Impact of large scale, multicomponent intervention to reduce proton pump inhibitor overuse in integrated healthcare system: difference-in-difference study.

OBJECTIVE: To determine how a large scale, multicomponent, pharmacy based intervention to reduce proton pump inhibitor (PPI) overuse affected prescribing patterns, healthcare utilization, and clinical outcomes. DESIGN: Difference-in-difference study. SETTING: US Veterans Affairs Healthcare System, in which one regional network implemented the overuse intervention and all 17 others served as controls. PARTICIPANTS: All individuals receiving primary care from 2009 to 2019. INTERVENTION: Limits on PPI refills for patients without a documented indication for long term use, voiding of PPI prescriptions not recently filled, facilitated electronic prescribing of H2 receptor antagonists, and education for patients and clinicians. MAIN OUTCOME MEASURES: The primary outcome was the percentage of patients who filled a PPI prescription per 6 months. Secondary outcomes included percentage of days PPI gastroprotection was prescribed in patients at high risk for upper gastrointestinal bleeding, percentage of patients who filled either a PPI or H2 receptor antagonist prescription, hospital admission for acid peptic disease in older adults appropriate for PPI gastroprotection, primary care visits for an upper gastrointestinal diagnosis, upper endoscopies, and PPI associated clinical conditions. RESULTS: The number of patients analyzed per interval ranged from 192 607 to 250 349 in intervention sites and from 3 775 953 to 4 360 868 in control sites, with 26% of patients receiving PPIs before the intervention. The intervention was associated with an absolute reduction of 7.3% (95% confidence interval -7.6% to -7.0%) in patients who filled PPI prescriptions, an absolute reduction of 11.3% (-12.0% to -10.5%) in PPI use among patients appropriate for gastroprotection, and an absolute reduction of 5.72% (-6.08% to -5.36%) in patients who filled a PPI or H2 receptor antagonist prescription. No increases were seen in primary care visits for upper gastrointestinal diagnoses, upper endoscopies, or hospital admissions for acid peptic disease in older patients appropriate for gastroprotection. No clinically significant changes were seen in any PPI associated clinical conditions. CONCLUSIONS: The multicomponent intervention was associated with reduced PPI use overall but also in patients appropriate for gastroprotection, with minimal evidence of either clinical benefits or harms.

Analysis of the regulatory mechanism of exogenous IAA-mediated tryptophan accumulation and synthesis of endogenous IAA in Chlorococcum humicola.

The activated sludge method is widely used for the treatment of phenol-containing wastewater, which gives rise to the problem of toxic residual sludge accumulation. Indole-3-acetic acid (IAA), a typical phytohormone, facilitates the microalgal resistance to toxic inhibition while promoting biomass accumulation. In this study, Chlorococcum humicola (C. humicola) was cultured in toxic sludge extract and different concentrations of IAA were used to regulate its physiological properties and enrichment of high value-added products. Ultimately, proteomics analysis was used to reveal the response mechanism of C. humicola to exogenous IAA. The results showed that the IAA concentration of 5 × 10-6 mol/L (M) was most beneficial for C. humicola to cope with the toxic stress in the sludge extract medium, to promote the activity of rubisco enzyme, to enhance the efficiency of photosynthesis, and, finally, to accumulate protein as a percentage of specific dry weight 1.57 times more than that of the control group. Exogenous IAA altered the relative abundance of various amino acids in C. humicola cells, and proteomic analyses showed that exogenous IAA stimulated the algal cells to produce more indole-3-glycerol phosphate (IGP), indole, and serine by up-regulating the enzymes. These precursors are converted to tryptophan under the regulation of tryptophan synthase (A0A383V983), and tryptophan can be metabolized to endogenous IAA to promote the growth of C. humicola. These findings have important implications for the treatment of toxic residual sludge while enriching for high-value amino acids.

The expression of genes encoding novel Sesame oleosin variants facilitates enhanced triacylglycerol accumulation in Arabidopsis leaves and seeds.

Triacylglycerols (TAG), accumulate within lipid droplets (LD), predominantly surrounded by OLEOSINs (OLE), that protect TAG from hydrolysis. We tested the hypothesis that identifying and removing degradation signals from OLE would promote its abundance, preventing TAG degradation and enhancing TAG accumulation. We tested whether mutating potential ubiquitin-conjugation sites in a previously reported improved Sesamum indicum OLE (SiO) variant, o3-3 Cys-OLE (SiCO herein), would stabilize it and increase its lipogenic potential. SiCOv1 was created by replacing all five lysines in SiCO with arginines. Separately, six cysteine residues within SiCO were deleted to create SiCOv2. SiCOv1 and SiCOv2 mutations were combined to create SiCOv3. Transient expression of SiCOv3 in Nicotiana benthamiana increased TAG by two-fold relative to SiCO. Constitutive expression of SiCOv3 or SiCOv5, containing the five predominant TAG-increasing mutations from SiCOv3, in Arabidopsis along with mouse DGAT2 (mD) increased TAG accumulation by 54% in leaves and 13% in seeds compared with control lines coexpressing SiCO and mD. Lipid synthesis rates increased, consistent with an increase in lipid sink strength that sequesters newly synthesized TAG, thereby relieving the constitutive BADC-dependent inhibition of ACCase reported for WT Arabidopsis. These OLE variants represent novel factors for potentially increasing TAG accumulation in a variety of oil crops.

Methyl jasmonate regulation of pectin polysaccharides in Cosmos bipinnatus roots: A mechanistic insight into alleviating cadmium toxicity.

Methyl jasmonate (MeJA), a crucial phytohormone, which plays an important role in resistance to Cadmium (Cd) stress. The cell wall (CW) of root system is the main location of Cd and plays a key role in resistance to Cd toxicity. However, the mechanism effect of MeJA on the CW composition and Cd accumulation remain unclear. In this study, the contribution of MeJA in regulating CW structure, pectin composition and Cd accumulation was investigated in Cosmos bipinnatus. Phenotypic results affirm MeJA's significant role in reducing Cd-induced toxicity in C. bipinnatus. Notably, MeJA exerts a dual impact, reducing Cd uptake in roots while increasing Cd accumulation in the CW, particularly bound to pectin. The molecular structure of pectin, mainly uronic acid (UA), correlates positively with Cd content, consistent in HC1 and cellulose, emphasizing UA as pivotal for Cd binding. Furthermore, MeJA modulates pectin methylesterase (PME) activity under Cd stress, influencing pectin's molecular structure and homogalacturonan (HG) content affecting Cd-binding capacity. Chelate-soluble pectin (CSP) within soluble pectins accumulates a substantial Cd proportion, with MeJA regulating both UA content and the minor component 3-deoxy-oct-2-ulosonic acid (Kdo) in CSP. The study delves into the intricate regulation of pectin monosaccharide composition under Cd stress, revealing insights into the CW's physical defense and Cd binding. In summary, this research provides novel insights into MeJA-specific mechanisms alleviating Cd toxicity in C. bipinnatus, shedding light on complex interactions between MeJA, and Cd accumulation in CW pectin polysaccharide.

Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency.

OBJECTIVE: Melittin and its derivative have been developed to support effective gene delivery systems. Their ability to facilitate endosomal release enhances the delivery of nanoparticle-based gene therapy. Nevertheless, its potential application in the context of viral vectors has not received much attention. Therefore, we would like to optimize the rAAV vector by Melittin analog to improve the transduction efficiency of rAAV in liver cancer cells and explore the mechanism of Melittin analog on rAAV. METHODS: Various melittin-derived peptides were inserted into loop VIII of the capsid protein in recombinant adeno-associated virus vectors. These vectors carrying either gfp or fluc genes were subjected to quantitative polymerase chain reaction assays and transduction assays in human embryonic kidney 293 (HEK293T) cells to investigate the efficiency of vector production and gene delivery. In addition, the ability of a specific p5RHH-rAAV vector to deliver genes was examined through in vitro transduction of different cultured cells and in vivo tail vein administration to C57BL/6 mice. Finally, the intricate details of the vector-mediated transduction mechanisms were explored by using pharmacological inhibitors of every stage of the rAAV2 intracellular life cycle. RESULTS: A total of 76 melittin-related peptides were identified from existing literature. Among them, CMA-3, p5RHH and aAR3 were found to significantly inhibit transduction of rAAV2 vector crude lysate. The p5RHH-rAAV2 vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to rAAV. Mechanistically, bafilomycin A1, a vacuolar endosome acidification inhibitor, completely inhibited the transgene expression mediated by the p5RHH-rAAV2 vectors. Most importantly, p5RHH-rAAV8 vectors also increased hepatic transduction in vivo in C57BL/6 mice. CONCLUSION: The incorporation of melittin analogs into the rAAV capsids results in a significant improvement in rAAV-mediated transgene expression. While further modifications remain an area of interest, our studies have substantially broadened the pharmacological prospects of melittin in the context of viral vector-mediated gene delivery. Please cite this article as: Meng J, He Y, Yang H, Zhou L, Wang S, Feng X, Al-shargi OY, Yu X, Zhu L, Ling, C. Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency. J Integr Med. 2024; 22(1): 72-82.

Quality evaluation of Lonicerae Japonicae Flos from different origins based on high-performance liquid chromatography (HPLC) fingerprinting and multicomponent quantitative analysis combined with chemical pattern recognition.

INTRODUCTION: Lonicerae Japonicae Flos (LJF) is widely used in food and traditional Chinese medicine. To meet demand, Lonicera japonica Thunb. is widely cultivated in many provinces of China. However, reported studies on the quality evaluation of LJF only used a single or a few active components as indicators, which could not fully reflect the quality of LJF. OBJECTIVES: In the present study, we aimed to develop a methodology for comprehensively evaluating the quality of LJF from different origins based on high-performance liquid chromatography (HPLC) fingerprinting and multicomponent quantitative analysis combined with chemical pattern recognition. MATERIALS AND METHODS: The HPLC method was developed for fingerprint analysis and was used to determine the contents of 19 components of LJF. To distinguish between samples and identify differential components, similarity analysis, hierarchical cluster analysis, principal component analysis, and orthogonal partial least squares discriminant analysis were performed. RESULTS: The HPLC fingerprint was established. Using the developed method, the contents of 19 components recognized in the fingerprint analysis were determined. Samples from different origins could be effectively distinguished. CONCLUSIONS: HPLC fingerprinting and multicomponent quantitative analysis combined with chemical pattern recognition is an efficient method for evaluating LJF.

Boron deficiency energizes cyanide uptake and assimilation through activating plasma membrane H+-ATPase in rice plants.

The effect of boron (B) deficiency on mediating the contribution of H+-ATPase in the uptake and assimilation of exogenous cyanide (CN-) is investigated. Under CN- treatments, rice seedlings with B-deficient (-B) conditions exhibited significantly higher CN- uptake and assimilation rates than B-supplemented (+B) seedlings, whereas NH4+ uptake and assimilation rates were slightly higher in -B rice seedlings than in +B. In this connection, the expression pattern of genes encoding ß-CAS, ST, and H+-ATPase was assessed to unravel their role in the current scenario. The abundances of three ß-CAS isogenes (OsCYS-D1, OsCYS-D2, and OsCYS-C1) in rice tissues are upregulated from both "CN--B" and "CN-+B" treatments, however, only OsCYS-C1 in roots from the "CN--B" treatments was significantly upregulated than "CN-+B" treatments. Expression patterns of ST-related genes (OsStr9, OsStr22, and OsStr23) are tissue specific, in which significantly higher upregulation of ST-related genes was observed in shoots from "CN--B" treatments than "CN-+B" treatments. Expression pattern of 7 selected H+-ATPase isogenes, OsA1, OSA2, OsA3, OsA4, OsA7, OsA8, and OsA9 are quite tissue specific between "CN-+B" and "CN--B" treatments. Among these, OsA4 and OsA7 genes were highly activated in the uptake and assimilation of exogenous CN- in -B nutrient solution. These results indicated that B deficiency disturbs the pattern of N cycles in CN--treated rice seedlings, where activation of ST during CN- assimilation decreases the flux of the innate pool of NH4+ produced from CN- assimilation by the ß-CAS pathway in plants. Collectively, the B deficiency increased the uptake and assimilation of exogenous CN- through activating H+-ATPase.

The antinociceptive and anti-alpha-glucosidase effects of glucosides from Hemiphragma heterophyllum Wall.

Hemiphragma heterophyllum Wall. is commonly used in traditional Yi herbal medicine for treating bellyache and toothache. In the current study, an unreported monoterpene glucoside, (S)-thymoquinol O-(6-O-oleuropeoyl)-ß-d-glucopyranoside (1), together with 11 known glucosides were obtained from the whole herb of H. heterophyllum. Their structures were determined based on a detailed analysis of spectroscopic data and acid hydrolysis and methanolysis reactions. Bioassay results showed that compounds 1 and 10 at 40 mg/kg exhibited significant antinociceptive activity in the acetic acid-induced writhing model, with inhibitions of 59.80% and 64.07%, respectively. Moreover, five of the isolates showed moderate anti-α-glucosidase activities with IC50 values ranging from 5.67 to 46.16 µM.

Quality markers of Dajianzhong decoction based on multicomponent qualitative and quantitative analysis combined with network pharmacology and chemometric analysis.

INTRODUCTION: Dajianzhong decoction (DJZD), a classic famous prescription, has a long history of medicinal application. Modern studies have demonstrated its clinical utility in the treatment of postoperative ileus (POI). But none of the current quality evaluation methods for this compound is associated with efficacy. OBJECTIVES: This study aimed to identify the quality markers (Q-Markers) connected to the treatment of POI in DJZD. METHODOLOGY: Ultra-performance liquid chromatography quadrupole Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) was used to identify the main constituents in DJZD. Based on the qualitative results obtained by fingerprinting, chemical pattern recognition (CPR) was used to analyse the key components affecting the quality and finally to establish the network of the active ingredients in DJZD with POI. RESULTS: A total of 64 chemical components were detected. After fingerprint analysis, 13 common peaks were identified. The fingerprint similarity of 15 batches of samples ranged from 0.860 to 1.000. CPR analysis was able to categorically classify 15 batches of DJZD into two groups. And gingerenone A, methyl-6-gingerdiol, 6-gingerol, and hydroxy-ß-sanshool contributed to their grouping. Twelve common components interact with the therapeutic targets for treating POI. In addition, the mechanism of this prescription for treating POI may be related to the jurisdiction of the neurological system, the immunological system, and the inflammatory response. CONCLUSIONS: This integrated approach can accurately assess and forecast the quality of DJZD, presume the Q-Markers of DJZD for POI, and lay the foundation for studying the theoretical underpinnings and exploring the mechanism of DJZD in the treatment of POI.

Ginsenoside Rd Induces Differentiation of Myeloid Leukemia Cells via Regulating ERK/GSK-3ß Signaling Pathway.

OBJECTIVE: To investigate the role of ginsenoside Rd (GRd) in acute myeloid leukemia (AML) cell differentiation. METHODS: AML cells were treated with GRd (25, 50, 100 and 200 µg/mL), retinoic acid (RA, 0.1g/L) and PD98059 (20 mg/mL) for 72 h, cell survival was detected by methylthiazolyldiphenyl-tetrazolium bromide and colony formation assays, and cell cycle was detected by flow cytometry. Cell morphology and differentiation were observed by Wright-Giemsa staining, peroxidase chemical staining and cellular immunochemistry assay, respectively. The protein expression levels of GATA binding protein 1 (GATA-1), purine rich Box-1 (PU.1), phosphorylated-extracellular signal-related kinase (p-ERK), ERK, phosphorylated-glycogen synthase kinase-3ß (p-GSK3ß), GSK3ß and signal transducer and activator of transcription 1 (STAT1) were detected by Western blot. Thirty-six mice were randomly divided into 3 groups using a random number table: model control group (non-treated), GRd group [treated with 200 mg/(kg·d) GRd] and homoharringtonine (HTT) group [treated with 1 mg/(kg·d) HTT]. A tumor-bearing nude mouse model was established, and tumor weight and volume were recorded. Changes of subcutaneous tumor tissue were observed after hematoxylin and eosin staining. WT1 and GATA-1 expressions were detected by immunohistochemical staining. RESULTS: The cell survival was inhibited by GRd in a dose-dependent manner and GRd caused G0/G1 cell arrest (p<0.05). GRd treatment induced leukemia cell differentiation, showing increased expressions of peroxidase and specific proteins concerning erythrogenic or granulocytic differentiation (p<0.05). GRd treatment elicited upregulation of p-ERK, p-GSK-3ß and STAT1 expressions in cells, and reversed the effects of PD98059 on inhibiting the expressions of peroxidase, GATA-1 and PU.1 (P<0.05). After GRd treatment, tumor weight and volume of mice were decreased, and tumor cells underwent massive apoptosis and necrosis (P<0.05). WT1 level was decreased, and GATA-1 level was significantly increased in subcutaneous tumor tissues (P<0.05 or P<0.01). CONCLUSION: GRd might induce the differentiation of AML cells via regulating the ERK/GSK-3ß signaling pathway.

A systematic review and meta-analysis of moxibustion for chronic prostatitis.

BACKGROUND: Chronic prostatitis (CP) is a common condition that affects many individuals. Previous clinical trials have explored the use of moxibustion as a potential treatment for CP. However, the evidence on the effectiveness of moxibustion for CP remains limited. Therefore, this study aimed to comprehensively assess the effects of moxibustion for CP. METHODS: In order to gather relevant and up-to-date information, we conducted a systematic literature search of databases including Cochrane Library, PUBMED, EMBASE, CNKI, and Wangfang from inception until June 30, 2023. Only randomized clinical trials (RCTs) that investigated the use of moxibustion for CP were included in this study. The primary outcomes of interest were the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) scores and the overall response rate. To evaluate the quality of the included studies, we used the Cochrane risk-of-bias tool. RESULTS: After analyzing the data from 8 RCTs involving a total of 664 patients, we found significant differences in NIH-CPSI scores between moxibustion and other treatment modalities. Specifically, when compared with herbal medicine, moxibustion was associated with a mean difference (MD) of -1.78 in NIH-CPSI scores (95% confidence interval [CI] [-2.78, -0.78], P < .001), and when compared with western medicine, moxibustion was associated with a MD of -5.24 in NIH-CPSI scores (95% CI [-7.80, -2.67], P < .08). In terms of the overall response rate, moxibustion was found to be superior to herbal medicine, with a MD of 2.36 (95% [19, 4.67], P = .01). Additionally, when moxibustion was combined with herbal medicine, it yielded a higher overall response rate with a MD of 4.07 (95% CI [1.54, 10.74], P = .005) compared to herbal medicine alone. Moxibustion also outperformed western medicine in terms of the overall response rate, with a MD of 4.56 (95% CI [2.24, 9.26], P < .001). CONCLUSION: Based on the findings of this study, moxibustion appears to be a potentially efficacious treatment for CP. The results suggest that moxibustion can improve NIH-CPSI scores and overall response rate in patients with CP. However, further high-quality studies are needed to validate these results and establish the long-term effects of moxibustion as a treatment for CP.

Amniotic membrane mesenchymal stromal cell-derived secretome in the treatment of acute ischemic stroke: A case report.

BACKGROUND: Stroke is the second and third leading cause of death and disability, respectively. To date, no definitive treatment can repair lost brain function. Recently, various preclinical studies have been reported on mesenchymal stromal cells (MSCs) and their derivatives and their potential as alternative therapies for stroke. CASE SUMMARY: A 45-year-old female suffered an acute stroke, which led to paralysis in the left upper and lower limbs. The amniotic membrane MSC-derived secretome (MSC-secretome) was intravenously transplanted once a week for 4 wk. MSC-secretome-regulated regulatory T cells were investigated for the beneficial effects. The clinical improvement of this patient was accompanied by an increased frequency of regulatory T cells after transplantation. CONCLUSION: Intravenous administration of MSC-secretome can potentially treat patients who suffer from acute ischemic stroke.

[Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHR), and explore preliminarily the mediating role of cholinergic anti-inflammatory pathway (CAP) and its downstream nuclear factor κB (NF-κB) signaling pathway. METHODS: Six 12-week-old WKY male rats were employed as the normal group. Eighteen 12-week-old SHR were randomly divided into 3 groups, i.e. a model group, an EA group and a blocking group (EA after blocking α7 nicotinic acetylcholine receptor [α7nAchR]), with 6 rats in each one. In the EA group, EA was delivered at "Neiguan"(PC 6) and the site 0.5 cm from its left side, with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity. One intervention took 30 min and was given once every 2 days, lasting 8 weeks. In the blocking group, prior to each EA, the α7nAchR specific blocker, α-bungartoxin was injected intravenously in the tails of the rats. After EA intervention, the systolic blood pressure (SBP), the diastolic blood pressure (DBP) and the mean arterial pressure (MAP) were measured with non-invasive blood pressure monitor. Using echocardiogram, the left ventricular (LV) anterior wall end-diastolic thickness (LVAWd) , LV posterior wall end-diastolic thickness (LVPWd) and the LV end-diastolic internal diameter (LVIDd) were measured. The level of hydroxyproline (Hyp) in the myocardial tissue was determined by using alkaline hydrolysis, and that of acetylcholine (Ach) was detected by ELISA. With the real-time PCR adopted, the mRNA expression of NF-κB p65, tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and IL-6 were determined. RESULTS: Compared with the normal group, SBP, DBP, MAP, LVAWd and LVPWd were increased (P<0.01), and LVIDd was decreased (P<0.01) in the rats of the model group. SBP, DBP, MAP and LVAWd were dropped (P<0.01, P<0.05), and LVIDd rose (P<0.01) in the EA group when compared with those in the model group. The differences in the above indexes were not statistically significant between the blocking group and the model group (P>0.05). Compared with the normal group, Hyp level and the mRNA expression of NF-κB p65, TNF-α, IL-1ß and IL-6 in the myocardial tissue increased (P<0.01, P<0.05) and Ach level decreased (P<0.01) in the model group. Hyp level, the mRNA expression of NF-κB p65, TNF-α, IL-1ß and IL-6 in the myocardial tissue were reduced (P<0.05, P<0.01) and Ach level rose (P<0.01) in the EA group when compared with those in the model group. These indexes were not different statistically between the blocking group and the model group (P>0.05). CONCLUSION: CAP may be involved in ameliorating the pathological damage of myocardial fibrosis during EA at "Neiguan"(PC 6). The underlying effect mechanism is associated with up-regulating the neurotransmitter, Ach and down-regulating mRNA expression of NF-κB p65 and pro-inflammatory factors such as TNF-α, IL-1ß and IL-6 in myocardial tissue.

Somatostatin neurons in prefrontal cortex initiate sleep-preparatory behavior and sleep via the preoptic and lateral hypothalamus.

The prefrontal cortex (PFC) enables mammals to respond to situations, including internal states, with appropriate actions. One such internal state could be 'tiredness'. Here, using activity tagging in the mouse PFC, we identified particularly excitable, fast-spiking, somatostatin-expressing, γ-aminobutyric acid (GABA) (PFCSst-GABA) cells that responded to sleep deprivation. These cells projected to the lateral preoptic (LPO) hypothalamus and the lateral hypothalamus (LH). Stimulating PFCSst-GABA terminals in the LPO hypothalamus caused sleep-preparatory behavior (nesting, elevated theta power and elevated temperature), and stimulating PFCSst-GABA terminals in the LH mimicked recovery sleep (non-rapid eye-movement sleep with higher delta power and lower body temperature). PFCSst-GABA terminals had enhanced activity during nesting and sleep, inducing inhibitory postsynaptic currents on diverse cells in the LPO hypothalamus and the LH. The PFC also might feature in deciding sleep location in the absence of excessive fatigue. These findings suggest that the PFC instructs the hypothalamus to ensure that optimal sleep takes place in a suitable place.

Analysis of the mechanism of exogenous indole-3-acetic acid on the enrichment of d-glucose in Chlorococcum humicola cultured by sludge extracts.

Addressing problems of high organic toxicity in the wastewater treatment process, microalgae have been used to reduce the toxicity in sludge and to synthesize non-toxic and recoverable biomass of resources. Phytohormone is a core regulator of plant growth and current research has generally focused on their promotion of cell division and cell expansion. Effects of phytohormone on the enrichment mechanism of microalgae directional polysaccharides accumulation remain poorly elucidated. This study was carried out to investigate the effects of exogenous indole-3-acetic acid (IAA) on growth characteristics, biomass accumulation, and photosynthesis capacity of Chlorococcum humicola cultured in sludge extract and further find the d-glucose enrichment mechanism of it through proteomic. The results indicated that the optimal culture conditions were the 75 % sludge extract and 25 % selenite enrichment (SE) medium with 5 × 10-6 mol/L indole-3-acetic acid. Polysaccharides increased significantly from day 20 and accumulated to (326.59 ± 13.06) mg/L on day 30, in which the d-glucose proportion increased to 61.53 %. Most notably, proteomic tests were performed and found that the photosynthesis-related proteins including the differential proteins of photosystem electron transport, ATP and NADPH catalytic synthesis were significantly up-regulated. At the end of the path, three pathways of d-glucose enrichment with α-d-Glucose-1P as a precursor were summarized through indole-3-acetic acid activation on amylase, endoglucanase and Beta-glucosidase, etc. These results provide insights to explore the directed enrichment of biomass in Chlorococcum humicola by indole-3-acetic acid.

Elucidation of the mechanisms and molecular targets of KeChuanLiuWei-Mixture for treatment of severe asthma based on network pharmacology.

KeChuanLiuWei-Mixture (KCLW) is widely used as a Chinese medicine prescription to treat severe asthma. However, the underlying therapeutic mechanism of KCLW remains unclear. In this study, a network pharmacology method was used to identify the chemical constituents of KCLW by the TCMSP database and ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry. Differential expression identification, protein-protein interaction (PPI) network and functional enrichment analysis were used to screen key targets of KCLW for severe asthma. Our results confirmed that quercetin, luteolin, kaempferol, and wogonin are the most critical active ingredients in KCLW. Moreover, the 16 relevant severe asthma-related targets of KCLW were obtained by overlapping the PPI networks of the KCLW putative targets and severe asthma-related genes, among which the most important targets were IL-6, NOS2, VEGFA, CXCL2, and PLAT. Functionally, the 16-targets and their interacting differentially expressed genes were primarily related to biological functions and pathways related to immunity and inflammation, such as inflammatory response, T cell differentiation, Nrf2/HO-1 signaling pathway, TGF-ß/Smad signaling pathway, and NF-κB signaling pathway. KCLW inhibited inflammation in PDGF-BB-induced airway smooth muscle cells. In summary, this study demonstrates the active substance and potential therapeutic mechanism of KCLW in severe asthma, and offers a clinical direction for KCLW against severe asthma.

Capsaicin improves hypertension and cardiac hypertrophy via SIRT1/NF-κB/MAPKs pathway in the hypothalamic paraventricular nucleus.

BACKGROUND: Hypertension has seriously affected a large part of the adult and elderly population. The complications caused by hypertension are important risk factors for cardiovascular disease accidents. Capsaicin, a pungent component of chili pepper has been revealed to improve hypertension. However, its potential mechanism in improving hypertension remains to be explored. PURPOSE: In the present study, we aimed to investigate whether capsaicin could attenuate the SIRT1/NF-κB/MAPKs pathway in the paraventricular nucleus of hypothalamus (PVN). METHODS: We used spontaneous hypertensive rats (SHRs) as animal model rats. Micro osmotic pump was used to give capsaicin through PVN for 28 days, starting from age12-week-old. RESULTS: The results showed that capsaicin significantly reduced blood pressure from the 16th day of infusion onward. At the end of the experimental period, we measured cardiac hypertrophy index and the heart rate (HR), and the results showed that the cardiac hypertrophy and heart rate of rats was significantly improved upon capsaicin chronic infusion. Norepinephrine (NE) and epinephrine (EPI) in plasma of SHRs treated with capsaicin were also decreased. Additionally, capsaicin increased the protein expression and number of positive cells of SIRT1 and the 67-kDa isoform of glutamate decarboxylase (GAD67), decreased the production of reactive oxygen species (ROS), number of positive cells of NOX2, those of Angiotensin Converting Enzyme (ACE) and p-IKKß, tyrosine hydroxylase (TH), the gene expression levels of NOX4 and pro-inflammatory cytokines. Capsaicin also decreased the relative protein expressions of protein in MAPKs pathway. CONCLUSION: Current data indicated that capsaicin within the PVN improves hypertension and cardiac hypertrophy via SIRT1/NF-κB/MAPKs pathway in the PVN of SHRs, supporting its potential as candidate drug for preventing and improving hypertension.

Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace.

OBJECTIVE: This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder (PTSD). METHODS: The Web of Science database (2007-2022) was searched using the search terms "phytochemicals" and "PTSD," and relevant literature was compiled. Network clustering co-occurrence analysis and qualitative narrative review were conducted. RESULTS: Three hundred and one articles were included in the analysis of published research, which has surged since 2015 with nearly half of all relevant articles coming from North America. The category is dominated by neuroscience and neurology, with two journals, Addictive Behaviors and Drug and Alcohol Dependence, publishing the greatest number of papers on these topics. Most studies focused on psychedelic intervention for PTSD. Three timelines show an "ebb and flow" phenomenon between "substance use/marijuana abuse" and "psychedelic medicine/medicinal cannabis." Other phytochemicals account for a small proportion of the research and focus on topics like neurosteroid turnover, serotonin levels, and brain-derived neurotrophic factor expression. CONCLUSION: Research on phytochemicals and PTSD is unevenly distributed across countries/regions, disciplines, and journals. Since 2015, the research paradigm shifted to constitute the mainstream of psychedelic research thus far, leading to the exploration of botanical active ingredients and molecular mechanisms. Other studies focus on anti-oxidative stress and anti-inflammation. Please cite this article as: Gao B, Qu YC, Cai MY, Zhang YY, Lu HT, Li HX, Tang YX, Shen H. Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace. J Integr Med. 2023; 21(4):385-396.

[Acteoside promotes autophagy and apoptosis of hepatoma cells by regulating JNK signaling pathway].

This study explored the molecular mechanism of acteoside against hepatoma 22(H22) tumor in mice through c-Jun N-terminal kinase(JNK) signaling pathway. H22 cells were subcutaneously inoculated in 50 male BALB/c mice, and then the model mice were classified into model group, low-dose, medium-dose, and high-dose acteoside groups, and cisplatin group. The administration lasted 2 weeks for each group(5 consecutive days/week). The general conditions of mice in each group, such as mental status, diet intake, water intake, activity, and fur were observed. The body weight, tumor volume, tumor weight, and tumor-inhibiting rate were compared before and after administration. Morphological changes of liver cancer tissues were observed based on hematoxylin and eosin(HE) staining, and the expression of phosphorylated(p)-JNK, JNK, B-cell lymphoma-2(Bcl-2), Beclin-1, and light chain 3(LC3) in each tissue was detected by immunohistochemistry and Western blot. qRT-PCR was performed to detect the mRNA expression of JNK, Bcl-2, Beclin-1, and LC3. The general conditions of mice in model and low-dose acteoside groups were poor, while the general conditions of mice in the remaining three groups were improved. The body weight of mice in medium-dose acteoside group, high-dose acteoside group, and cisplatin group was smaller than that in model group(P<0.01). The tumor volume in model group was insignificantly different from that in low-dose acteoside group, and the volume in cisplatin group showed no significant difference from that in high-dose acteoside group. Tumor volume and weight in medium-dose and high-dose acteoside groups and cisplatin group were lower than those in the model group(P<0.001). The tumor-inhibiting rates were 10.72%, 40.32%, 53.79%, and 56.44% in the low-dose, medium-dose, and high-dose acteoside groups and cisplatin group, respectively. HE staining showed gradual decrease in the count of hepatoma cells and increasing sign of cell necrosis in the acteoside and cisplatin groups, and the necrosis was particularly obvious in the high-dose acteoside group and cisplatin group. Immunohistochemical results suggested that the expression of Beclin-1, LC3, p-JNK, and JNK was up-regulated in acteoside and cisplatin groups(P<0.05). The results of immunohistochemistry, Western blot, and qRT-PCR indicated that the expression of Bcl-2 was down-regulated in the medium-dose and high-dose acteoside groups and cisplatin group(P<0.01). Western blot showed that the expression of Beclin-1, LC3, and p-JNK was up-regulated in acteoside and cisplatin groups(P<0.01), and there was no difference in the expression of JNK among groups. qRT-PCR results showed that the levels of Beclin-1 and LC3 mRNA were up-regulated in the acteoside and cisplatin groups(P<0.05), and the level of JNK mRNA was up-regulated in medium-dose and high-dose acteoside groups and cisplatin group(P<0.001). Acteoside promotes apoptosis and autophagy of H22 cells in mice hepatoma cells by up-regulating the JNK signaling pathway, thus inhibiting tumor growth.