The Predictive Value of Geriatric Nutritional Risk Index Combined with the GRACE Score in Predicting the Risk of One Year Poor Prognosis in Elderly Patients with Non-ST Segment Elevation Myocardial Infarction After PCI.

Background: As a nutritional indicator, a lower level of geriatric nutritional risk index (GNRI) has been suggested as a predictor for poor prognosis in acute coronary syndrome (ACS). However, whether GNRI could improve the predictive value of the Global Registry of Acute Coronary Events (GRACE) score for the prognosis in elderly patients with non-ST segment elevation myocardial infarction (NSTEMI) after PCI remains unclear. Methods: A total of 446 elderly patients with NSTEMI after percutaneous coronary intervention (PCI) were consecutively enrolled. Patients were divided into major adverse cardiovascular and cerebrovascular events (MACCE) group and control group according to the occurrence of MACCE during one year follow up. The clinical parameters including GNRI were compared to investigate the predictors for MACCE. The performance after the addition of GNRI to the GRACE score for predicting MACCE was determined. Results: A total of 68 patients developed MACCE. In unadjusted analyses, the rate of MACCE was significantly higher in the 93.8

Triglyceride glucose-body mass index as a novel predictor of slow coronary flow phenomenon in patients with ischemia and nonobstructive coronary arteries (INOCA).

BACKGROUND: The triglyceride glucose-body mass index (TyG-BMI index) has been suggested as a novel predictor of insulin resistance. However, its predictive value for slow coronary flow phenomenon (SCFP) in patients with ischemia and nonobstructive coronary arteries (INOCA) remains unclear. METHODS: We consecutively recruited 1625 patients with INOCA from February 2019 to February 2023 and divided them into two groups based on thrombolysis in myocardial infarction (TIMI) frame counts (TFCs): the SCFP group (n = 79) and the control group. A 1:2 age-matched case-control study was then performed. The TyG-BMI index was calculated as ln [plasma triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI. RESULTS: TyG-BMI index in the SCFP group (218.3 ± 25.2 vs 201.0 ± 26.5, P < .001) was significantly higher than in the normal controls. TyG-BMI index also increased with the number of coronary arteries involved in the SCFP. Multivariate logistic regression analysis showed that TyG-BMI, BMI, and TG were independent predictors for SCFP. Receiver operating characteristic (ROC) curve analysis showed that when the TyG-BMI index was above 206.7, the sensitivity and specificity were 88.6% and 68.5%, respectively, with an AUC of 0.809 (95% CI: 0.756-0.863, P = .027). Combined BMI with TG, the TyG-BMI index had a better predictive value for SCFP than BMI and TG (P < .001). CONCLUSION: The TyG-BMI index was an independent predictor for SCFP in INOCA patients, and it had a better predictive value than BMI and TG.

Development and validation of a predictive model for fetal cerebral maturation using ultrasound for fetuses with normal growth and fetal growth restriction.

Background: Investigation of fetal cerebral maturation (FCM) is necessary and important to provide crucial prognostic information for normal and high-risk fetuses. The study aimed to develop a valid and quantitative predictive model for assessing FCM using ultrasound and validate the model for fetuses with normal and restricted growth. Methods: This was a multicenter prospective observational study. Fetuses with normal growth recruited from a university teaching hospital (Center 1) and a municipal maternal unit (Center 2) were included in the training set and external validation set 1, respectively. The 124 growth-restricted fetuses enrolled in Center 1 were included in validation set 2. FCM was used to describe the gestational age (GA) in this study. The model was developed based on the sum of fetal cranial parameters (total fetal cranial parameters), including head circumference (HC) and depths of the insula (INS) and sylvian fissure (SF), parieto-occipital fissure (POF), and calcarine fissure (CF). A regression model, constructed based on total fetal cranial parameters and predicted GA, was established using the training set and validated using external validation set 1 and validation set 2. Results: The intra- and interobserver intraclass correlation coefficients for HC, and depths of the INS and SF, POF, and CF were >0.90. An exponential regression equation was used to predict FCM: predicted GA of FCM (weeks) =11.16 × exp (0.003 × total fetal cranial parameters) (P<0.001; adjusted R2=0.973), standard error of estimate, 0.67 weeks. The standard error of the predicted GA of FCM from the model was ±4.7 days. In the validation set 1, the mean standard error of the developed prediction model for FCM was 0.97 weeks. The predictive model showed that FCM was significantly delayed in validation set 2 (2.10±1.31 weeks, P<0.001), considering the GA per the last menstrual period. Conclusions: The predictive performance of the FCM model developed in this study was excellent, and the novel model may be a valuable investigative tool during clinical implementation.

Accuracy of Fasting Blood Glucose and Body Mass Index in Predicting Gestational Diabetes Mellitus in China.

BACKGROUND: Research suggests that lowering maternal morbidities associated with gestational diabetes mellitus (GDM) can be achieved with earlier risk group identification. AIMS: Therefore, the purpose of this study was to examine potential markers for identifying first-trimester pregnant women who are at high risk for developing GDM. METHODS: This was a retrospective cohort study. The pertinent maternal clinical data were retrieved prior to 13+6 weeks of gestation, and a binary logistic regression analysis was used to identify potential GDM predictors. The predictive accuracy was evaluated using the area below the receiver operating characteristics curves. RESULTS: In comparison to the control group, the GDM group had significantly higher mean values for age, body mass index (BMI), mean fasting blood glucose (FBG), and hemoglobin (p < 0.05). The Pearson's correlation coefficients indicated that the first-trimester FBG was significantly positively correlated with the second-trimester FBG. Higher FBG and BMI values were associated with an increased risk of developing GDM (odds ratio [OR] = 3.04, 95% confidence interval [CI] = 2.03-4.55 and OR = 1.18, 95% CI = 1.12-1.25). In terms of predicting GDM, the FBG parameter demonstrated the greatest area under the curve values (0.66), followed by the BMI parameter (0.69). For GDM prediction, the cut-off value for FBG was 4.32 mM, whereas that for BMI was 23.7 kg/m2. CONCLUSIONS: The first-trimester FBG and BMI could be utilized to predict gestational diabetes.

[Evidence mapping analysis of clinical research on traditional Chinese medicine in treatment of vertigo].

In this study, the evidence map system was used to sort out the clinical research evidence on traditional Chinese medicine(TCM) treatment of vertigo and understand the evidence distribution in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for the clinical randomized controlled trial(RCT) and systematic reviews/Meta-analysis on TCM treatment of vertigo in recent five years, and the evidence was analyzed and presented in the form of text and charts. The Cochrane handbook for systematic reviews of interventions was used to evaluate the quality of the clinical RCT, and the AMSTAR mea-surement tool was used to evaluate the quality of the systematic reviews/Meta-analysis. A total of 382 RCTs and eight systematic reviews/Meta-analysis were included. In recent five years, the number of published articles has been on the rise. There were many intervention measures and TCM therapies for vertigo. Outcome indicators mainly included clinical efficacy, TCM syndrome score, vertigo score, occurrence of adverse reactions, and effective rate. The overall quality of clinical RCT and systematic reviews/Meta-analysis was low. Most studies have proven the potential efficacy of TCM in treating vertigo, but there was still no clear clinical evidence of efficacy. The results show that TCM has advantages in the treatment of vertigo, but there are also problems. More high-quality studies are still lacking, suggesting that more large-sample and multi-center RCT should be conducted in the future, and the quality of relevant syste-matic reviews/Meta-analysis should be improved to fully explore the advantages of TCM in the treatment of vertigo, and provide strong support for the effectiveness and safety of TCM in the treatment of vertigo.

Photoinduced Copper-Catalyzed Aminoalkylation of Amino-Pendant Olefins.

The combination of photo and copper catalysts has emerged as a novel paradigm in organic catalysis, which provides access to the acceleration of chemical synthesis. Herein, we describe an aminoalkylation of amino-dependent olefins with maleimides through a cooperative photo/copper catalytic system. In this report, the strategy allows the generation of a broad complex of functionalized nitrogenous molecules including oxazolidinones, 2-pyrrolidones, imidazolidinones, thiazolidinones, pyridines, and piperidines in the absence of an external photosensitizer and base. The approach is achieved through a photoinduced Cu(I)/Cu(II)/Cu(III) complex species of nitrogen nucleophiles, intermolecular radical addition, and hydrogen atom transfer (HAT) processes. The plausible mechanism is investigated by a series of control experiments and theoretical tests, including radical scavenging experiments, deuterium labeling experiments, ultraviolet-visible absorption, and cyclic voltammetry (CV) tests.

Correlation between abnormal energy metabolism of ovarian granulosa cells and in vitro fertilization-embryo transfer outcomes in patients with polycystic ovary syndrome and obesity.

CONTEXT: Granulosa cells (GCs) that surround oocytes in mammalian reproduction play an active role in oocyte differentiation through proliferation and energy production. AIMS: This study aimed to investigate the characteristics of the energy metabolism of ovarian GCs and the influence of GCs on the early embryonic development in polycystic ovary syndrome (PCOS). METHODS: The clinical characteristics and in vitro fertilization-embryo transfer treatment outcomes of 39 patients with PCOS and 68 patients with simple tubal factor infertility who underwent controlled ovarian hyperstimulation were analyzed and summarized. The mitochondrial function and glucose metabolism level of the GCs were determined, as well as the content of oxidative stress markers in the follicular fluid (FF) of patients with and without PCOS. KEY RESULTS: When compared to the non-PCOS group, patients with PCOS had a significantly increased number of retrieved oocytes but a significantly decreased number of high-quality embryos, available embryos, and high-quality blastocyst formation (P < 0.05). Furthermore, the mitochondrial membrane potential, adenosine triphosphate level, and mitochondrial DNA (mtDNA) copy number decreased in the GCs, whereas the levels of reactive oxygen species increased (P < 0.01). The levels of malondialdehyde and 8-oxo-deoxyguanosine (8-OHdG) in the follicular fluid (FF) of the patients with PCOS were higher than those of the control group (P < 0.05), and superoxide dismutase was increased by compensation (P < 0.05). In the PCOS group, the expressions of GLUT1, LDHA, and PFKP were lower than those in the non-PCOS group, and glucose levels were higher. CONCLUSIONS: The low oocyte competence of PCOS may be associated with mitochondrial dysfunction and abnormal glycolysis. IMPLICATIONS: This research offers explanations for the possible connections influencing human ovarian folliculogenesis.

Chemodivergent Tandem Radical Cyclization of Alkene-Substituted Quinazolinones: Rapid Access to Mono- and Di-Alkylated Ring-Fused Quinazolinones.

Chemodivergent tandem radical cyclization offers exciting possibilities for the synthesis of structurally diverse cyclic compounds. Herein, we revealed a chemodivergent tandem cyclization of alkene-substituted quinazolinones under metal- and base-free conditions, this transformation is initiated by alkyl radicals produced from oxidant-induced α-C(sp3 )-H functionalization of alkyl nitriles or esters. The reaction resulted in the selective synthesis of a series of mono- and di-alkylated ring-fused quinazolinones by modulating the loading of oxidant, reaction temperature, and reaction time. Mechanistic investigations show that the mono-alkylated ring-fused quinazolinones is constructed by the key process of 1,2-hydrogen shift, whereas the di-alkylated ring-fused quinazolinones is mainly achieved through crucial steps of resonance and proton transfer. This protocol is the first example of remote second alkylation on the aromatic ring via α-C(sp3 )-H functionalization and difunctionalization achieved by association of two unsaturated bonds in radical cyclization.

Metal- and Base-Free Radical Cascade Cyclization/Hydrolysis of CN-Containing 1,6-Enynes with Ethers to Access Polyheterocycles.

A convenient and straightforward approach for the radical cascade cyclization/hydrolysis of CN-containing 1,6-enynes with simple ethers under metal- and base-free conditions is described. This strategy provides a variety of valuable ethers-substituted polyheterocycles via the construction of three C-C bonds, one C=O bond, and two new six-membered rings within a single procedure. The resulting products can smoothly undergo follow-up conversions to various useful scaffolds. The methodology shows excellent functional group tolerance, high step- and atom- economy, and mild reaction conditions, which can be further scaled up to gram quantity in a satisfactory yield.

Bacteria Associated with Granulomatous Lobular Mastitis and the Potential for Personalized Therapy.

Granulomatous lobular mastitis (GLM), also known as idiopathic granulomatous mastitis (IGM), is a chronic inflammatory lesion of the breast. The incidence of GLM has been increasing in recent years, especially among young women. The etiologies of GLM have not been fully elucidated but are associated with autoimmunity and bacterial infection. Bacteria, especially Corynebacterium species, play important roles in GLM. In this article, we review research progress regarding the bacteriology of GLM attained with the application of several new high-throughput detection techniques. Accurate detection might be important for deepening our understanding of the pathogenesis of GLM and hold promise for personalized GLM therapy.

New Insights of Corynebacterium kroppenstedtii in Granulomatous Lobular Mastitis based on Nanopore Sequencing.

BACKGROUND: The etiology of granulomatous lobular mastitis (GLM) remains unknown. This study aimed to detect bacteria in GLM using Nanopore sequencing and identify the relationship between GLM and Corynebacterium kroppenstedtii. METHODS AND MATERIALS: The bacterial detection on fresh samples (including breast pus and tissue) of 50 GLM patients using nanopore sequencing and culture methods. The bacterial detection rate of participants with different stages were compared and analyzed. Formalin-fixed and paraffin-embedded (FFPE) tissues from 39 patients were performed on Gram staining to identify Gram-positive bacilli (GPB) within lipid vacuoles. Moreover, the clinicopathological characteristics of GLM patients in different bacterial subgroups were also conducted. RESULTS: In 50 GLM patients, the detection rate of bacteria was 78% using nanopore sequencing method, especially in the early stage of GLM (over 80%), which was significantly higher than that using culture methods (24%, p < 0.001). The dominant bacteria were Corynebacterium species (64%), especially for the Corynebacterium kroppenstedtii. The detection rate of C. kroppenstedtii in nanopore sequencing method (56%) was higher than that in culture methods (16%, p < 0.001). Gram staining positive of bacteria in 7 patients, and 5 of them were C. kroppenstedtii. Thirty-one patients (31/39, 79.5%) exhibited typical histological structure of cystic neutrophilic granulomatous mastitis (CNGM), and eighteen patients detected with C. kroppenstedtii. CONCLUSION: Nanopore sequencing showed rapid and accurate bacteria detection over culture method in GLM patients. GLM is not sterile inflammation and closely related to C. kroppenstedtii. CNGM was associated with Corynebacterium infection, especially for C. kroppenstedtii.

Met-Controlled Allosteric Module of Neural Generation as A New Therapeutic Target in Rodent Brain Ischemia.

OBJECTIVE: To investigate a Met-controlled allosteric module (AM) of neural generation as a potential therapeutic target for brain ischemia. METHODS: We selected Markov clustering algorithm (MCL) to mine functional modules in the related target networks. According to the topological similarity, one functional module was predicted in the modules of baicalin (BA), jasminoidin (JA), cholic acid (CA), compared with I/R model modules. This functional module included three genes: Inppl1, Met and Dapk3 (IMD). By gene ontology enrichment analysis, biological process related to this functional module was obtained. This functional module participated in generation of neurons. Western blotting was applied to present the compound-dependent regulation of IMD. Co-immunoprecipitation was used to reveal the relationship among the three members. We used IF to determine the number of newborn neurons between compound treatment group and ischemia/reperfusion group. The expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were supposed to show the changing circumstances for neural generation under cerebral ischemia. RESULTS: Significant reduction in infarction volume and pathological changes were shown in the compound treatment groups compared with the I/R model group (P<0.05). Three nodes in one novel module of IMD were found to exert diverse compound-dependent ischemic-specific excitatory regulatory activities. An anti-ischemic excitatory allosteric module (AME) of generation of neurons (AME-GN) was validated successfully in vivo. Newborn neurons increased in BJC treatment group (P<0.05). The expression of VEGF and MMP-9 decreased in the compound treatment groups compared with the I/R model group (P<0.05). CONCLUSIONS: AME demonstrates effectiveness of our pioneering approach to the discovery of therapeutic target. The novel approach for AM discovery in an effort to identify therapeutic targets holds the promise of accelerating elucidation of underlying pharmacological mechanisms in cerebral ischemia.

Efficacy and Safety of Wenxin Granules and Propafenone in Treatment of Atrial Premature Beats: A Systematic Review and Meta-Analysis.

OBJECTIVE: A meta-analysis was conducted on the clinical efficacy and safety of Wenxin granules and propafenone for the therapy of atrial premature beats (APBs). METHODS: A randomized controlled trial (RCT) of Wenxin granules and propafenone in the therapy of APB was systematically searched until June 1, 2019. Meta-analysis was conducted with review manager (RevMan) 5.3. For the evaluation of methodological quality for randomized controlled trials, the Cochrane tool was used to assess the risk of bias. For the evaluation of the evidence quality, the online GRADEpro GDT was used. RESULTS: Eleven RCTs with 1149 participants were included in this study. It has been identified that Wenxin granules combined with propafenone have better clinical efficacy than the use of propafenone alone in the treatment of APB (OR = 3.89, 95% CI (2.03, 7.44), P < 0.0001, low-dose propafenone; OR = 4.24, 95% CI (1.32, 13.60), P = 0.02, high-dose propafenone). There is no difference in clinical efficacy between the Wenxin granules alone and high-dose propafenone in the treatment of APB (OR = 1.17, 95% CI (0.65, 2.11), P = 0.60), and Wenxin granules alone are superior to the low-dose propafenone in the treatment of APB (OR = 2.56, 95% CI (1.34, 4.89), P = 0.004). Wenxin granules combined with propafenone can reduce the incidence of sinus bradycardia caused by propafenone (OR = 0.15, 95% CI (0.03, 0.70), P = 0.02). There was no significant difference between Wenxin granules combined with propafenone and propafenone alone in causing the atrioventricular block, dizziness, xerostomia, gastrointestinal symptoms, and tongue paresthesia. There was no significant difference between Wenxin granules alone and propafenone alone in causing dizziness, xerostomia, gastrointestinal symptoms, tongue paresthesia, frequent premature ventricular contractions, and prolongation of R-R interval. CONCLUSION: Very low-quality evidence showed that Wenxin granules may be superior to low-dose propafenone in the treatment of APB. Wenxin granules may reduce the incidence of sinus bradycardia caused by propafenone. Limited by the quality of included RCTs, the conclusions of this study still need further verification.

KIF15 Promotes Proliferation and Growth of Hepatocellular Carcinoma.

Liver cancer is thought as the most common human malignancy worldwide, and hepatocellular carcinoma (HCC) accounts for nearly 90% liver cancer. Due to its poor early diagnosis and limited treatment, HCC has therefore become the most lethal malignant cancers in the world. Recently, molecular targeted therapies showed great promise in the treatment of HCC, and novel molecular therapeutic targets is urgently needed. KIF15 is a microtubule-dependent motor protein involved in multiple cell processes, such as cell division. Additionally, KIF15 has been reported to participate in the growth of various types of tumors; however, the relation between KIF15 and HCC is unclear. Herein, our study investigated the possible role of KIF15 on the progression of HCC and found that KIF15 has high expression in tumor samples from HCC patients. KIF15 could play a critical role in the regulation of cell proliferation of HCC, which was proved by in vitro and in vivo assays. In conclusion, this study confirmed that KIF15 could be a novel therapeutic target for the treatment of HCC.

Efficacy in pigs of a new inactivated vaccine combining porcine circovirus type 2 and Mycoplasma hyorhinis.

Coinfection with porcine circovirus type 2 (PCV2) and Mycoplasma hyorhinis (Mhr) can induce more-severe disease than a single infection with either. We evaluated the efficacy of a new vaccine combining inactivated PCV2 and Mhr, in a model of PCV2 and Mhr infection. Twenty-five 35-day-old PCV2- and Mhr-free pigs were randomly divided into five groups, with five pigs in each group. The pigs in groups 1 and 2 were vaccinated with the combined vaccine and then challenged with Mhr or PCV2, respectively. The pigs in groups 3 and 4 were not vaccinated and then challenged with PCV2 or Mhr, respectively, and group 5 was used as the unvaccinated unchallenged control. Two weeks after booster immunization via the intramuscular route, all the pigs except those in control group 5 were challenged with PCV2 or Mhr. All the pigs were euthanized 28 days after challenge. The pigs in vaccinated groups 1 and 2 showed a significant increase in weight after challenge with PCV2 or Mhr (P < 0.001), with an average daily gain (ADG) of 0.315 kg compared with unvaccinated groups 3 and 4 (0.279 kg). Mhr was isolated from the unvaccinated pig lungs after Mhr challenge, whereas it was not isolated from the vaccinated pigs. No PCV2 or Mhr was detected with PCR or histochemical staining in vaccinated groups 1 and 2. A statistical analysis showed that the PCV2 and Mhr combined vaccine providing protected against PCV2 infection causing viremia and inguinal lymphadenopathy (5 pigs protected out 5) or against Mhr infection causing fiber inflammation (4 pigs out 5). Thus, we have developed an effective combined vaccine for the prevention and control of PCV2 or Mhr infections in swine herds, this will help reduce prevalence of PCV2 and Mhr coinfections.

The efficacy and safety of olaparib in the treatment of cancers: a meta-analysis of randomized controlled trials.

PURPOSE: PARP inhibition is an exciting new anticancer strategy. As the first PARP inhibitor approved for the treatment of advanced BRCA-mutated ovarian cancer, olaparib has proven to be effective in the treatment of several solid tumors. We performed a meta-analysis of published randomized controlled trials to evaluate the efficacy and safety of olaparib in cancer patients. METHODS: PubMed, Embase, and oncology-conference proceedings were searched for relevant studies. End points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3/4 adverse events. Pooled hazard ratio (HR)/risk ratio (RR) and 95% CI were calculated using random or fixed-effect models. RESULTS: Eight trials involving 1,957 patients were ultimately identified. The pooled analysis demonstrated that olaparib treatment significantly improved PFS (HR 0.62, 95% CI 0.47-0.82; P=0.001), OS (HR 0.82, 95% CI 0.73-0.93; P=0.001), and ORR (RR 1.38, 95% CI 1.16-1.65; P<0.001) when compared with therapy not containing olaparib. This association was further confirmed by sensitivity analysis. Additionally, olaparib treatment offered a significant survival benefit for patients with BRCA mutation. Moreover, treatment with olaparib was associated with a significant increase in risk of severe anemia. CONCLUSION: Olaparib treatment has better treatment response compared with therapy not containing olaparib, whereas olaparib can increase the risk of severe anemia.

Amyloid ß-42 induces neuronal apoptosis by targeting mitochondria.

Alzheimer's disease (AD), with a typical pathological hallmark of amyloid­beta (Aß)­containing plaques and neurofibrillary tangles, is one of the most common types of chronic neurodegenerative diseases. Aß oligomers serve a crucial role in the pathogenesis of AD, and lead to neuronal loss. However, the precise mechanism of Aß oligomers in AD remains to be elucidated. The present study demonstrated that 10 µM Aß­42 activated the caspase signaling pathway, and induced significant apoptosis in primary cultured mouse cerebral cortical neurons. The results of reverse transcription­quantitative polymerase chain reaction and western blotting demonstrated that Aß­42 (10 µM) also significantly upregulated the transcription and expression of the mitochondrial fission protein dynamin­related protein 1 (Drp1), and downregulated the transcription and expression of mitochondrial fusion proteins, including mitofusin 1/2 (Mfn1/2) and mitochondrial dynamin like GTPase (OPA­1). Neurons were transfected with pDsRed2­Mito for mitochondrial imaging, which revealed that 10 µM Aß­42 induced mitochondrial fission in cortical neurons. In addition, 2',7'­dichlorodihydrofluorescein diacetate and tetramethylrhodamine ethyl ester staining indicated that Aß­42 increased the reactive oxygen species (ROS) level and reduced mitochondrial membrane potential in neurons. Inhibition of Drp1 activity by Mdivi­1 efficiently prevented Aß­42­induced ROS production and disruption of mitochondrial membrane potential. Loss of mitochondrial membrane potential may activate PTEN­induced putative kinase 1 (Pink1), the prominent sensor for mitochondrial damage, and trigger the process of mitophagy to remove the damaged mitochondria. In the present study, western blotting revealed that the levels of autophagy marker microtubule­associated proteins 1A/1B light chain 3B (LC3B) and Pink1 were upregulated after Aß­42 stimulation. In conclusion, these data indicated that Aß­42 induces neuronal apoptosis by targeting mitochondria, including promotion of mitochondrial fission, disruption of mitochondrial membrane potential, increasing intracellular ROS level and activation of the process of mitophagy. Therefore, mitochondria may represent a potential therapeutic target for AD in the future.

Involvement of mitochondrial dynamics in the antineoplastic activity of cisplatin in murine leukemia L1210 cells.

Leukemia is a type of hematopoietic stem cell malignant cloned disease with high mortality. Cisplatin-based chemotherapy is one of the most common treatments for leukemia. Similar to other chemotherapeutic agents, cisplatin resistance has become a serious issue in cancer therapy. In the present study, we investigated the role of mitochondrial dynamics in the antineoplastic activity of cisplatin in murine leukemia L1210 cells. Firstly, the L1210 cell line resistant to cisplatin (L1210/DDP) was established. Compared to its parental cell line, the IC50 value of cisplatin in the L1210/DDP cells was increased 10-fold. Mitofusins (Mfn1 and Mfn2), mitochondrial outer membrane fusion proteins, were markedly upregulated in the L1210/DDP cells, whereas the expression of fission protein Drp1 and inner membrane fusion protein OPA1 were not significantly altered. In addition, mitofusins were also upregulated in the parental L1210 cells subjected to cisplatin stress. To investigate the role of mitochondrial dynamics in the antineoplastic activity of cisplatin, the effect of mitochondrial division inhibitor (Mdivi)-1 on cisplatin­induced cell death, caspase-3 cleavage and ROS production was examined in L1210 cells. We found that 5 µM of Mdivi-1 efficiently attenuated cisplatin-induced cell death, caspase activation and intracellular ROS increase in L1210 cells. Our data indicated that mitochondrial dynamics play an important role in the antineoplastic activity of cisplatin, and mitofusin-mediated mitochondrial fusion may be involved in the process of cisplatin resistance in leukemia cells. Therefore, the present study revealed that mitochondrial dynamics may be a potential target used to improve the antineoplastic activity of cisplatin in leukemia in the future.

Study on droplet microfluidic chips for drug screening against Candida albicans / 药学学报

A droplet microfluidic chip system was developed for drug screening against Candida albicans. The microfluidic chip was designed and prepared for the formation of droplets. Alamar blue was selected as an indicator for its characteristic of fluorescence mission in live cells. Four antifungal drugs (amphotericin B, caspofungin, 5-fluorocytosine, terbinafine) and a new drug (iodiconazole) were selected as model drugs to test the microfluidic chip approach. At the same time, 96-well microplate method was performed to verify the applicability of the chip method. The results showed that the developed droplet microfluidic chip platform was able to complete the antifungal susceptibility test within 2 h. In comparison with the 96-well microplate method, the microfluidic chip method showed a consistence of 100% with regard to the minimum inhibition concentrations and less reagent consumption. The new droplet microfluidic chip method is simple, rapid and suitable for rapid screening of antifungal drugs.

Targeting the pseudorabies virus DNA polymerase processivity factor UL42 by RNA interference efficiently inhibits viral replication.

RNA interference (RNAi) is a conserved gene-silencing mechanism in which small interfering RNAs (siRNAs) induce the sequence-specific degradation of homologous RNAs. It has been shown to be a novel and effective antiviral therapy against a wide range of viruses. The pseudorabies virus (PRV) processivity factor UL42 can enhance the catalytic activity of the DNA polymerase and is essential for viral replication, thus it may represent a potential drug target of antiviral therapy against PRV infection. Here, we synthesized three siRNAs (siR-386, siR-517, and siR-849) directed against UL42 and determined their antiviral activities in cell culture. We first examined the kinetics of UL42 expression and found it was expressed with early kinetics during PRV replication. We verified that siR-386, siR-517, and siR-849 efficiently inhibited UL42 expression in an in vitro transfection system, thereby validating their inhibitory effects. Furthermore, we confirmed that these three siRNAs induced potent inhibitory effects on UL42 expression after PRV infection, comparable to the positive control siRNA, siR-1046, directed against the PRV DNA polymerase, the UL30 gene product, which is essential for virus replication. In addition, PRV replication was markedly reduced upon downregulation of UL42 expression. These results indicate that UL42-targeted RNAi efficiently inhibits target gene expression and impairs viral replication. This study provides a new clue for the design of an intervention strategy against herpesviruses by targeting their processivity factors.