Habitual fish oil supplementation and incident chronic obstructive pulmonary disease: Data from a prospective cohort study.

BACKGROUND: Fish oil is one of the most popular supplements in the UK and other developed countries. However, the relationship between fish oil use and chronic obstructive pulmonary disease (COPD) is unclear. OBJECTIVE: To prospectively examine the association of habitual fish oil supplementation with incident COPD risk and to evaluate potential effect modification by genetic predisposition. METHODS: This study included 484,414 participants (mean and standard deviation [SD] age: 56.5 [8.1] years) from the UK Biobank who completed a touchscreen questionnaire on habitual fish oil supplement use between 2006 and 2010 and were followed up through 2018. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for sociodemographic and lifestyle behaviours, health conditions, and other potential confounding factors. A weighted genetic risk score (GRS) for COPD was derived from 112 validated single nucleotide polymorphisms. RESULTS: During a median follow-up of 9.0 years, 8860 incident COPD events were recorded. A total of 31.4% (152,230) of the study participants reported habitual fish oil supplementation at baseline. Habitual fish oil supplementation was significantly associated with a lower risk of incident COPD (adjusted HR: 0.88; 95% CI: 0.84-0.93). The association with COPD did not differ by GRS strata (P for interaction = 0.880). The results from subgroup and sensitivity analyses supported the robustness of our findings. CONCLUSIONS: Our findings suggest that habitual fish oil supplementation is associated with a lower risk of incident COPD, irrespective of genetic predisposition.

Protective Mechanism of Electroacupuncture on Peripheral Neurotoxicity Induced by Oxaliplatin in Rats.

OBJECTIVE: To study the effect of electroacupuncture (EA) on oxaliplatin-induced peripheral neuropathy (OIPN) in rats. METHODS: Male Sprague-Dawley rats were equally divided into 3 groups using a random number table: the control group, the OIPN group, and the EA (OIPN + EA) group, with 10 rats in each. The time courses of mechanical, cold sensitivity, and microcirculation blood flow intensity were determined. The morphology of the dorsal root ganglion (DRG) was observed by electron microscopic examination. The protein levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the transient receptor potential (TRP) protein family in DRGs were assayed by Western blot. RESULTS: EA treatment significantly reduced mechanical allodynia and cold allodynia in OIPN rats (P<0.01). Notably, oxaliplatin treatment resulted in impaired microcirculatory blood flow and pathomorphological defects in DRGs (P<0.01). EA treatment increased the microcirculation blood flow and attenuated the pathological changes induced by oxaliplatin (P<0.01). In addition, the expression levels of Nrf2 and HO-1 were down-regulated, and the TRP protein family was over-expressed in the DRGs of OIPN rats (P<0.01). EA increased the expression levels of Nrf2 and HO-1 and decreased the level of TRP protein family in DRG (P<0.05 or P<0.01). CONCLUSION: EA may be a potential alternative therapy for OIPN, and its mechanism may be mainly mediated by restoring the Nrf2/HO-1 signaling pathway.

Association of Sugar-Sweetened, Artificially Sweetened, and Unsweetened Coffee Consumption With All-Cause and Cause-Specific Mortality : A Large Prospective Cohort Study.

BACKGROUND: Previous observational studies have suggested an association between coffee intake and reduced risk for death, but these studies did not distinguish between coffee consumed with sugar or artificial sweeteners and coffee consumed without. OBJECTIVE: To evaluate the associations of consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee with all-cause and cause-specific mortality. DESIGN: Prospective cohort study. SETTING: Data were extracted from the UK Biobank. PARTICIPANTS: A total of 171 616 participants (mean age, 55.6 years [SD, 7.9]) without cardiovascular disease (CVD) or cancer at baseline were eligible. Baseline demographic, lifestyle, and dietary data from the UK Biobank were used, with follow-up beginning in 2009 and ending in 2018. MEASUREMENTS: Dietary consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee was self-reported. All-cause, cancer-related, and CVD-related mortality were estimated. RESULTS: During a median follow-up of 7.0 years, 3177 deaths were recorded (including 1725 cancer deaths and 628 CVD deaths). Cox models with penalized splines showed U-shaped associations of unsweetened coffee, sugar-sweetened coffee, and artificially sweetened coffee with mortality. Compared with nonconsumers, consumers of various amounts of unsweetened coffee (>0 to 1.5, >1.5 to 2.5, >2.5 to 3.5, >3.5 to 4.5, and >4.5 drinks/d) had lower risks for all-cause mortality after adjustment for lifestyle, sociodemographic, and clinical factors, with respective hazard ratios of 0.79 (95% CI, 0.70 to 0.90), 0.84 (CI, 0.74 to 0.95), 0.71 (CI, 0.62 to 0.82), 0.71 (CI, 0.60 to 0.84), and 0.77 (CI, 0.65 to 0.91); the respective estimates for consumption of sugar-sweetened coffee were 0.91 (CI, 0.78 to 1.07), 0.69 (CI, 0.57 to 0.84), 0.72 (CI, 0.57 to 0.91), 0.79 (CI, 0.60 to 1.06), and 1.05 (CI, 0.82 to 1.36). The association between artificially sweetened coffee and mortality was less consistent. The association of coffee drinking with mortality from cancer and CVD was largely consistent with that with all-cause mortality. U-shaped associations were also observed for instant, ground, and decaffeinated coffee. LIMITATION: Exposure assessed at baseline might not capture changes in intake over time. CONCLUSION: Moderate consumption of unsweetened and sugar-sweetened coffee was associated with lower risk for death. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China, Young Elite Scientist Sponsorship Program by CAST, and Project Supported by Guangdong Basic and Applied Basic Research Foundation.

Age-dependent alteration in metabolism of vitamin B6 , neurotransmitters, and amino acids after 4'-O-methylpyridoxine administration in rats.

4'-O-methylpyridoxine (MPN), a recognized antivitamin B6 compound, is a potentially poisonous substance found in Ginkgo biloba L. In this work, the effects of MPN on the metabolism of vitamin B6 , neurotransmitters, and amino acids were compared in the plasma and brain of young and adult rats under various administration times. Results showed that the contents of MPN residues in the plasma and brain of young rats were 12.72 and 14.76 µM higher than adult rats, respectively. Moreover, the levels of 5-hydroxytryptamine and dopamine in the brain of young rats have decreased by 13.78% and 7.19%, respectively, compared with the control group, at 2 h after MPN administration. Furthermore, the principal component analysis revealed that MPN was an important contributor to the amino acid composition in the brain of young rats. These results suggest that age may lead to different toxic effects of MPN. PRACTICAL APPLICATION: 4'-O-methylpyridoxine is primarily responsible for poisoning due to overconsumption of Ginkgo biloba seeds. This study will provide an exploratory understanding of the age-dependent toxicity of 4'-O-methylpyridoxine.

PLA2 mediates the innate immune response in Asian corn borer, Ostrinia furnacalis.

The eicosanoid signaling pathway mediates insect immune reactions to a wide range of stimuli. This pathway begins with the biosynthesis of arachidonic acid (AA) from the hydrolysis of phospholipids catalyzed by phospholipase A2 (PLA2 ). We report here that the PLA2 inhibitor, dexamethasone (DEX), impaired the innate immune response including nodulation, encapsulation, and melanization in Ostrinia furnacalis larvae, while AA partially reversed these effects of DEX. We cloned a full-length complementary DNA encoding a PLA2 , designated as OfsPLA2 , from O. furnacalis. The open reading frame of OfsPLA2 encodes a 195-amino acid residue protein with a 22-residue signal peptide. Sequence alignment analyses indicated that O. furnacalis PLA2 might be a Group III secretory PLA2 . The highest transcript levels of OfsPLA2 were detected in the fat body, and its transcript levels increased dramatically after infection with Escherichia coli, Micrococcus luteus, or Beauveria bassiana. Recombinant OfsPLA2 significantly induced prophenoloxidase (PPO) activation in larval hemolymph in the presence of Ca2+ and encapsulation of agarose beads. Injection of recombinant OfsPLA2 into larvae resulted in increased transcript levels of attacin, defencin, and moricin-3 genes. Our results demonstrate the involvement of the eicosanoid signaling pathway in the innate immune response of O. furnacalis larvae and provide new information about the roles of O. furnacalis secretory PLA2 in activating PPO and antimicrobial peptide production.

Protective Mechanism of Electroacupuncture on Peripheral Neurotoxicity Induced by Oxaliplatin in Rats / 中国结合医学杂志

OBJECTIVE@#To study the effect of electroacupuncture (EA) on oxaliplatin-induced peripheral neuropathy (OIPN) in rats.@*METHODS@#Male Sprague-Dawley rats were equally divided into 3 groups using a random number table: the control group, the OIPN group, and the EA (OIPN + EA) group, with 10 rats in each. The time courses of mechanical, cold sensitivity, and microcirculation blood flow intensity were determined. The morphology of the dorsal root ganglion (DRG) was observed by electron microscopic examination. The protein levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the transient receptor potential (TRP) protein family in DRGs were assayed by Western blot.@*RESULTS@#EA treatment significantly reduced mechanical allodynia and cold allodynia in OIPN rats (P<0.01). Notably, oxaliplatin treatment resulted in impaired microcirculatory blood flow and pathomorphological defects in DRGs (P<0.01). EA treatment increased the microcirculation blood flow and attenuated the pathological changes induced by oxaliplatin (P<0.01). In addition, the expression levels of Nrf2 and HO-1 were down-regulated, and the TRP protein family was over-expressed in the DRGs of OIPN rats (P<0.01). EA increased the expression levels of Nrf2 and HO-1 and decreased the level of TRP protein family in DRG (P<0.05 or P<0.01).@*CONCLUSION@#EA may be a potential alternative therapy for OIPN, and its mechanism may be mainly mediated by restoring the Nrf2/HO-1 signaling pathway.

Efficacy and safety of acupuncture and moxibustion combined with the external application of traditional Chinese medicine in the treatment of primary liver cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Primary liver cancer (PLC) is one of the most common malignant tumors in the world, and its incidence and fatality rate are increasing year by year. Due to the large population base in China, the aging population is severely affected by environmental pollution, eating habits, and unhealthy lifestyles. And many other influences have caused the number of new PLC cases and deaths in China to rank first in the world. Acupuncture combined with external application of Chinese medicine to treat PLC is currently one of the commonly used treatments in China. However, this combined treatment still lacks evidence-based medicine support. Therefore, this systematic review and meta-analysis aims to evaluate the efficacy and safety of acupuncture combined with external application of traditional Chinese medicine in the treatment of PLC. METHOD: We will search PubMed, Web of Science, GCBI, Embase, OVID, AMED, Cochrane Library, CNKI, VIP, CBM, and Wanfang databases. As of September 15, 2021, there are no restrictions on search language, publication time, and publication status. We will use the following medical keywords to search, including: "acupuncture", "external application of traditional Chinese medicine", and "primary liver cancer". At the same time, we will manually search all reference lists from relevant systematic reviews to find other eligible studies. We will use the random effects model in REVMAN v5.3 for meta-analysis. The study for acupuncture combined with Chinese herbal medicine in the treatment of PLC was a randomized controlled study. Two researchers will independently review the research selection, data extraction, and research quality assessments. Finally, we will observe the outcome measures. RESULTS: This study will provide evidence-based guidance for the treatment of PLC with acupuncture and the external application of traditional Chinese medicine and offers new ideas and methods for the treatment of PLC.

Trilobolide-6-O-isobutyrate suppresses hepatocellular carcinoma tumorigenesis through inhibition of IL-6/STAT3 signaling pathway.

Currently available therapies for hepatocellular carcinoma (HCC), with a high morbidity and high mortality, are only marginally effective and with sharp adverse side effects, which makes it compulsory to explore novel and more effective anticancer molecules. Chinese medicinal herbs exhibited prominent anticancer effects and were applied to supplement clinical cancer treatment. Here, we reported a compound, trilobolide-6-O-isobutyrate (TBB), isolated from the flowers of Wedelia trilobata with a markedly cytotoxic effect on HCC cells. We found that TBB time- and dose-dependently inhibited HCC cells' growth and colony formation in vitro. Moreover, TBB induced cell cycle arrest at the G2/M phase, mitochondrial caspase-dependent apoptosis, and suppressed migration and invasion, as well as the glycolysis of HCC cells. Mechanistically, our data indicated that TBB inhibited the STAT3 pathway activation by directly interacting with the TYR 640/657 sites of the STAT3 protein and decreasing the level of p-STAT3. TBB also regulated the expression of PCNA, Ki67, Cyclin B1, Cyclin E, Bax, Bcl2, MMP2/9, and PGK1 through the inhibition of the IL-6/STAT3 signaling pathway. Lastly, we confirmed that TBB effectively eliminated tumor growth without causing overt toxicity to healthy tissues in the xenograft tumor model. The exploration of anticancer activity and the underlying mechanism of TBB suggested its usage as a promising chemotherapeutic agent for HCC.

Water-Soluble Organic Nanoparticles with Programable Intermolecular Charge Transfer for NIR-II Photothermal Anti-Bacterial Therapy.

Extensive recent efforts have been put on the design of high-performance organic near-infrared (NIR) photothermal agents (PTAs), especially over NIR-II bio-window (1000-1350 nm). So far, the development is mainly limited by the rarity of molecules with good NIR-II response. Here, we report organic nanoparticles of intermolecular charge-transfer complexes (CTCs) with easily programmable optical absorption. By employing different common donor and acceptor molecules to form CTC nanoparticles (CT NPs), absorption peaks of CT NPs can be controllably tuned from the NIR-I to NIR-II region. Notably, CT NPs formed with perylene and TCNQ have a considerably red-shifted absorption peak at 1040 nm and achieves a good photothermal conversion efficiency of 42 % under 1064 nm excitation. These nanoparticles were used for antibacterial application with effective activity towards both Gram-negative and Gram-positive bacteria. This work opens a new avenue into the development of efficient PTAs.

Anti-hemorrhoidal activity of Lian-Zhi-San, a traditional Chinese medicine, in an experimental hemorrhoidal model in rats.

OBJECTIVE: Hemorrhoidal disease (HD) is the most common proctological disease, with an estimated prevalence rate of 4.4%, and a peak in individuals between 45 and 65 years of age. This study was done to evaluate whether Lian-Zhi-San (LZS), a clinically used anti-hemorrhoidal ointment could alleviate the inflammatory injury, with its associated changes of inflammatory cytokines and morphology of anorectal tissues, in an experimental model of HD in rats. METHODS: HD was induced by croton oil preparation (COP) applied to the anorectal region. Rats were then treated with cotton swabs soaked in LZS ointment, water or white vaseline, twice a day for 7 d. At the end of the experiment, HD was evaluated by measuring hemorrhoidal and biochemical parameters along with histopathological observations. RESULTS: In this study, COP induced a significant increase in the macroscopic severity score, anorectal coefficient and Evans blue extravasation, compared to normal rats. Additionally, it greatly enhanced the expression and secretion levels of some important inflammation-related cytokines along with marked histological damage, compared to normal rats. Rats treated with LZS ointment experienced significantly ameliorated Evans blue extravasation (P < 0.05), decreased macroscopic severity score (0.86 ± 0.14 vs. 1.65 ± 0.16) and the anorectal coefficient (P < 0.01); its use also attenuated tissue damage and inhibited the expression and secretion levels of inflammation-related cytokines (interleukin-1ß, interleukin-6 and tumor necrosis factor-α). CONCLUSION: This study validates a preliminary understanding of the use of LZS ointment to treat inflammatory factors and tissue damage in an experimental model of HD in rats.

Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study.

OBJECTIVES: To evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort. METHODS: This population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables. RESULTS: At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080). CONCLUSIONS: Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

Associations of habitual fish oil supplementation with cardiovascular outcomes and all cause mortality: evidence from a large population based cohort study.

OBJECTIVES: To evaluate the associations of habitual fish oil supplementation with cardiovascular disease (CVD) and mortality in a large prospective cohort. DESIGN: Population based, prospective cohort study. SETTING: UK Biobank. PARTICIPANTS: A total of 427 678 men and women aged between 40 and 69 who had no CVD or cancer at baseline were enrolled between 2006 and 2010 and followed up to the end of 2018. MAIN EXPOSURE: All participants answered questions on the habitual use of supplements, including fish oil. MAIN OUTCOME MEASURES: All cause mortality, CVD mortality, and CVD events. RESULTS: At baseline, 133 438 (31.2%) of the 427 678 participants reported habitual use of fish oil supplements. The multivariable adjusted hazard ratios for habitual users of fish oil versus non-users were 0.87 (95% confidence interval 0.83 to 0.90) for all cause mortality, 0.84 (0.78 to 0.91) for CVD mortality, and 0.93 (0.90 to 0.96) for incident CVD events. For CVD events, the association seemed to be stronger among those with prevalent hypertension (P for interaction=0.005). CONCLUSIONS: Habitual use of fish oil seems to be associated with a lower risk of all cause and CVD mortality and to provide a marginal benefit against CVD events among the general population.

Acupotomy for knee osteoarthritis: A systematic review protocol.

BACKGROUND: Knee osteoarthritis (KOA) is the most common form of arthritis, leading to pain disability in seniors and increased health care utilization. Acupotomy has been widely used to treat KOA. But its efficiency has not been scientifically and methodically evaluated. The aim of this study is to evaluate the efficacy and safety of acupotomy for the treatment of patients with KOA. METHODS: Relevant studies will be searched from the databases of PubMed, EMBASE, Cochrane Library, China Knowledge Resource Integrated Database, Weipu Database for Chinese Technical Periodicals, SinoMed, and Wanfang Database from their inception to June 10, 2019. Two researchers will independently select studies, collect data, and assess the methodology quality by the Cochrane risk of bias tool. RESULTS: The systematic review will provide high-quality evidence to assess the efficacy and safety of acupotomy for KOA by pain, stiffness, and dysfunction of knee joint, and quality of life, as well as adverse events. CONCLUSION: The systematic review will provide evidence to assess the effectiveness and safety of acupotomy therapy for KOA patients. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019132082.

Transcriptional profiling of uterine leiomyoma rats treated by a traditional herb pair, Curcumae rhizoma and Sparganii rhizoma.

The aim of this study was to elucidate the concise effects of a traditional herb pair, Curcumae rhizoma-Sparganii rhizoma (CRSR), on uterine leiomyoma (UL) by analyzing transcriptional profiling. The UL rat model was made by intramuscular injection of progesterone and gavage administration of diethylstilbestrol. From 11 weeks of the establishment of the model, rats of the UL+CRSR group were gavaged daily with CRSR (6.67 g/kg). The serum concentrations of progesterone (P) and estradiol (E2) were determined by radioimmunoassay, the uterine index was measured by caliper measurement, and the pathological status was observed by hematoxylin and eosin stain. Gene expression profiling was checked by NimbleGen Rat Gene Expression Microarrays. The results indicated that the uterine mass of UL+CRSR rats was significantly shrunk and serum P and E2 levels significantly reduced compared to UL animals and nearly to the level of normal rats. Results of microarrays displayed the extensive inhibition of CRSR upon the expression of proliferation and deposition of extracellular matrix (ECM)-related genes, and significantly regulated a wide range of metabolism disorders. Furthermore, CRSR extensively regulated key pathways of the UL process, such as MAPK, PPAR, Notch, and TGF-ß/Smad. Regulation of the crucial pathways for the UL process and ECM metabolism may be the underlying mechanisms of CRSR treatment. Further studies will provide clear clues for effectively treating UL with CRSR.

Dual Fenton Catalytic Nanoreactor for Integrative Type-I and Type-II Photodynamic Therapy Against Hypoxic Cancer Cells.

Tumor hypoxia is a noteworthy impediment to effective photodynamic therapy (PDT), as it would sharply weaken the effectiveness of oxygen-dependent PDT. To enable effective PDT in both hypoxia as well as normoxia circumstances, here, we report a multifunctional nanoreactor (C3N4/MnO2 NPs), which guarantees effective type-II PDT (oxygen-dependent) in hypoxia by in situ oxygen generation via the Fenton reaction. In addition, the C3N4/MnO2 NPs can also be used for oxygen-independent type-I PDT by evolving the cytotoxic hydroxyl radical to reduce reliance on intracellular oxygen content. In vitro cytotoxicity assays made evident that the C3N4/MnO2 NPs exhibit a much higher cancer-cell-killing ability than C3N4 NPs not only in normoxia but also in hypoxic circumstances. The smart integration of type-I and type-II PDT into the therapeutic nanoplatform enables effective PDT even though intracellular oxygen is not satisfactory.

Transcriptional profiling of uterine leiomyoma rats treated by a traditional herb pair, Curcumae rhizoma and Sparganii rhizoma

The aim of this study was to elucidate the concise effects of a traditional herb pair, Curcumae rhizoma-Sparganii rhizoma (CRSR), on uterine leiomyoma (UL) by analyzing transcriptional profiling. The UL rat model was made by intramuscular injection of progesterone and gavage administration of diethylstilbestrol. From 11 weeks of the establishment of the model, rats of the UL+CRSR group were gavaged daily with CRSR (6.67 g/kg). The serum concentrations of progesterone (P) and estradiol (E2) were determined by radioimmunoassay, the uterine index was measured by caliper measurement, and the pathological status was observed by hematoxylin and eosin stain. Gene expression profiling was checked by NimbleGen Rat Gene Expression Microarrays. The results indicated that the uterine mass of UL+CRSR rats was significantly shrunk and serum P and E2 levels significantly reduced compared to UL animals and nearly to the level of normal rats. Results of microarrays displayed the extensive inhibition of CRSR upon the expression of proliferation and deposition of extracellular matrix (ECM)-related genes, and significantly regulated a wide range of metabolism disorders. Furthermore, CRSR extensively regulated key pathways of the UL process, such as MAPK, PPAR, Notch, and TGF-β/Smad. Regulation of the crucial pathways for the UL process and ECM metabolism may be the underlying mechanisms of CRSR treatment. Further studies will provide clear clues for effectively treating UL with CRSR.

The Dysfunction of the Cerebellum and Its Cerebellum-Reward-Sensorimotor Loops in Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is a common itchy skin disease. Despite its prevalence, the neuropathology of CSU is uncertain. In this study, we explored resting state functional connectivity (rs-FC) changes in CSU, as well as how the symptom changes following intervention can modulate rs-FC. Forty patients and 40 healthy controls (HCs) were recruited. Following an intervention, 32 patients participated in a second scan approximately 6 weeks after the first scan. Compared with healthy controls, CSU subjects exhibited higher regional homogeneity (ReHo) values in the cerebellum, which were positively associated with urticaria activity scores over 7 days (UAS7) at baseline. After an intervention accompanied with clinical improvement, we found that ReHo values decreased at the cerebellum and increased at the bilateral primary somatosensory cortex (SI)/primary motor cortex (MI)/supplementary motor area (SMA). Using the cerebellum as a seed, CSU subjects exhibited increased rs-FC with reward regions when compared with HCs and exhibited decreased rs-FC at the right orbitofrontal cortex and right sensorimotor region following the intervention. The improvement rate values were positively associated with reduced rs-FC values in the two regions. Using the cluster of SI/MI/SMA as a seed, CSU patients exhibited decreased rs-FC with the left putamen, caudate, accumbens, and thalamus following the intervention. These results demonstrate the altered cerebellar activity and cerebellum-reward-sensorimotor loops in CSU.

Mitochondria-Associated Apoptosis in Human Melanoma Cells Induced by Cardanol Monoene from Cashew Nut Shell Liquid.

Cardanol monoene (CM) is the major phenolic component extracted from cashew nut shell liquid (CNSL), which has been relevant to wide range of biological effects. In this study, we found that CM could inhibit the M14 human melanoma cells proliferation in a dose dependent and time dependent manner, and the IC50 values were determined to be 23.15 ± 2.42 µM and 12.30 ± 1.67 µM after 24 and 48 h treatment, respectively. The flow cytometric analysis demonstrated that CM induced M14 cell cycle arrest at the S phase, along with the collapse of mitochondrial membrane potential (ΔΨm) and the accumulation of reactive oxygen species (ROS) level in cells, but the apoptotic cells reduced when treated with Z-VAD-FMK (pan-caspase inhibitor). Western blotting showed that the expressions of p53, cytosol cytochrome C, cleaved-caspase-3, and cleaved-PARP were up-regulated, and the expression level of Bax/Bcl-2 ratio increased significantly. The 2527 significant differentially expressed genes were obtained by RNA-seq, which were assigned to 270 KEGG pathways. These results indicated that CM induced M14 cells apoptosis via the ROS triggered mitochondrial-associated pathways, which supports the potential application of CM for the therapy of melanoma cancer.

EVALUATION OF EFFECTIVENESS IN A NOVEL WOUND HEALING OINTMENT-CROCODILE OIL BURN OINTMENT.

BACKGROUND: Crocodile oil and its products are used as ointments for burns and scalds in traditional medicines. A new ointment formulation - crocodile oil burn ointment (COBO) was developed to provide more efficient wound healing activity. The purpose of the study was to evaluate the burn healing efficacy of this new formulation by employing deep second-degree burns in a Wistar rat model. The analgesic and anti-inflammatory activities of COBO were also studied to provide some evidences for its further use. MATERIALS AND METHODS: The wound healing potential of this formulation was evaluated by employing a deep second-degree burn rat model and the efficiency was comparatively assessed against a reference ointment - (1% wt/wt) silver sulfadiazine (SSD). After 28 days, the animals were euthanized and the wounds were removed for transversal and longitudinal histological studies. Acetic acid-induced writhing in mice was used to evaluate the analgesic activity and its anti-inflammatory activity was observed in xylene -induced edema in mice. RESULTS: COBO enhanced the burn wound healing (20.5±1.3 d) as indicated by significant decrease in wound closure time compared with the burn control (25.0±2.16 d) (P<0.01). Hair follicles played an importance role in the physiological functions of the skin, and their growth in the wound could be revealed for the skin regeneration situation. Histological results showed that the hair follicles were well-distributed in the post-burn skin of COBO treatment group, and the amounts of total, active, primary and secondary hair follicles in post-burn 28-day skin of COBO treatment groups were more than those in burn control and SSD groups. On the other hand, the analgesic and anti-inflammatory activity of COBO were much better than those of control group, while they were very close to those of moist exposed burn ointment (MEBO). CONCLUSIONS: COBO accelerated wound closure, reduced inflammation, and had analgesic effects compared with SSD in deep second degree rat burn model. These findings suggest that COBO would be a potential therapy for treating human burns. Abbreviations: COBO, crocodile oil burn ointment; SSD, silver sulfadiazine; MEBO, moist exposed burn ointment; TCM, traditional Chinese medicine; CHM, Chinese herbal medicine; GC-MS, gas chromatography-mass spectrometry.

Free and Easy Wanderer Plus (FEWP) improves behavioral deficits in an animal model of post-traumatic stress disorder by stimulating allopregnanolone biosynthesis.

Post-traumatic stress disorder (PTSD) is a severe psychiatric condition defined as a "trauma and stress-related disorder". Dampened allopregnanolone biosynthesis has been implicated as a possible contributor to PTSD aetiology. Free and Easy Wanderer Plus (FEWP) is a traditional Chinese medicine previously shown to be effective in PTSD treatment. However, little is known about the role of allopregnanolone in the anti-PTSD effects of FEWP. To evaluate this, the single prolonged stress (SPS) model was used in the present study. SPS-induced rats were administered FEWP (at doses of 2.5, 5.0 and 10.0 mg/kg, p.o.) after induction of SPS from days 2 through 15. After exposure to SPS, behavioral assessments were determined, including the open-field test, the contextual fear paradigm, and the elevated plus-maze test. The experimental model rats were decapitated at the end of the behavioral tests and the level of allopregnanolone in the prefrontal cortex, hippocampus and amygdala was measured by enzyme linked immunosorbent assay (ELISA). The behavioral deficits of the SPS-induced rats were significantly reversed by FEWP (at doses of 5.0 and 10.0 mg/kg, p.o.). The level of allopregnanolone was increased by administration of FEWP. In summary, this study indicated that the anti-PTSD effects of FEWP were associated with allopregnanolone biosynthesis.