Kurarinone alleviated Parkinson's disease via stabilization of epoxyeicosatrienoic acids in animal model.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by loss of dopaminergic neurons in the substantia nigra (SN), causing bradykinesia and rest tremors. Although the molecular mechanism of PD is still not fully understood, neuroinflammation has a key role in the damage of dopaminergic neurons. Herein, we found that kurarinone, a unique natural product from Sophora flavescens, alleviated the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral deficits and dopaminergic neurotoxicity, including the losses of neurotransmitters and tyrosine hydroxylase (TH)-positive cells (SN and striatum [STR]). Furthermore, kurarinone attenuated the MPTP-mediated neuroinflammation via suppressing the activation of microglia involved in the nuclear factor kappa B signaling pathway. The proteomics result of the solvent-induced protein precipitation and thermal proteome profiling suggest that the soluble epoxide hydrolase (sEH) enzyme, which is associated with the neuroinflammation of PD, is a promising target of kurarinone. This is supported by the increase of plasma epoxyeicosatrienoic acids (sEH substrates) and the decrease of dihydroxyeicosatrienoic acids (sEH products), and the results of in vitro inhibition kinetics, surface plasmon resonance, and cocrystallization of kurarinone with sEH revealed that this natural compound is an uncompetitive inhibitor. In addition, sEH knockout (KO) attenuated the progression of PD, and sEH KO plus kurarinone did not further reduce the protection of PD in MPTP-induced PD mice. These findings suggest that kurarinone could be a potential natural candidate for the treatment of PD, possibly through sEH inhibition.

Effective Descriptor for Screening Single-Molecule Conductance Switches.

The adsorption-type molecular switch exhibits bistable states with an equivalently long lifetime at the organic/inorganic interface, promising reliable switching behavior and superior assembly ability in the electronic circuits at the molecular scale. However, the number of reported adsorption-type molecular switches is currently less than 10, and exploring these molecular switches poses a formidable challenge due to the intricate interplay occurring at the interface. To address this challenge, we have developed a model enabling the identification of diverse molecular switches on metal surfaces based on easily accessible physical characteristics. These characteristics primarily include the metal valency electron concentration, the work function of metal surfaces, and the electronegativity difference of molecules. Using this model, we identified 56 new molecular switches. Employing the gradient descent algorithm and statistical linear discriminant analysis, we constructed an explicit descriptor that establishes a relationship between the interfacial structure and chemical environment and the stability of molecular switches. The model's accuracy was validated through density functional theory calculations, achieving a 90% accuracy for aromatic molecular switches. The conductive switching behaviors were further confirmed by nonequilibrium Green's function transport calculations.

Evidence for widespread existence of functional novel and non-canonical human transcripts.

BACKGROUND: Fraction of functional sequence in the human genome remains a key unresolved question in Biology and the subject of vigorous debate. While a plethora of studies have connected a significant fraction of human DNA to various biochemical processes, the classical definition of function requires evidence of effects on cellular or organismal fitness that such studies do not provide. Although multiple high-throughput reverse genetics screens have been developed to address this issue, they are limited to annotated genomic elements and suffer from non-specific effects, arguing for a strong need to develop additional functional genomics approaches. RESULTS: In this work, we established a high-throughput lentivirus-based insertional mutagenesis strategy as a forward genetics screen tool in aneuploid cells. Application of this approach to human cell lines in multiple phenotypic screens suggested the presence of many yet uncharacterized functional elements in the human genome, represented at least in part by novel exons of known and novel genes. The novel transcripts containing these exons can be massively, up to thousands-fold, induced by specific stresses, and at least some can represent bi-cistronic protein-coding mRNAs. CONCLUSIONS: Altogether, these results argue that many unannotated and non-canonical human transcripts, including those that appear as aberrant splice products, have biological relevance under specific biological conditions.

SIRT3 regulates mitophagy in liver fibrosis through deacetylation of PINK1/NIPSNAP1.

Damaged mitochondria, a key factor in liver fibrosis, can be removed by the mitophagy pathway to maintain homeostasis of the intracellular environment to alleviate the development of fibrosis. PINK1 (PTEN-induced kinase 1) and NIPSNAP1 (nonneuronal SNAP25-like protein 1), which cooperatively regulate mitophagy, have been predicted to include the sites of lysine acetylation related to SIRT3 (mitochondrial deacetylase sirtuin 3). Our study aimed to discuss whether SIRT3 deacetylates PINK1 and NIPSNAP1 to regulate mitophagy in liver fibrosis. Carbon tetrachloride (CCl4 )-induced liver fibrosis as an in vivo model and LX-2 cells as activated cells were used to simulate liver fibrosis. SIRT3 expression was significantly decreased in mice in response to CCl4 , and SIRT3 knockout in vivo significantly deepened the severity of liver fibrosis, as indicated by increased α-SMA and Col1a1 levels both in vivo and in vitro. SIRT3 overexpression decreased α-SMA and Col1a1 levels. Furthermore, SIRT3 significantly regulated mitophagy in liver fibrosis, as demonstrated by LC3-Ⅱ/Ⅰ and p62 expression and colocalization between TOM20 and LAMP1. Importantly, PINK1 and NIPSNAP1 expression was also decreased in liver fibrosis, and PINK1 and NIPSNAP1 overexpression significantly improved mitophagy and attenuated ECM production. Furthermore, after simultaneously interfering with PINK1 or NIPSNAP1 and overexpressing SIRT3, the effect of SIRT3 on improving mitophagy and alleviating liver fibrosis was disrupted. Mechanistically, we show that SIRT3, as a mitochondrial deacetylase, specifically regulates the acetylation of PINK1 and NIPSNAP1 to mediate the mitophagy pathway in liver fibrosis. SIRT3-mediated PINK1 and NIPSNAP1 deacetylation is a novel molecular mechanism in liver fibrosis.

Outcomes and risk factors for failed trial of labor after cesarean delivery (TOLAC) in women with one previous cesarean section: a Chinese population-based study.

OBJECTIVE: To evaluate the outcomes and risk factors for trial of labor after cesarean delivery (TOLAC) failure in patients in China. METHODS: Consecutive patients who had a previous cesarean delivery (CD) and attempted TOLAC were included from 2014 to 2020. Patients who successfully delivered were classified into the TOLAC success group. Patients who attempted TOLAC but had a repeat CD due to medical issues were classified into the TOLAC failure group. Multiple logistic regression analyses were performed to examine the risk factors for TOLAC failure. RESULTS: In total, 720 women who had a previous CD and attempted TOLAC were identified and included. The success rate of TOLAC was 84.2%(606/720). Seven patients were diagnosed with uterine rupture, none of whom underwent hysterectomy. Multiple logistic regression analysis showed that the induction of labor (OR = 2.843, 95% CI: 1.571-5.145, P < 0.001) was positively associated with TOLAC failure, but the thickness of the lower uterine segment (LUS) (OR = 0.215, 95% CI: 0.103-0.448, P < 0.001) was negatively associated with TOLAC failure. CONCLUSIONS: This study suggested that TOLAC was effective in decreasing CD rates in the Chinese population. The induction of labor was positively associated with TOLAC failure, but the thickness of the LUS was negatively associated with TOLAC failure. Our findings need to be confirmed in larger samples with patients of different ethnicities.

LncRNA Mical2/miR-203a-3p sponge participates in epithelial-mesenchymal transition by targeting p66Shc in liver fibrosis.

Epithelial-mesenchymal transition (EMT) is regulated by reactive oxygen species (ROS) in liver fibrosis. p66Shc is a redox enzyme, but its role of EMT is unclear in liver fibrosis. Long noncoding RNAs (lncRNAs) have been implicated as important regulators in numerous physiological and pathological processes and generally acting as a microRNA (miRNA) sponge to regulate gene expression. The aim of the current study was to evaluate the contribution of p66Shc to EMT in liver fibrosis and the regulation of p66Shc by lncRNA sponge. In vivo, p66Shc silencing prevented carbon tetrachloride (CCl4)-induced EMT as evidenced by the upregulation of E-cadherin, downregulation of Vimentin and N-cadherin, and inhibition of oxidative stress and extracellular matrix (ECM) components. Moreover, in vitro, TGF-ß1 significantly enhanced ECM components, as well as the development of the EMT phenotype. These effects were abrogated by p66Shc downregulation and aggravated by p66Shc overexpression. Mechanistically, p66Shc contributed to EMT via mediating ROS, as evidenced by p66Shc downregulation inhibiting EMT under exogenous hydrogen peroxide (H2O2) stimulation. Furthermore, we found that molecule interacting with CasL2 (Mical2) lncRNA functioned as an endogenous miR-203a-3p sponge to regulate p66Shc expression. Both Mical2 silencing and miR-203a-3p agomiR treatment downregulated p66Shc expression, thus suppressing EMT in vivo and in vitro. Notably, the increased p66Shc and Mical2 levels and decreased miR-203a-3p levels in murine fibrosis were consistent with those in patients with liver fibrosis. In sum, our study reveals that p66Shc is critical for liver fibrosis and that Mical2, miR-203a-3p and p66Shc compose a novel regulatory pathway in liver fibrosis.

miR-103a-3p regulates mitophagy in Parkinson's disease through Parkin/Ambra1 signaling.

Parkin is a crucial protein that promotes the clearance of damaged mitochondria via mitophagy in neuron, and parkin mutations result in autosomal-recessive Parkinson's disease (AR-PD). However, the exact mechanisms underlying the regulation of Parkin-mediated mitophagy in PD remain unclear. In this study, PD models were generated through incubation of SH-SY5Y cells with 1-methyl-4-phenylpyridinium ion (MPP+, 1.5 mM for 24 h) and intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg for five consecutive days) in mice. A Bioinformatics database was used to identify Parkin-targeting microRNAs (miRNAs). Then, miR-103a-3p agomir, miR-103a-3p antagomir and Parkin siRNA were used to assess the effects of miR-103a-3p/Parkin/Ambra1 signaling-mediated mitophagy in PD in vitro and in vivo. The protein and mRNA levels of Parkin and Ambra1 were significantly decreased, while miR-103a-3p, which is a highly expressed miRNA in the human brain, was obviously increased in PD mouse and SH-SY5Y cell models. Moreover, miR-103a-3p suppressed Parkin expression by targeting a conserved binding site in the 3'-untranslated region (UTR) of Parkin mRNA. Importantly, miR-103a-3p inhibition resulted in neuroprotective effects and improved mitophagy in vitro and in vivo, whereas Parkin siRNA strongly abolished these effects. These findings suggested that miR-103a-3p inhibition has neuroprotective effects in PD, which may be involved in regulating mitophagy through the Parkin/Ambra1 pathway. Modulating miR-103a-3p levels may be an applicable therapeutic strategy for PD.

Effect of a new inhibitor of factor Xa zifaxaban, on thrombosis in the inferior vena cava in rabbits.

In recent years, oral factor Xa inhibitors have become a research focus as anticoagulant drugs. Zifaxaban is the first oral FXa inhibitor to enter clinical trials in China. The aim of this study was to determine the inhibitory effect of zifaxaban on thrombosisthrough a model ofinferior vena cava (IVC) thrombosis in rabbits. IVC thrombosis model was established by electrical injury and stenosis, and zifaxaban was administered (p.o.) for 5 consecutive days, then coagulation indicators and bleeding were observed. The results showed that zifaxaban had obvious inhibitory effects on FXa, and had a significant inhibitory effect on IVC thrombosis induced by electrical damage and stenosis. The effect of zifaxaban was similar to that of rivaroxaban, but the bleeding side-effects of zifaxaban were less severe than those of rivaroxaban. Zifaxaban could prolong the prothrombin time and activated partial thromboplastin time of plasma similar to that of other oral FXa inhibitors. Zifaxaban had a significant inhibitory effect on FXa, but it had no obvious effect on other coagulation factors, major anticoagulant factors or fibrinolytic indices. Our results suggest that zifaxaban had specific inhibitory effects on FXa and inhibited IVC thrombosis in rabbits with its hemorrhagic effect was less than that of rivaroxaban. Zifaxaban is ecpected to be developed as a new drug for the prevention of deep venous thrombosis, providing more medication options for patients with such disease, more research is required to support it in the future.

Uncaria rhynchophylla Ameliorates Parkinson's Disease by Inhibiting HSP90 Expression: Insights from Quantitative Proteomics.

BACKGROUND/AIMS: Uncaria rhynchophylla, known as "Gou-teng", is a traditional Chinese medicine (TCM) used to extinguish wind, clear heat, arrest convulsions, and pacify the liver. Although U. rhynchophylla has a long history of being often used to treat central nervous system (CNS) diseases, its efficacy and potential mechanism are still uncertain. This study investigated neuroprotective effect and the underlying mechanism of U. rhynchophylla extract (URE) in MPP+-induced SH-SY5Y cells and MPTP-induced mice. METHODS: MPP+-induced SH-SY5Y cells and MPTP-induced mice were used to established Parkinson's disease (PD) models. Quantitative proteomics and bioinformatics were used to uncover proteomics changes of URE. Western blotting was used to validate main differentially expressed proteins and test HSP90 client proteins (apoptosis-related, autophagy-related, MAPKs, PI3K, and AKT proteins). Flow cytometry and JC-1 staining assay were further used to confirm the effect of URE on MPP+-induced apoptosis in SH-SY5Y cells. Gait analysis was used to detect the behavioral changes in MPTP-induced mice. The levels of dopamine (DA) and their metabolites were examined in striatum (STR) by HPLC-EC. The positive expression of tyrosine hydroxylase (TH) was detected by immunohischemical staining and Western blotting. RESULTS: URE dose-dependently increased the cell viability in MPP+-induced SH-SY5Y cells. Quantitative proteomics and bioinformatics results confirmed that HSP90 was an important differentially expressed protein of URE. URE inhibited the expression of HSP90, which further reversed MPP+-induced cell apoptosis and autophagy by increasing the expressions of Bcl-2, Cyclin D1, p-ERK, p-PI3K p85, PI3K p110α, p-AKT, and LC3-I and decreasing cleaved caspase 3, Bax, p-JNK, p-p38, and LC3-II. URE also markedly decreased the apoptotic ratio and elevated mitochondrial transmembrane potential (DΨm). Furthermore, URE treatment ameliorated behavioral impairments, increased the contents of DA and its metabolites and elevated the positive expressions of TH in SN and STR as well as the TH protein. CONCLUSIONS: URE possessed the neuroprotective effect in vivo and in vitro, regulated MAPK and PI3K-AKT signal pathways, and inhibited the expression of HSP90. U. rhynchophylla has potentials as therapeutic agent in PD treatment.

Salvianolic acid A alleviates chronic ethanol-induced liver injury via promotion of ß-catenin nuclear accumulation by restoring SIRT1 in rats.

In recent years, alcoholic liver disease (ALD) has emerged as a growing public health problem worldwide. ß-catenin plays an important role in the growth, development, regeneration and metabolic activity of the liver. Salvianolic acid A (SalA) is a water-soluble component from the root extract of Salvia miltiorrhiza Bunge, and its effect on ALD has not yet been investigated. This study aimed to investigate the effect of SalA on chronic alcohol-induced liver injury and to explore the role of SIRT1-mediated ß-catenin deacetylation in such an effect. In this study, SalA treatment significantly alleviated the accumulation of lipid droplets and reduced the plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), alcohol and ammonia levels in rats. SalA enhanced ethanol and ammonia metabolism and maintained mitochondrial homeostasis. Moreover, SalA restored the activity of the major ethanol-metabolizing enzymes and oxidative stress functions in the liver. Importantly, we found that SalA treatment effectively inhibited the ethanol-mediated decrease in nuclear ß-catenin by upregulating SIRT1 in the liver. SIRT1 then deacetylated ß-catenin to promote its accumulation in the nucleus, thereby preventing alcohol-induced liver injury. The results demonstrate that the SIRT1/ß-catenin pathway is a key therapeutic target in liver injury caused by chronic alcohol exposure and that SalA protects against alcohol-induced liver injury via the SIRT1-mediated deacetylation of ß-catenin.

Long-term survival and late complications of intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma.

BACKGROUND: To evaluate the effectiveness and toxicities of intensity-modulated radiotherapy (IMRT) for locally recurrent nasopharyngeal carcinoma (NPC). METHODS: One hundred and eighty-four previously irradiated NPC patients with recurrent disease and re-irradiated by IMRT between February 2005 to May 2013 had been reviewed. The disease was re-staged I in 33, II in 27, III in 70 and IV in 54 patients. Seventy-five percent of the patients received cisplatin-based chemotherapy. RESULTS: The median survival time was 33 months. The 3-year actuarial rates of local recurrence-free survival (LRFS), distant metastases-free survival (DMFS), and overall survival (OS) rates were 85.1, 91.1, and 46.0%, respectively. About 53% of the patients experienced Grade 3-4 late toxicities. Forty-four patients died of massive hemorrhage of the nasopharynx caused by radiation induced mucosal necrosis. Multivariate analysis indicated that chemotherapy and time interval between initial radiotherapy and re-irradiation were independent predictors for DMFS. CONCLUSION: IMRT is an effective method for patients with locally recurrent NPC. Massive hemorrhage of the nasopharynx is the major sever late complication and also the leading cause of death. Early recurrence is negative factor for DMFS. Combination of chemotherapy can improve DMFS, but not for OS. Optimal salvage treatment strategies focusing on improvement of survival and minimization of late toxicities are warranted.

Carnosol-mediated Sirtuin 1 activation inhibits Enhancer of Zeste Homolog 2 to attenuate liver fibrosis.

Quiescent hepatic stellate cell (HSC) activation and subsequent conversion into myofibroblasts is the central event in hepatic fibrosis pathogenesis. Epithelial-mesenchymal transition (EMT), another vital participant in liver fibrosis, has the potential to initiate HSC activation, which promotes abundant myofibroblast production. Previous studies suggest that Enhancer of Zeste Homolog 2 (EZH2) plays a significant role in myofibroblast transdifferentiation; however, the underlying mechanisms remain largely unaddressed. Carnosol (CS), a compound extracted from rosemary, displays multiple pharmacological activities. This study aimed to investigate the signaling mechanisms underlying EZH2 inhibition and the anti-fibrotic effect of CS in liver fibrosis. We found that CS significantly inhibited CCl4- and TGFß1-induced liver fibrosis and reduced both HSC activation and EMT. EZH2 knockdown also prevented these processes induced by TGFß1 in HSCs and AML-12 cells. Interestingly, the protective effect of CS was positively associated with Sirtuin 1 (SIRT1) activation and accompanied by EZH2 inhibition. SIRT1 knockdown attenuated the EZH2 inhibition induced by CS and increased EZH2 acetylation, which enhanced its stability. Conversely, upon TGFß1 exposure, SIRT1 activation significantly reduced the level of EZH2 acetylation; however, EZH2 overexpression prevented the SIRT1 activation that primed myofibroblast inhibition, indicating that EZH2 is a target of SIRT1. Thus, SIRT1/EZH2 regulation could be used as a new therapeutic strategy for fibrogenesis. Together, this study provides evidence of activation of the SIRT1/EZH2 pathway by CS that inhibits myofibroblast generation, and thus, CS may represent an attractive candidate for anti-fibrotic clinical therapy.

Carnosic acid protects non-alcoholic fatty liver-induced dopaminergic neuron injury in rats.

Non-alcoholic fatty liver disease (NAFLD) has been reported to induce cognitive impairments of hippocampus and may influence central nervous system. In the present study, we investigated whether carnosic acid (CA) ameliorates dopaminergic neuron injury in a rat model of NAFLD. In order to induce NAFLD, rats were fed with high-fat diet (HFD) for 10 weeks. We found that continued CA administration reduced lipid accumulation marked by decreases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, and an increase in high-density lipoprotein cholesterol (HDL-C) level in the serum. H&E staining revealed that feeding CA reduced lipid droplets accumulation, and alleviated oxidative stress by increasing in superoxide dismutase (SOD) level and decreasing in malondialdehyde (MDA) level in the liver. In addition, by measuring several parameters of gait analysis, we demonstrated that CA treatment ameliorated behavioral impairments, as evidenced by decreased duration and maximum variation, accompanied by increased average speed and cadence. Furthermore, CA treated-animals displayed an increase in the contents of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacelic acid (DOPAC) and elevated the expressions of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) as well as the TH protein in the striatum. Together, these findings suggest that CA may be an effective agent in protecting rats from NAFLD-induced dopaminergic neuron injury.

Procaterol but not dexamethasone protects 16HBE cells from H2O2-induced oxidative stress.

Oxidative stress is an important pathophysiological factor of asthma and chronic obstructive pulmonary disease (COPD). We hypothesized that procaterol and dexamethasone might treat inflammation through inhibiting oxidative stress in vitro. This study evaluated procaterol and dexamethasone in the hydrogen peroxide (H2O2)-induced immortal human bronchial epithelial cell model of oxidative stress and investigated the underlying mechanisms. Results showed that exposure to 125 µM H2O2 for 2 h led to a 50% reduction in the cell viability, significantly increased the percentage of apoptosis, and elevated levels of malondialdehyde and reactive oxygen species. Pretreatment with procaterol (25 - 200 nM) could reduce these effects in a dose-dependent manner. In contrast, pretreatment with dexamethasone (100 nM, 1000 nM) was inefficient. Pretreatment with procaterol plus dexamethasone (100 nM procaterol + 1000 nM dexamethasone) was effective, but the combined effect was not more effective than the sole pretreatment with 100 nM procaterol. The nuclear factor kappa-B (NF-κB) pathway was involved in the pathogenic mechanisms of H2O2. Procaterol may indirectly inhibit H2O2-induced activation of the NF-κB pathway due to its capability of antioxidation. Glucocorticoids may be not recommended to treat asthma or COPD complicated with severe oxidative stress.

Preliminary results of nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: a retrospective study of 364 patients.

The aim of the study was to evaluate the survival and toxicity of 364 patients with nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT). Cisplatin-based chemotherapy was given to patients with local-regionally advanced disease. The median follow-up was 26 months (range 3-62 months). The 2-year local failure-free survival, regional failure-free survival (RFFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 97.6, 96.8, 89.1 and 93.5 %, respectively. Overall disease failures (at any site) were found in 60 patients. Eighteen patients experienced locoregional failures: seven were local only, seven were regional only and four were both local and regional. Forty-two patients developed distant metastases. Of these, 30 patients had single organ metastasis and 12 had multiple organ metastases. The most common acute toxicities were dermatitis, mucositis and xerostomia. Grade 0-2 dermatitis, mucositis and xerostomia occurred in 337 patients (92.6 %), 204 patients (56.1 %) and 364 patients (100 %), respectively. Grade 3 dermatitis, mucositis and xerostomia were seen in 27 patients (7.4 %), 160 patients (44 %) and 0 patients. No Grade 4 acute toxicities were observed. N stage was an independent prognostic factor for RFFS, DMFS and OS. Our preliminary results showed that IMRT provides excellent local-regional control for NPC, with acceptable acute toxicities. Distant metastasis remains the most difficult treatment challenge. More effective systemic chemotherapy should be explored.

Insights into the defensive roles of lncRNAs during Mycoplasma pneumoniae infection.

Mycoplasma pneumoniae causes respiratory tract infections, affecting both children and adults, with varying degrees of severity ranging from mild to life-threatening. In recent years, a new class of regulatory RNAs called long non-coding RNAs (lncRNAs) has been discovered to play crucial roles in regulating gene expression in the host. Research on lncRNAs has greatly expanded our understanding of cellular functions involving RNAs, and it has significantly increased the range of functions of lncRNAs. In lung cancer, transcripts associated with lncRNAs have been identified as regulators of airway and lung inflammation in a process involving protein complexes. An excessive immune response and antibacterial immunity are closely linked to the pathogenesis of M. pneumoniae. The relationship between lncRNAs and M. pneumoniae infection largely involves lncRNAs that participate in antibacterial immunity. This comprehensive review aimed to examine the dysregulation of lncRNAs during M. pneumoniae infection, highlighting the latest advancements in our understanding of the biological functions and molecular mechanisms of lncRNAs in the context of M. pneumoniae infection and indicating avenues for investigating lncRNAs-related therapeutic targets.

Treatment responses of procaterol and CD38 inhibitors in an ozone-induced airway hyperresponsiveness mice model.

Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of many respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). To evaluate the treatment responses of procaterol and CD38 inhibitors in an ozone-induced AHR mice model, we hypothesized that procaterol and two synthetic CD38 inhibitors (Compounds T and H) might have therapeutic effects on the ozone-induced AHR mice model, and the nuclear factor-kappaB (NF-κB) pathway and the CD38 enzymatic activity might be involved in the mechanisms. With the exception of the Control group, ozone exposure was used to establish an AHR model. Male Kunming mice in the Procaterol and CD38 inhibitors groups were treated with an emulsifier of procaterol hydrochloride, Compound T or H. Results indicated that (1) no drug showed severe toxicity in this study; (2) ozone exposure induced airway inflammation and AHR; (3) intragastric treatment with procaterol and Compound T achieved potent therapeutic effects, but Compound H did not show any therapeutic effect; (4) the NF-κB pathway was involved in both the pathogenic mechanisms of ozone and therapeutic mechanisms of procaterol and Compound T; (5) however, the in vivo effect of Compound T was not caused by its inhibitory activity on CD38. Taken together, procaterol and Compound T are potentially good drugs to treat asthma and COPD complicated with ozone exposure.

Experience with combination of docetaxel, cisplatin plus 5-fluorouracil chemotherapy, and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: Our aim was to evaluate the efficacy and toxicity of cisplatin, fluorouracil, and docetaxel chemotherapy plus intensity-modulated radiotherapy (IMRT) for locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS: Sixty patients with locoregionally advanced NPC were enrolled. Patients received IMRT plus three courses of neoadjuvant chemotherapy and two courses of adjuvant chemotherapy consisting of docetaxel (60 mg/m(2)/day on day 1), cisplatin (25 mg/m(2)/day on days 1-3), and 5-fluorouracil (500 mg/m(2)/day on days 1-3). RESULTS: The overall response rate to neoadjuvant chemotherapy was 89 %. Three months after the completion of radiotherapy, 53 (93 %) patients achieved complete regression, 3 (5 %) achieved partial response (PR), and 1 experienced liver metastasis. However, among the 3 PR patients, 2 patients had no evidence of relapse in the follow-up. With a median follow-up of 27 months (range, 6-43), the 2-year estimated locoregional failure-free survival, distant failure-free survival, progression-free survival, and overall survival were 96.6, 93.3, 89.9, and 98.3 %, respectively. Leukopenia was the main adverse effect in chemotherapy; 14 patients experienced grade 3 or grade 4 neutropenia, and 1 patient developed febrile neutropenia. The nonhematological adverse events included alopecia, nausea, vomiting, anorexia, and diarrhea. The incidence of grade 3 acute radiotherapy-related mucositis was 28.3 %; no grade 4 acute mucositis was observed. No grade 3 or grade 4 hematological toxicity occurred during radiotherapy. None of the patients had interrupted radiotherapy. The common late adverse effects included xerostomia and hearing impairment. CONCLUSIONS: Neoadjuvant-adjuvant chemotherapy using cisplatin, fluorouracil, plus docetaxel combined with IMRT was an effective and well-tolerated alternative for advanced NPC.

Salvianolic Acid A Protects against Acetaminophen-Induced Hepatotoxicity via Regulation of the miR-485-3p/SIRT1 Pathway.

The vast majority of drug-induced liver injury is mainly attributed to acetaminophen (APAP) overdose. Salvianolic acid A (Sal A), a powerful water-soluble compound obtained from Salvia miltiorrhiza, has been confirmed to exert hepatoprotective effects. However, the beneficial effects and the exact mechanisms of Sal A on APAP-induced hepatotoxicity remain unclear. In this study, APAP-induced liver injury with or without Sal A treatment was examined in vitro and in vivo. The results showed that Sal A could alleviate oxidative stress and inflammation by regulating Sirtuin 1 (SIRT1). Furthermore, miR-485-3p could target SIRT1 after APAP hepatotoxicity and was regulated by Sal A. Importantly, inhibiting miR-485-3p had a hepatoprotective effect similar to that of Sal A on APAP-exposed AML12 cells. These findings suggest that regulating the miR-485-3p/SIRT1 pathway can alleviate oxidative stress and inflammation induced by APAP in the context of Sal A treatment.

A non-thermal modification method to promote the interaction of zein-alginate oligosaccharides composites for better encapsulation and stability-Cold plasma.

This current research explored the application of cold plasma (CP) treatment to modify zein-alginate oligosaccharide (zein-AOS) composites in an ethanol-water solution. Anti-solvent method was used to prepare zein-AOS nanoparticles (NPs), and the objective was to investigate the mechanism by which CP promotes interaction between protein and saccharides. Characterization results indicated that CP treatment improved hydrogen bonding and electrostatic interaction between zein and AOS. The CP zein-AOS NPs underwent dispersion and rearrangement, resulting in smaller aggregates with better dispersibility. Among the various induction conditions tested, the zein-AOS85 NPs (induced at 85 W for 2 min) exhibited superior performance as delivery wall materials, with smaller particle size (234.67 nm), larger specific surface area (9.443 m2/g), and higher surface charge (-35.43 mV). In addition, zein-AOS85 showed high stability when used as delivery wall material, providing more binding sites and self-assembly dynamics for nutrients. Curcumin was used as the nutrient model in this study, and CP was found to enhance hydrogen bonding, electrostatic interaction, and hydrophobic interaction between zein, AOS, and nutrients, resulting in increased encapsulation efficiency (EE) from 63.80 % to 85.17 %. The delivery system also exhibited good pH, ionic strength, storage, and dispersion stability.