diol (3) was carried on with high yield (93-95%). The cyclization of 4 to 5 is a high stereoselective reaction (de value > 98%). It is disclosed that bulky substituent at N atom of the piperidine decreases the inhibition activity except those substituents having the ability of solvation or forming disulfide bond with M444 at the active site of α-glycosidase, which enhance the interaction with enzyme. Compounds with S-configuration at C-3 show greater activity than those with R-configuration. The structure-activity relationship study is also supported by molecular docking analysis., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Bioluminescence reporter proteins have been widely used in the development of tools for monitoring biological events in living cells. Currently, some assays like flow cytometry analysis are available for studying DNA synthetic phase (S-phase) targeted anti-cancer drug activity in vitro; however, techniques for imaging of in vivo models remain limited. Cyclin A2 is known to promote S-phase entry in mammals. Its expression levels are low during G1-phase, but they increase at the onset of S-phase. Cyclin A2 is degraded during prometaphase by ubiquitin-dependent, proteasome-mediated proteolysis. In this study, we have developed a cyclin A2-luciferase (CYCA-Luc) fusion protein targeted for ubiquitin-proteasome dependent degradation, and have evaluated its utility in screening S-phase targeted anti-cancer drugs. Similar to endogenous cyclin A2, CYCA-Luc accumulates during S-phase and is degraded during G2/M-phase. Using Cdc20 siRNA we have demonstrated that Cdc20 can mediate CYCA-Luc degradation. Moreover, using noninvasive bioluminescent imaging, we demonstrated accumulation of CYCA-Luc in response to 10-hydroxycamptothecin (HCPT), an S-phase targeted anti-cancer drug, in human tumor cells in vivo and in vitro. Our results indicate that a CYCA-Luc fusion reporter system can be used to monitor S-phase of cell cycle, and evaluate pharmacological activity of anti-cancer drug HCPT in real time in vitro and in vivo, and is likely to provide an important tool for screening such drugs.

Background: There is limited data on the clinical outcome of patients with pandemic H1N1 (pH1N1) pneumonia who received oseltamivir treatment, especially when the treatment was administered more than 48 hours after symptom onset., Methods: During the pandemic in 2009, a cohort of pH1N1 influenza pneumonia was built in China, and their clinical information was collected systematically, and analyzed with Cox models., Results: 920 adults and 541 children with pneumonia who didn't receive corticosteroids were analyzed. In-hospital mortality was higher in adults who did not receive antiviral therapy (18.2%) than those with who received oseltamivir ≤ 2 days (2.9%), between 2-5 days (4.6%) and >5 days after illness onset (4.9%), p<0.01. A similar trend was observed in pediatric patients. Cox regression showed that at 60 days after symptoms onset, 11 patients (10.8%) who did not receive antivirals died versus 4 (1.8%), 18 (3.3%), and 23 (3.7%) patients whose oseltamivir treatment was started ≤ 2 days, between 2-5 days, and >5 days, respectively. For males patients, aged ≥ 14 years and baseline PaO(2)/FiO(2)<200, oseltamivir administration reduced the mortality risk by 92.1%, 88% and 83.5%, respectively. Higher doses of oseltamivir (>3.8 mg/kg/d) did not improve clinical outcome (mortality, higher dose 2.5% vs standard dose 2.8%, p>0.05)., Conclusions: Antiviral therapy might reduce mortality of patients with pH1N1 pneumonia, even when initiated more than 48 hours after onset of illness. Greater protective effects might be in males, patients aged 14-60 years, and patients with PaO(2)/FiO(2)<200.

Human papillomavirus type 16 (HPV16) E7 is a viral oncoprotein believed to play a major role in cervical cancer. In this study, an antagonist peptide against HPV16E7 protein was first identified from screening the c7c phage display peptide library. The binding specificity and affinity of the selected peptide to HPV16E7 were tested by competitive enzyme-linked immunosorbent assay (ELISA). The antagonist peptide showed obvious anti-tumor efficacy both in cell lines and animal tumor models. Significant cell proliferation inhibition with high specificity was noted when HPV16-positive cells were treated with the peptide. This anti-tumor efficacy was resulted from overriding the activities of HPV16E7 and reactivating the pRb/E2F pathway, as shown by a series of experiments. Flow cytometry analysis revealed that the selected peptide induced G1 arrest in a dose-dependent manner. Competitive ELISA, pull down, and Co-IP experiments indicated that the selected peptide disrupted the interaction between HPV16E7 and pRb proteins both in vitro and in vivo. Luciferase reporter assay verified that transcription activities of E2F were suppressed by the peptide through restoration of pRb. RT-PCR and Western blot revealed that it reduced cyclins A, D1, and E1 expression, and led to HPV16E7 protein degradation, but pRb protein stabilization. The current study suggests that this specific peptide may serve as a potential therapeutic agent for HPV16-positive cervical cancer.

Reaction of two tripodal ligands, 2,4,6-tris(4-((2-methyl-benzimidazol-1-yl)methyl)phenyl)-1,3,5-triazine (L1) and 1,3,5-tris(4-((2-methyl-benzimidazol-1-yl)methyl)phenyl)benzene (L2), with AgSbF6 led to formation of two types (6,3) networks in one single crystal, of which one is three-fold Borromean topologically entangled while the other is independent, showing the same chirality and sandwiched Borromean stacking.

To study the prevalence of drug resistance mutations among HAART (highly active anti-retroviral therapy) naive subjects with HIV-1 subtype B infection, evaluate the correlation between major mutations and viral loads. Additionally, to investigate the primary resistance spectrum in the central plains of China and provide some guidance for the choice of antiretroviral drugs (ARV). Drug resistance mutations and viral loads were measured in 78 treatment-naïve patients with HIV infection and the results were analyzed with descriptive statistical and multiple statistical analysis. The most common mutations were L63P, V77I and I93L, which belong to minor mutations of the proteinase gene, and none of which had any relation to viral loads. The major mutations, which were mainly K103N and Q151M, were less frequent in China than those in other countries. There was a certain correlation between viral loads and I93IL according to stepwise regression analysis. The incidence of primary mutations among HAART naïve patients was lower in China's central plains than that in other countries, and the most common mutations had no relation to viral loads. Though major mutations affecting choice of ARV are not common in China, they deserve further attention.

Objective: To evaluate the influence of big Y chromosome on the outcomes of in vitro fertilization and embryo transfer., Methods: Data of 127 cycles of IVF/ICSI-ET, performed in our Reproductive Medicine Center from March 2001 to June 2003 were analyzed. The patients were divided into two groups according to the length of chromosome: Group A, 56 cycles with big Y chromosome, Results: No significant difference was observed in the quality of embryos and in the and Group B, 71 cycles with normal karyotype. rates of fertilization, cleavage, clinical pregnancy, implantation, miscarriage, ectopic pregnancy, dead infant delivery, malformation,, Conclusion: Big Y chromosome has no significant influence on the baby boy delivery and baby girl delivery between the two groups. development of embryos and the outcome of pregnancy.

Objective: To observe effect of opening point method of ziwu liuzhu on myocardial ischemia in the patient of stroke., Methods: Thirty cases of stroke with myocardial ischemia were treated with opening acupoint according to time of the combination of reinforcing mother point and reducing son point of the heart channel in nazi method of ziwu liuzhu, and 30 cases in the control group were treated with acupuncture at Guangming (GB 37). Changes of electrocardiogram before and after treatment were recorded., Results: ST-T segment raised significantly 30 min after treatment with ziwu liuzhu needling method as compared with the control group (P < 0.05), the treatment group being better than the control group., Conclusion: Excessive and deficient changes of the qi and blood in the meridians and collaterals are correlated with time rhythm, and ziwu liuzhu needling method can increase clinical therapeutic effect.