Methylprednisolone alleviates cognitive functions through the regulation of neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and linked to abnormal deposition of amyloid-ß (Aß), neurofibrillary tangles (NFTs), synaptic dysfunction, and neuroinflammation. Despite significant progress in unravelling the pathogenesis of AD, currently main therapeutic interventions is limited to symptomatic alleviation. Methylprednisolone (MP), a synthetic glucocorticoid, is recognized for its extensive anti-inflammatory properties. Our study assessed the neuroprotective effect of MP (25 mg/kg) administration to an Aß1-42-induced AD mouse model. Our findings demonstrate that MP treatment can ameliorate cognitive impairment in Aß1-42-induced AD mice and suppress microglial activation in the cortex and hippocampus. RNA-Sequencing analysis reveals that MP ultimately rescues cognitive dysfunction through improving the synapse function and inhibiting the immune and inflammatory processes. Our study suggests that MP could be a promising drug alternative for the treatment of AD, either alone or in combination with other existing drugs.

Community pharmacy personnel interventions for smoking cessation.

BACKGROUND: Community pharmacists could provide effective smoking cessation treatment because they offer easy access to members of the community. They are well placed to provide both advice on the correct use of smoking cessation products and behavioural support to aid smoking cessation. OBJECTIVES: To assess the effectiveness of interventions delivered by community pharmacy personnel to assist people to stop smoking, with or without concurrent use of pharmacotherapy. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register, along with clinicaltrials.gov and the ICTRP, for smoking cessation studies conducted in a community pharmacy setting, using the search terms pharmacist* or pharmacy or pharmacies. Date of the most recent search: January 2019. SELECTION CRITERIA: Randomised controlled trials of interventions delivered by community pharmacy personnel to promote smoking cessation amongst their clients who were smokers, compared with usual pharmacy support or any less intensive programme. The main outcome measure was smoking cessation rates at six months or more after the start of the intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane for study screening, data extraction and management. We conducted a meta-analysis using a Mantel-Haenszel random-effects model to generate risk ratios (RRs) and 95% confidence intervals (CIs). MAIN RESULTS: We identified seven studies including 1774 participants. We judged three studies to be at high risk of bias and four to be at unclear risk. Each study provided face-to-face behavioural support delivered by pharmacy staff, and required pharmacy personnel training. Typically such programmes comprised support starting before quit day and continuing with weekly appointments for several weeks afterwards. Comparators were either minimal or less intensive behavioural support for smoking cessation, typically comprising a few minutes of one-off advice on how to quit. Participants in both intervention and control arms received equivalent smoking cessation pharmacotherapy in all but one study. All studies took place in high-income countries, and recruited participants visiting pharmacies. We pooled six studies of 1614 participants and detected a benefit of more intensive behavioural smoking cessation interventions delivered by community pharmacy personnel compared with less intensive cessation interventions at longest follow-up (RR 2.30, 95% CI 1.33 to 3.97; I2 = 54%; low-certainty evidence). AUTHORS' CONCLUSIONS: Community pharmacists can provide effective behavioural support to people trying to stop smoking. However, this conclusion is based on low-certainty evidence, limited by risk of bias and imprecision. Further research could change this conclusion.

Ad-HGF improves the cardiac remodeling of rat following myocardial infarction by upregulating autophagy and necroptosis and inhibiting apoptosis.

Cell death in MI is the most critical determinant of subsequent left ventricular remodeling and heart failure. Besides apoptosis, autophagy and necroptosis have been recently found to be another two regulated cell death styles. HGF has been reported to have a protective role in MI, but its impact on the three death styles remains unclear. Thus, our study was performed to investigate the distribution of autophagy, apoptosis and necroptosis in cardiac tissues after MI and explore the role and mechanism of Ad-HGF on cardiac remodeling by regulating the three death styles. We firstly showed the distribution of autophagy, apoptosis and necroptosis differs in temporal and spatial context after MI using immunofluorescence. Notably, Ad-HGF treatment improves the cardiac remodeling of SD rats following MI by preserving the heart function, reducing the scar size and aggresomes. Further mechanism study reveals Ad-HGF promotes autophagy and necroptosis and inhibits apoptosis in vivo and in vitro. Co-immunoprecipitation assays showed Ad-HGF treatment significantly decreased the binding of Bcl-2 to Beclin1 but enhanced Bcl-2 binding to Bax in H9c2 cells under hypoxia. Moreover, HGF-induced sequestration of Bax by Bcl-2 allows Bax to become inactive, thereby inhibiting apoptosis. In addition, Ad-HGF markedly increased the formation of Beclin1-Vps34-Atg14L complex, which accounted for promoting autophagy. Both the western blot and activity assay showed Ad-HGF significantly decreased the caspase 8 protein and activity levels, which obligated the cell to undergo necroptosis under hypoxia and block apoptosis. Thus, our findings offer new evidence and strategies for the treatment of MI and post-MI cardiac remodeling.

Diphenylarsinic acid contaminated soil remediation by titanium dioxide (P25) photocatalysis: Degradation pathway, optimization of operating parameters and effects of soil properties.

Diphenylarsinic acid (DPAA) is formed during the leakage of arsenic chemical weapons in sites and poses a high risk to biota. However, remediation methods for DPAA contaminated soils are rare. Here, the photocatalytic oxidation (PCO) process by nano-sized titanium dioxide (TiO2) was applied to degrade DPAA in soil. The degradation pathway was firstly studied, and arsenate was identified as the final product. Then, an orthogonal array experimental design of L9(3)(4), only 9 experiments were needed, instead of 81 experiments in a conventional one-factor-at-a-time, was used to optimize the operational parameters soil:water ratio, TiO2 dosage, irradiation time and light intensity to increase DPAA removal efficiency. Soil:water ratio was found to have a more significant effect on DPAA removal efficiency than other properties. The optimum conditions to treat 4 g soil with a DPAA concentration of 20 mg kg(-1) were found to be a 1:10 soil: water ratio, 40 mW cm(-2) light intensity, 5% TiO2 in soil, and a 3-hour irradiation time, with a removal efficiency of up to 82.7%. Furthermore, this method (except for a change in irradiation time from 3 to 1.5h) was validated in nine different soils and the removal efficiencies ranged from 57.0 to 78.6%. Removal efficiencies were found to be negatively correlated with soil electrical conductivity, organic matter content, pH and total phosphorus content. Finally, coupled with electron spin resonance (ESR) measurement, these soil properties affected the generation of OH• by TiO2 in soil slurry. This study suggests that TiO2 photocatalytic oxidation is a promising treatment for removing DPAA from soil.

[Photo-catalytical degradation of diphenylarsinic acid by TiO2 (P25)].

Diphenylarsinic acid (DPAA) is the major contaminant in environment polluted by abandoned chemical weapons. DPAA poses high risks to biota but remediation methods for this contaminant are rare. Previous research showed DPAA could be degraded within a short time by TiO2 (P25). Here the kinetics of DPAA degradation catalyzed by P25 was studied. Results showed the photo-catalytical degradation of DPAA by P25 consisted of two processes: adsorption and photo-reaction. The whole reaction could be fitted by Langmuir-Hinshelwood kinetics. Variation in pH and ionic strength caused change in adsorption of DPAA onto the TiO2 catalyst, which led to the change of reaction rate, showing a decreasing trend with the decreasing adsorption amount of DPAA. Dissolved oxygen promoted the catalytical degradation of DPAA by TiO2, and the hydroxyl free radical played the most important role in the photodegradation of DPAA, which was testified through quenching experiments with free radical scanvengers.

Protective effect of AVS073, a polyherbal formula, against UVA-induced melanogenesis through a redox mechanism involving glutathione-related antioxidant defense.

BACKGROUND: Ayurved Siriraj Brand Wattana formula (AVS073), a Thai herbal formula, has traditionally been used for health promotion and prevention of age-related problems. Ultraviolet A (UVA) is recognized to play a vital role in stimulation of melanin synthesis responsible for abnormal skin pigmentation possibly mediated by photooxidative stress. We thus aimed to study the inhibitory effect of AVS073 extracts on UVA-induced melanogenesis via a redox mechanism involving glutathione (GSH) synthesis and glutathione S-transferase (GST) using human melanoma (G361) cell culture. METHODS: The standardization of AVS073 extracts was carried out by TLC and UHPLC to obtain fingerprinting profiles of the formula, which identified several phenolic compounds including gallic acid (GA) in the formula. Antimelanogenic actions of AVS073 (up to 60 µg/ml) and GA (up to 10 µg/ml) were investigated by measuring tyrosinase activity and mRNA as well as melanin level in G361 cells irradiated with UVA. Moreover, antioxidant actions of the herbal formula and GA were determined by evaluating oxidant formation and modulation of GSH-related antioxidant defenses including GSH content, GST activity and mRNA level of γ-glutamate cysteine ligase catalytic (γ-GCLC) and modifier (γ-GCLM) subunit and GST. RESULTS: AVS073 extracts and GA, used as a reference compound, suppressed UVA-augmented tyrosinase activity and mRNA and melanin formation. In addition, pretreatment with AVS073 and GA was able to inhibit cellular oxidative stress, GSH depletion, GST inactivation and downregulation of γ-GCLC, γ-GCLM and GST mRNA in G361 cells exposed to UVA radiation. CONCLUSIONS: AVS073 formula exerted antimelanogenic effects possibly through improving the redox state by upregulation of GSH and GST. Moreover, pharmacological activity of the polyherbal formula would be attributed to combined action of different phenolic compounds present in the formula.

Current and emerging pharmacotherapeutic options for smoking cessation.

Tobacco smoking remains the single most preventable cause of morbidity and mortality in developed countries and poses a significant threat across developing countries where tobacco use prevalence is increasing. Nicotine dependence is a chronic disease often requiring multiple attempts to quit; repeated interventions with pharmacotherapeutic aids have become more popular as part of cessation therapies. First-line medications of known efficacy in the general population include varenicline tartrate, bupropion hydrochloride, nicotine replacement therapy products, or a combination thereof. However, less is known about the use of these products in marginalized groups such as the indigenous, those with mental illnesses, youth, and pregnant or breastfeeding women. Despite the efficacy and safety of these first line pharmacotherapies, many smokers continue to relapse and alternative pharmacotherapies and cessation options are required. Thus, the aim of this review is to summarize the existing and developing pharmacotherapeutic and other options for smoking cessation, to identify gaps in current clinical practice, and to provide recommendations for future evaluations and research.

[Role of P38-MAPK signal transduction pathway and effect of panax notoginoside in rats with hypoxic hypercapnia pulmonary hypertension].

OBJECTIVE: To investigate the role and significance of P38-MAPK in the pathological process of hypoxic hypercapnia pulmonary hypertension in rats, and the protection of panax notoginoside (PNS). METHODS: (1) To set up rat pathological model of hypoxic hypercapnia pulmonary hypertension: seventy two male SD rats (200 280 g) were randomly divided into six groups (n = 12), which were normal group (N group), hypoxic hypercapnia for 3-day group (H3d), hypoxic hypercapnia for 1-week group(H1w), hypoxic hypercapnia for 2-week group (H2w), hypoxic hypercapnia for 4-week group (H4w) and PNS-injected group (Hp). The rats of PNS -injected group were injected PNS before being placed in the chamber (50 mg/(kg x d), ip), and other groups were injected normal sodium (2 ml/kg, ip). (2) The shapes of pulmonary artery were detected by HE staining. (3) Western blot was used to study the protein expression of p38-MAPK. The expression of p38-MAPK in lung tissue and pulmonary blood vessel was investigated by immunohistochemistry. RESULTS: (1) The ratio of vessel wall area/total area (WA/ TA) in H1w, H2w, H4w and Hp group was higher than that of N group (P < 0.05), but that of H3d group did not change obviously (P > 0. 05 vs N group). The ratio of WA/TA in Hp group was obviously lower than that of H4w, group (P < 0.05). (2) The levels of P-p38 protein was markedly ascended in H3d group (0.225 +/- 0.071) compared with N group (0.012 +/- 0.006), and expression of P-p38 protein was significantly positive in H1w, H2w, H4w groups. (P < 0.05). (3) As P-p38 protein in pulmonary arterial tunica intima and tunica media, sterile expression in N group (0.099 +/- 0.015) and H3d group (0.107 +/- 0.013) contrasted to H4w group (0.124 +/- 0.025, P < 0.05), then tended to rise in H2w, H4w group (P < 0.05). (4) In pulmonary tissue, the levels of P-p38 protein in PNS-injected group were lower 53.02% (P < 0.05) than those in H4w group. In pulmonary arterial tunica intima and tunica media the levels of P-p38 protein in PNS-injected group were lower 87.33% (P < 0.05) than those in H4w group. CONCLUSION: p38-MAPK as a signal transduction may play an important role in the development of hypoxia induced pulmonary hypertension. The effect of PNS on reducing pulmonary hypertension and improving pulmonary vascular wall remodeling may be related to its inhibiting expression of p38 MAPK.

Role of P38-MAPK signal transduction pathway and effect of panax notoginoside in rats with hypoxic hypercapnia pulmonary hypertension / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the role and significance of P38-MAPK in the pathological process of hypoxic hypercapnia pulmonary hypertension in rats, and the protection of panax notoginoside (PNS).</p><p><b>METHODS</b>(1) To set up rat pathological model of hypoxic hypercapnia pulmonary hypertension: seventy two male SD rats (200 280 g) were randomly divided into six groups (n = 12), which were normal group (N group), hypoxic hypercapnia for 3-day group (H3d), hypoxic hypercapnia for 1-week group(H1w), hypoxic hypercapnia for 2-week group (H2w), hypoxic hypercapnia for 4-week group (H4w) and PNS-injected group (Hp). The rats of PNS -injected group were injected PNS before being placed in the chamber (50 mg/(kg x d), ip), and other groups were injected normal sodium (2 ml/kg, ip). (2) The shapes of pulmonary artery were detected by HE staining. (3) Western blot was used to study the protein expression of p38-MAPK. The expression of p38-MAPK in lung tissue and pulmonary blood vessel was investigated by immunohistochemistry.</p><p><b>RESULTS</b>(1) The ratio of vessel wall area/total area (WA/ TA) in H1w, H2w, H4w and Hp group was higher than that of N group (P < 0.05), but that of H3d group did not change obviously (P > 0. 05 vs N group). The ratio of WA/TA in Hp group was obviously lower than that of H4w, group (P < 0.05). (2) The levels of P-p38 protein was markedly ascended in H3d group (0.225 +/- 0.071) compared with N group (0.012 +/- 0.006), and expression of P-p38 protein was significantly positive in H1w, H2w, H4w groups. (P < 0.05). (3) As P-p38 protein in pulmonary arterial tunica intima and tunica media, sterile expression in N group (0.099 +/- 0.015) and H3d group (0.107 +/- 0.013) contrasted to H4w group (0.124 +/- 0.025, P < 0.05), then tended to rise in H2w, H4w group (P < 0.05). (4) In pulmonary tissue, the levels of P-p38 protein in PNS-injected group were lower 53.02% (P < 0.05) than those in H4w group. In pulmonary arterial tunica intima and tunica media the levels of P-p38 protein in PNS-injected group were lower 87.33% (P < 0.05) than those in H4w group.</p><p><b>CONCLUSION</b>p38-MAPK as a signal transduction may play an important role in the development of hypoxia induced pulmonary hypertension. The effect of PNS on reducing pulmonary hypertension and improving pulmonary vascular wall remodeling may be related to its inhibiting expression of p38 MAPK.</p>

Inhibition of UVA-mediated melanogenesis by ascorbic acid through modulation of antioxidant defense and nitric oxide system.

Ascorbic acid (AA) has been well known as a skin whitening agent, although attempts have been made to evaluate its protective role against ultraviolet (UV)-induced skin hyperpigmentation or increased melanin production. While melanogenesis is a defense mechanism of the skin against UV irradiation, melanin overproduction may also contribute to melanoma initiation. UVA might play a role in melanogenesis through promoting oxidative stress, which occurs as the result of increased formation of oxidants and/or reactive nitrogen species (RNS) including nitric oxide (NO). Therefore, we investigated the antimelanogenic effect of AA (7.5-120 µM) in association with its inhibitory effect on UVA-induced oxidant formation, NO production through endothelial and inducible NO synthases (eNOS and iNOS) activation and impairment of antioxidant defense using G361 human melanoma cells. Our study demonstrated a comparable ability of AA with that of kojic acid, a well-known tyrosinase inhibitor in inhibiting mushroom tyrosinase. Melanin content was reduced by AA, but neither tyrosinase activity nor mRNA levels were reduced by AA at non-cytotoxic concentrations in UVA-irradiated G361 cells. AA was shown to inhibit UVA-mediated catalase (CAT) inactivation, glutathione (GSH) depletion, oxidant formation and NO production through suppression of eNOS and iNOS mRNA. We report herein that AA can protect against UVA-dependent melanogenesis possibly through the improvement of antioxidant defense capacity and inhibition of NO production through down-regulation of eNOS and iNOS mRNA.

[Spectroscopic study of photocatalytic mechanism of methanol and CO2].

Ni-Ti-O/SiO2 catalyst was prepared by impregnation method, and its photocatalytic performance for carbonylation of methanol with CO2 was investigated under UV light. The in-situ IR, XPS and MS were carried out to analyze the possible photocatalytic reaction mechanism. Results indicated that the Ni-Ti-O/SiO2 exhibited good photocatalytic performance for carbonylation of methanol with CO2, the methanol conversion reached up to 24.9%, and the selectivity for the carbonylated products was more than 60% within 180 min reaction time. The catalyst characterization results showed that the O==C .--O- and CH3OC(O)* might be important intermediate in the carbonylation of methanol with CO2.

Soil respiration in relation to photosynthesis of Quercus mongolica trees at elevated CO2.

Knowledge of soil respiration and photosynthesis under elevated CO(2) is crucial for exactly understanding and predicting the carbon balance in forest ecosystems in a rapid CO(2)-enriched world. Quercus mongolica Fischer ex Ledebour seedlings were planted in open-top chambers exposed to elevated CO(2) (EC = 500 µmol mol(-1)) and ambient CO(2) (AC = 370 µmol mol(-1)) from 2005 to 2008. Daily, seasonal and inter-annual variations in soil respiration and photosynthetic assimilation were measured during 2007 and 2008 growing seasons. EC significantly stimulated the daytime soil respiration by 24.5% (322.4 at EC vs. 259.0 mg CO(2) m(-2) hr(-1) at AC) in 2007 and 21.0% (281.2 at EC vs. 232.6 mg CO(2) m(-2) hr(-1) at AC) in 2008, and increased the daytime CO(2) assimilation by 28.8% (624.1 at EC vs. 484.6 mg CO(2) m(-2) hr(-1) at AC) across the two growing seasons. The temporal variation in soil respiration was positively correlated with the aboveground photosynthesis, soil temperature, and soil water content at both EC and AC. EC did not affect the temperature sensitivity of soil respiration. The increased daytime soil respiration at EC resulted mainly from the increased aboveground photosynthesis. The present study indicates that increases in CO(2) fixation of plants in a CO(2)-rich world will rapidly return to the atmosphere by increased soil respiration.