Tetrahydropalmatine promotes random skin flap survival in rats via the PI3K/AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Flap necrosis is the most common complication after flap transplantation, but its prevention remains challenging. Tetrahydropalmatine (THP) is the main bioactive component of the traditional Chinese medicine Corydalis yanhusuo, with effects that include the activation of blood circulation, the promotion of qi, and pain relief. Although THP is widely used to treat various pain conditions, its impact on flap survival is unknown. AIM OF THE STUDY: To explore the effect and mechanism of THP on skin flap survival. MATERIALS AND METHODS: In this study, we established a modified McFarlane flap model, and the flap survival rate was calculated after 7 days of THP treatment. Angiogenesis and blood perfusion were evaluated using lead oxide/gelatin angiography and laser Doppler, respectively. Flap tissue obtained from zone II was evaluated histopathologically, by hematoxylin and eosin staining, and in assays for malondialdehyde content and superoxide dismutase activity. Immunofluorescence was performed to detect interleukin (IL)-6, tumor necrosis factor (TNF)-α, hypoxia-inducible factor (HIF)-1α, Bcl-2, Bax, caspase-3, caspase-9, SQSTM1/P62, Beclin-1, and LC3 expression, and Western blot to assess PI3K/AKT signaling pathway activation and Vascular endothelial growth factor (VEGF) expression. The role played by the autophagy pathway in flap necrosis was examined using rapamycin, a specific inhibitor of mTOR. RESULTS: Experimentally, THP improved the survival rate of skin flaps, promoted angiogenesis, and improved blood perfusion. THP administration reduced the inflammatory response, oxidative stress, and apoptosis in addition to inhibiting autophagy via the PI3K/AKT/mTOR pathway. Rapamycin partially reversed these effects. CONCLUSION: THP promotes skin flap survival via the PI3K/AKT signaling pathway.

Integrating network pharmacology and experimental verification to investigate the pharmacological mechanisms of Buzhong Yiqi decoction in the treatment of non-small cell lung cancer.

Among all types of cancers, non-small cell lung cancer (NSCLC) exhibits the highest mortality rate with a five-year survival rate below 17% for patients. The Buzhong Yiqi decoction (BZYQD), traditional Chinese medicine (TCM) formula, has been reported to exhibit clinical efficacy in the treatment of NSCLC. Nevertheless, the underlying molecular mechanism remains elusive. This study aimed to assess the mechanistic actions exerted by BZYQD against NSCLC using network pharmacological analysis and experimental validation. The public databases were searched for active compounds in BZYQD, their potential targets, and NSCLC-related targets. The protein-protein interaction (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the core targets and signaling pathways of BZYQD against NSCLC. After screening, this study validated the results of predictions through in vitro experiments and public databases. We found 192 common targets between BZYQD and NSCLC. KEGG analysis showed that the anti-NSCLC effects of BZYQD were mediated through the PI3K-AKT signaling pathway. The results of in vitro experiment indicated that BZYQD could inhibit cell viability and proliferation of A549 and H1299 cells apart from inducing cell apoptosis. In addition, western blot results substantiated that BZYQD could treat NSCLC by inhibiting the activation of the PI3K-AKT signaling pathway. The current study investigated the pharmacological mechanism of BZYQD against NSCLC via network pharmacology and in vitro analyses. Overall, the results revealed that BZYQD could be a promising therapeutic agent for the treatment of NSCLC in the future. Still, more experimental investigations are needed to confirm the applicability of BZYQD for clinical trials.

L-Borneol promotes skin flap survival by regulating HIF-1α/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The clinical application of skin flaps in surgical reconstruction is frequently impeded by the occurrence of distant necrosis. L-Borneol exhibits myogenic properties in traditional Chinese medicine and is used in clinical settings to promote wound healing and conditions such as stroke. Nevertheless, the precise mechanism by which borneol exerts its protective effects on skin flap survival remains unclear. AIM OF THE STUDY: To explore the potential of L-borneol to promote skin flap survival and elucidate the underlying mechanisms. MATERIALS AND METHODS: Thirty-six male Sprague-Dawley rats were randomly divided into three groups: a high-dose (200 mg/kg L-borneol per day), a low-dose (50 mg/kg/day), and control group (same volume of solvent). In each rat, a modified rectangular McFarlane flap model measuring 3 × 9 cm was constructed. Daily intragastric administration of L-borneol or solvent was performed. The flap was divided into three square sections of equal size, namely Zone I (the proximal zone), Zone II (the intermediate zone), and Zone III (the distal zone). The survival rate was quantified, and the histological state of each flap was evaluated on the seventh day following the surgical procedure. The assessment of angiogenesis was conducted using lead oxide/gelatin angiography, whereas the evaluation of blood flow in the free flap was performed using laser Doppler flow imaging. Superoxide dismutase activity was detected using the water-soluble tetrazolium salt-8 method. The quantities of vascular endothelial growth factor, interleukin (IL)-1ß, IL-6, and tumour necrosis factor-α were determined using immunohistochemistry. The levels of nuclear transcription factor-κB, hypoxia-inducible factor-1, B-cell lymphoma-2 (BCL-2), and BCL-2-associated X (BAX) were determined by Western blotting technique. RESULTS: Flap survival rate significantly improved and neutrophil recruitment and release were enhanced after treatment with the compound. Angiogenesis was promoted. L-borneol protected against oxidative stress by increasing superoxide dismutase activity and decreasing malondialdehyde content. It downregulated the hypoxia-inducible factor nuclear transcription factor-κB pathway, leading to the inhibition of several inflammatory factors. Simultaneously, it facilitated the expression of vascular endothelial growth factor and BCL-2. CONCLUSION: The study shows that L-borneol may promote skin flap survival by inhibiting HIF-1α/NF-κB pathway.

Clinical Effects of Exercise Combined with Respiratory Training in the Rehabilitation Treatment of Patients with Chronic Obstructive Pulmonary Disease.

Objective: This study aimed to evaluate the impact of exercise and respiratory training for chronic obstructive pulmonary disease (COPD) patients on specific COPD-related outcomes, such as lung function, exercise capacity, and patient prognosis. Methods: This work had a retrospective design. The subjects of this study were 90 patients with COPD who were treated in our hospital from May 2020 to May 2021. The patients were divided into two groups according to whether they performed exercise combined with respiratory training based on conventional treatment. After two weeks of intervention, the difference in rehabilitation outcomes between the two groups was detected at the first and third months after discharge. Results: The rehabilitation compliance of the observation group was significantly higher than that of the control group (95.56% vs. 77.78%, P < .05). The forced expiratory volume in one second (FEV1) (2.66±0.71 vs. 2.28±0.48, P = .004), forced vital capacity (FVC) (3.30±0.70 vs. 3.00±0.63, P = .035), FEV1/FVC (80.61±8.01% vs. 76.77±7.34%, P = .020), maximal ventilation volume per minute (MVV) (96.14±3.50 vs. 91.20±4.97, P < .001), partial pressure of blood oxygen (PaO2) (89.52±6.87 vs. 82.65±6.54, P < .001), and oxygen saturation of blood (SaO2) (98.05±1.27 vs. 95.90±1.42, P < .001) in the observation group were significantly higher than those in the control group. In contrast, arterial partial pressure of carbon dioxide (PaCO2) (39.52±1.66 vs. 43.21±2.01, P < .001) was significantly lower than that in the control group. The observation group's 6-minute walking distance (6MWD) (401.05±65.66 vs. 360.25±54.94, P = .002) after treatment was significantly longer than those of the control group. The acute exacerbation rate (6.67% vs. 20.00%, P = .036), rehospitalization rate (4.44% vs. 17.78%, P = .044), and mortality rate (0.00% vs. 8.89%, P = .041) of the observation group were lower than those of the control group. Conclusion: The application of exercise training combined with respiratory training in the rehabilitation treatment of COPD patients can more effectively promote the improvement of lung function, blood gas indexes, exercise endurance, and respiratory function and can improve the symptoms of dyspnea, with a good prognosis. This study confirmed the additional health benefits of exercise/respiratory training for COPD patients and provides evidence for the application of exercise/respiratory training in clinical practice. Therefore, it is recommended that in clinical practice, the necessity of exercise/respiratory training in COPD patients needs to be considered. However, the duration of intervention and follow-up period in this study were short, and longer intervention and follow-up are still needed to further confirm the results of this study.

Abamectin induced brain and liver toxicity in carp: The healing potential of silybin and potential molecular mechanisms.

Abamectin (ABM) abuse contaminated aquatic environment and posed a potential threat to fish health as well as public safety. Silybin (SIL), a flavonoid, has been widely used as a novel feed additive to promote fish health. This research was to explore the potential antagonistic mechanism between ABM and SIL on brain and liver toxicity was investigated in common carp. Sixty carp were divided into four groups at random: the Control group, the SIL group, the ABM group, and ABM + SIL group. This experiment lasted for 30 d. According to behavioral observation, the detection of levels of acetylcholinesterase (AchE), iron, and mRNA expression levels of blood-brain barrier (BBB) related tight junction proteins (ZO-1, Claudin7, Occludin, MMP2, MMP9, and MMP13) in brain tissues, it was found that SIL relieved neurobehavioral disorders caused by ABM-induced BBB destruction in carp. H&E staining showed SIL mitigated nerve injury and liver injury caused by ABM. Oil Red O staining and liver-related parameters showed that SIL alleviated hepatotoxicity and lipid metabolism disorder caused by ABM exposure. Furthermore, this work also explored the specific molecular mechanism of SIL in liver protection and neuroprotection. It was shown that SIL lowered ROS levels in liver and brain tissues via the GSK-3ß/TSC2/TOR pathway. Simultaneously, SIL inhibited NF-κB signaling pathway and played an anti-inflammatory role. In conclusion, we believed that SIL supplementation has a protective effect on the brain and liver by regulating oxidative stress and inflammation.

Efficacy and safety of the compound Chinese herb medicine mouthwash on oral ulcer model in rats.

The present study aimed to evaluate the effect of a mouthwash containing a novel compound Chinese herbal medicine (artemisia capillaris, chrysanthemum, honeysuckle, angelica dahurica and asarum sieboldii) on oral ulcers and analyze sub chronic oral toxicity in rats. For efficacy study, mouthwash was administered on the ulcer area twice daily. Compared with the control group, healing time in the test group was shorter and the ulcer area was smaller. Histological analysis showed less inflammatory cell infiltration in the test group. For sub chronic oral toxicity, mouthwash was administered by oral gavage for 93 consecutive days. There were no significant differences in body weight, food consumption or organ coefficients between the test and control groups. Some parameters of haematology and serum chemistry were statistically different but within normal physiological ranges. No obvious abnormalities were found in the necropsies and histopathological observations. In conclusion, the compound Chinese herbal medicine mouthwash promoted oral ulcer healing in rats with no obvious sub chronic toxicity, providing a potential alternative therapeutic strategy for oral ulcers.

Ameliorative effects of silybin against avermectin-triggered carp spleen mitochondrial dysfunction and apoptosis through inhibition of PERK-ATF4-CHOP signaling pathway.

The aim of this study was to investigate the splenic tissue damage of environmental biological drug avermectin to freshwater cultured carp and to evaluate the effect of silybin on the splenic tissue damage of carp induced by avermectin. A total of 60 carp were divided into 4 groups with 15 carp in each group, including the control group fed with basic diet, experimental group fed with basal diet and exposed to avermectin (avermectin group), experimental group fed with basal diet supplement silybin (silybin group), and experimental group fed with basal diet supplement silybin and exposed to avermectin (silybin + avermectin group). The whole test period lasted for 30 days, and spleen tissue was collected for analysis. In this study, H&E staining, mitochondrial purification and membrane potential detection, ATP detection, DHE staining, biochemical tests, qPCR, immunohistochemistry, and apoptosis staining were used to evaluate the biological processes of spleen tissue injury, mitochondrial function, oxidative stress, apoptosis, and endoplasmic reticulum stress. The results show that silybin protected carp splenic tissue damage caused by chronic avermectin exposure, decreased mitochondrial membrane potential, decreased ATP content, ROS accumulation, oxidative stress, apoptosis, and endoplasmic reticulum stress. Silybin may ameliorate the splenic tissue damage of cultured freshwater carp caused by environmental biopesticide avermectin by alleviating mitochondrial dysfunction and inhibiting PERK-ATF4-CHOP-driven mitochondrial apoptosis. Adding silybin into the diet becomes a feasible strategy to resist the pollution of avermectin and provides a theoretical basis for creating a good living environment for freshwater carp.

Development and validation of an LC-MS/MS method for detection of glycyrol in rat plasma and its application to a pharmacokinetic study.

Licorice (Glycyrrhiza uralensis) is one of the most popular edible and medicinal plants and is widely used in Asia. Glycyrol (GC) is a major coumarin present in licorice that exhibits various biological activities. We aimed to develop a highly sensitive and rapid liquid chromatography coupled with mass spectrometry method for the quantitative determination analysis of GC in rat plasma. GC showed linear calibration ranges of 1-100 and 50-2,000 ng/ml with correlation coefficients >0.99. The average extraction recovery ranged from 113.26 to 114.84%, and the relative standard deviation of internal standard normalized matrix factors ranged from 6.36 to 9.46%. The intra-day and inter-day precisions of GC were <15%, and the accuracy ranged from 95.31 to 112.72%. Pharmacokinetic studies showed that GC was distributed in the body with a volume of distribution of 9.06 L/kg, and the initial plasma concentration was 3275.11 ng/ml. The area under the plasma concentration vs. time curve was 479.25 ng h/ml. It was rapidly eliminated with a terminal elimination half-life of 1.47 h and a clearance rate of 4.24 L/h/kg. The pharmacokinetic results can help us to better understand the pharmacological effects of GC in the body.

Essential oil from the roots of Paeonia lactiflora pall. has protective effect against corticosterone-induced depression in mice via modulation of PI3K/Akt signaling pathway.

For thousands of years, the roots of Paeonia lactiflora Pall (PLP) has been considered by traditional Chinese medicine as a drug that can improve mental or emotional disorders, including depression, anxiety and affective disorders. Unfortunately, the research on the mechanism of action and active ingredients of this beneficial drug is not comprehensive. This study focused on the activity of essential oil from PLP (EOP), systematically studied the antidepressant effect of EOP for the first time, and discussed the potential mechanism of its antidepressant effect. In this study, we used a mouse model of corticosterone (CORT)-induced depression, and found that EOP had a significant antidepressant effect on the symptoms of CORT-induced depression in mice, and significantly down-regulated the levels of CRH, ACTH and cortisol in the brain tissues of mice. In addition, we found that EOP treatment alleviated CORT-induced hippocampal neuron injury in mice In vitro experiments. It was also found that EOP could inhibit CORT-induced apoptosis and improve the proliferation ability and cell viability of PC12 cells. Further, with the help of network analysis, it was revealed that PI3K-Akt might be one of the main signaling pathways of EOP against CORT-induced hippocampal neuron apoptosis. In this study, we also found that EOP up-regulated the phosphorylation of PI3K and Akt in CORT-induced mouse hippocampal neurons and PC12 cells, and promoted the nuclear transcription of Nrf2 in CORT-induced PC12 cells. In conclusion, with the integrated approach, we demonstrated that EOP exerted anti-apoptotic effects on hippocampal neurons through PI3K/Akt/Nrf2 signaling pathway.

An Initial Study on Multi-Point Laser Acupuncture Based on 2-D Galvo Mirror.

Currently, the majority of commercially available laser acupuncture instruments are still hand-held and only support single-point stimulation. Simultaneous multi-point stimulation improves the therapeutic efficacy of laser acupuncture by stimulating multiple acupoints at the same time. A "2-dimensional (2-D) galvo mirror" was utilized as a positioning laser acupuncture device for multi-acupoints stimulation. Due to its ability to perform 2-D fast scanning, a single laser beam was reflected by the mirror and stimulated multiple acupuncture points simultaneously. This introduction to the new system, presents its architecture, and shows some initial results. This initial stage of development was focused on the acupoints of the human forearm. This proposed system is the first low-cost, noncontact laser acupuncture system that enables continuous multi-acupoint stimulation with a single laser beam. Notably, it is technically feasible to develop this technique into a whole-body laser acupuncture stimulation system.

Non-target toxic effects of avermectin on carp spleen involve oxidative stress, inflammation, and apoptosis.

Avermectin is one of the most widely used pesticides, but its toxicity to non-target organisms, especially aquatic organisms, has been ignored. Therefore, an acute spleen injury model of avermectin in carp was established to assess the non-target toxicity of avermectin to carp. In this study, 3.005 µg/L and 12.02 µg/L were set as the low and high dose groups of avermectin, respectively, and a four days acute exposure experiment was conducted. Pathological structure observation showed that avermectin damaged spleen tissue structure and produced inflammatory cell infiltration. Biochemical analysis showed that avermectin significantly reduced the activities of antioxidant enzymes CAT, SOD, and GSH-px, but increased the content of MDA, a marker of oxidative damage. Avermectin exposure also significantly increased the transcription levels of inflammatory cytokines such as IL-1ß, IL-6, TNF-α, and INOS, and also significantly enhanced the activity of the inflammatory mediator iNOS, but suppressed the transcription levels of anti-inflammatory factors TGF-ß1 and IL-10. In addition, TUNEL detected that the apoptosis rate increased significantly with the increase of avermectin dosage, and the transcription levels of apoptosis-related genes BAX, P53, and Caspase 3/9 also increased in a dose-dependent manner. This study is preliminary evidence that avermectin induces spleen injury in carp through oxidative stress, inflammation, and apoptosis, which has important implications for subsequent studies on the effects of avermectin on non-target organisms.

Herb-Drug Interaction Between Xiyanping Injection and Lopinavir/Ritonavir, Two Agents Used in COVID-19 Pharmacotherapy.

The global epidemic outbreak of the coronavirus disease 2019 (COVID-19), which exhibits high infectivity, resulted in thousands of deaths due to the lack of specific drugs. Certain traditional Chinese medicines (TCMs), such as Xiyanping injection (XYPI), have exhibited remarkable benefits against COVID-19. Although TCM combined with Western medicine is considered an effective approach for the treatment of COVID-19, the combination may result in potential herb-drug interactions in the clinical setting. The present study aims to verify the effect of XYPI on the oral pharmacokinetics of lopinavir (LPV)/ritonavir (RTV) using an in vivo rat model and in vitro incubation model of human liver microsomes. After being pretreated with an intravenous dose of XYPI (52.5 mg/kg) for one day and for seven consecutive days, the rats received an oral dose of LPV/RTV (42:10.5 mg/kg). Except for the t1/2 of LPV is significantly prolonged from 4.66 to 7.18 h (p < 0.05) after seven consecutive days pretreatment, the pretreatment resulted in only a slight change in the other pharmacokinetic parameters of LPV. However, the pharmacokinetic parameters of RTV were significantly changed after pretreatment with XYPI, particularly in treatment for seven consecutive days, the AUC0-∞ of RTV was significantly shifted from 0.69 to 2.72 h µg/mL (p < 0.05) and the CL exhibited a tendency to decrease from 2.71 L/h to 0.94 L/h (p < 0.05), and the t1/2 of RTV prolonged from 3.70 to 5.51 h (p < 0.05), in comparison with the corresponding parameters in untreated rats. After administration of XYPI, the expression of Cyp3a1 protein was no significant changed in rats. The in vitro incubation study showed XYPI noncompetitively inhibited human CYP3A4 with an apparent Ki value of 0.54 mg/ml in a time-dependent manner. Our study demonstrated that XYPI affects the pharmacokinetics of LPV/RTV by inhibiting CYP3A4 activity. On the basis of this data, patients and clinicians can take precautions to avoid potential drug-interaction risks in COVID-19 treatment.

Sub-chronic exposure to realgar induces liver injury via upregulating the TXNIP/NLRP3 pathway and disturbing bile acid homeostasis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar is a traditional Chinese medicine used in China for a long history. Long-time or excessive use of realgar causes liver injury. However, its underlying mechanism is not fully clarified. AIM OF THE STUDY: In this study, we investigated the toxic effect of sub-chronic exposure to realgar on mice liver, and further revealed its underlying mechanism focused on the TXNIP/NLRP3 pathway and bile acid homeostasis. MATERIAL AND METHODS: Mice were divided into control and different doses of sub-chronic realgar exposed groups. Total arsenic levels in the blood and liver were determined by atomic fluorescence spectrometry. The effect of realgar on liver function was evaluated by biochemical analysis and histopathological examination. Assay kits were applied for the measurement of oxidative stress indexes, MPO and plasma inflammatory cytokines. The mRNA and proteins involved in the TXNIP/NLRP3 and NF-κB pathways were determined by RT-qPCR, western blot, Immunofluorescence and Immunohistochemistry. UHPLC/MS/MS was used for the quantitative analysis of bile acids (BAs) in mice plasma, liver and urine. The genes related to BAs metabolism were measured by RT-qPCR. RESULTS: Sub-chronic exposure to realgar led to arsenic accumulation and caused oxidative damage and inflammatory infiltration in mouse liver, finally resulting in liver injury. Realgar treatment activated the NF-κB pathway and significantly upregulated the TXNIP/NLRP3 pathway in mouse liver. Realgar altered the metabolic balance of BAs, which is related to the abnormal expression of BAs transporters and enzymes. CONCLUSION: Sub-chronic exposure to realgar caused liver injury in mouse, and the mechanism may involve the upregulation of the TXNIP/NLRP3 pathway and disordered BAs homeostasis.

Meta-analysis and systematic review of acupotomy combined with puncture and moxibustion in the treatment of knee osteoarthritis.

BACKGROUND: This study aimed to systematically evaluate the therapeutic effects of acupotomy combined with acupuncture and moxibustion on knee osteoarthritis (KOA), which was expected to provide a reference for clinical treatment of KOA using traditional Chinese medicine (TCM). METHODS: The databases PubMed, Embase, Medline, Ovid, and Springer were searched to retrieve randomized controlled trials (RCTs) on KOA treatment by acupotomy combined with acupuncture and moxibustion. The search time was set as from the date the database was established to 31 December 2020. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was used to conduct bias risk assessment on the included literature, and Review Manager 5.3 software was used for meta-analysis. RESULTS: A total of 10 RCTs were included in this study, including 1,073 participants. Meta-analysis results showed that compared with the control group, the clinical treatment efficiency of the experimental group was higher [mean difference (MD) =5.72; 95% confidence interval (CI): 3.39 to 9.64; Z=6.54; P<0.00001], and the postoperative visual analogue scale (VAS) scores were reduced (MD =-1.72; 95% CI: -2.41 to -1.03; Z=4.86; P<0.00001). DISCUSSION: Acupotomy combined with acupuncture and moxibustion treatment for KOA can increase clinical treatment efficiency, and relieve postoperative pain, suggesting that the combination of acupotomy, acupuncture, and moxibustion has better therapeutic effects on KOA and can be promoted clinically.

[Molecular mechanism analysis of Erzhi Wan in treatment of aging based on network pharmacology].

This present study aimed to explore the molecular mechanism of Erzhi Wan(a prescription of nourishing Yin and toni-fying liver and kidney) in treatment of aging by network pharmacology. The active constituents and target proteins of Erzhi Wan were searched from Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and PubChem databases respectively. Aging-related genes were searched from Gene and HAGR databases. Based on the Ingenuity Pathway Analysis(IPA), we analyzed the common molecular network, biological pathway and interaction sites between these two parts, and verified some of them by Western blot. Twelve active constituents of Erzhi Wan were screened by TCMSP databases, 69 protein targets were predicted through PubChem, and 148 aging-related genes were found in Gene and HAGR databases. IPA comparison showed that the molecular networks of these two were complex, with diversity of biological functions. The common pathways involved 292 pathways, mainly related to tumors. They acted on hypoxia inducible factor-1α gene(HIF1α), nuclear factor-E2 related factor(Nrf2/NFE2 L2), tumor necrosis factor(TNF) and other sites. Western blot results suggested that Erzhi Wan could down-regulate the expression of HIF1α, with statistical difference(P<0.05). It was concluded that, Erzhi Wan could intervene aging through improving pseudo-hypoxic microenvironment and inflammation. The molecular mechanism of Erzhi Wan in delaying aging was preliminarily revealed, which laid a foundation for further stu-dying the anti-aging mechanism of Erzhi Wan, and also provided a reference for the compatibility mechanism and extended application of Chinese medicine compounds.

Identification of neurotoxicity markers induced by realgar exposure in the mouse cerebral cortex using lipidomics.

Realgar is a traditional Chinese medicine containing arsenic and has neurotoxicity. This study used realgar exposure mice model, neurobehavioral tests, analytical chemistry, molecular biology and nontargeted lipidomics to explore the mechanism of realgar damages the nervous system. The arsenic contained in realgar passed through the BBB and accumulated in the brain. Neurons, synapses and myelin showed abnormal changes in the cerebral cortex. The number of autophagosomes were incresed as well as levels of MDA, Lp-PLA2, and cPLA2 but the CAT level was significant reduced. Finally, the cognition and memory of mice were decreased. Nontargeted lipidomics detected 34 lipid subclasses including 1603 lipid molecules. The levels of the LPC and LPE were significantly increased. Under the condition of variable importance for the projection (VIP)>1 and P < 0.05, only 28 lipid molecules satisfied the criteria. The lipid molecular markers SM (d36:2), PE (18:2/22:6) and PE (36:3) which were filtered by receiver operating characteristic (ROC) curve (AUC>0.8 or AUC<0.2) were used to identify the neurotoxicity induced by realgar. Therefore, realgar induces neurotoxicity through exacerbating oxidative damage and lipid dysfunction. Providing research basis for the clinical diagnosis and treatment of realgar-induced neurotoxicity.

Effects of the New Lift-Thrust Operation in Laser Acupuncture Investigated by Thermal Imaging.

Acupuncture manipulation is one of the key factors affecting the performance of acupuncture in Traditional Chinese Medicine. Lift-thrust and twirl-twist are two of the most commonly used manipulation methods for needle acupuncture. We previously have developed a novel laser acupuncture model that emulates lift-thrust operation. In this study, we intend to show the effectiveness of such a model by applying it on the Neiguan acupoint (PC6). Stimulation was reported to be beneficial for improving cardiac output and peripheral circulation. Therefore, we hypothesized that the stimulation of laser acupuncture may increase the temperature of the subjects' fingertip due to increased peripheral blood flow. A thermal imager was used to measure the temperature change of subjects' fingertips. Through regression analysis, it has been shown that while PC6 is stimulated, laser acupuncture with lift-thrust operation caused a more rapid, stable, and lasting temperature rise of fingertip than that without lift-thrust operation. On the contrary, we observe no significant temperature change when a sham point nearby PC6 (a point which is not traditionally defined as the acupoint) was stimulated. Our results suggest the emulation of manipulation methods such as the lift-thrust operation could be a potential direction for the future development of laser acupuncture.

Exploration of the Hepatoprotective Effect and Mechanism of Swertia mussotii Franch in an Acute Liver Injury Rat Model.

BACKGROUND AND OBJECTIVE: Swertia mussotii Franch, also known as "Zangyinchen", is one of a Tibetan traditional herb used for treatment of liver diseases over thousands of years at Qinghai-Tibet Plateau, has been confirmed to be hepatoprotective. However, the underlying mechanism is largely unknown. MATERIALS AND METHODS: In this study, we evaluated the effect of S. mussotii treatment in a carbon tetrachloride-induced acute liver injury rat model by examining the serum alanine aminotransferase, aspartate aminotransferase, total bilirubin levels and performing histological observations of the liver tissues. Meanwhile, the metabolomics analysis was used to explore the molecular mechanism of S. mussotii treatment by high performance liquid chromatography tandem mass spectrometry. RESULTS: The results showed that S. mussotii treatment could effectively improve the serum alanine aminotransferase, aspartate aminotransferase, total bilirubin in acute liver injury rat model. Histological observation showed that S. mussotii treatment could effectively alleviate liver injury. Moreover, the metabolomics analysis showed that S. mussotii treatment could normalize the levels of many fatty acid metabolism related metabolites. And the results of pathway analysis showed that these metabolites significantly enriched in fatty acid biosynthesis pathway (myristic acid, dodecanoic acid and capric acid) and linoleic acid metabolism pathway (13-OxoODE). CONCLUSION: The results indicated that S. mussotii treatment could significantly improve acute liver injury through affecting the pathways related to lipid metabolism.

A Membrane-Targeted Peptide Inhibiting PtxA of Phosphotransferase System Blocks Streptococcus mutans.

Streptococcus mutans, the primary cause of dental caries, takes up carbohydrates through the phosphoenolpyruvate sugar phosphotransferase system (PTS). This study aimed to identify a novel membrane-targeted antimicrobial peptide (AMP) that could also target the L-ascorbate-specific PtxA component of the S. mutans PTS system. C10-KKWW was identified and selected using virtual screening of a lipopeptide library, a minimum inhibiting concentration (MIC) assay, cytotoxicity assays and a hemolysis assay. Surface plasmon resonance confirmed that C10-KKWW had a high binding affinity for PtxA. Combining with scanning electron microscopy and cell permeability assay, it was shown that the effects of C10-KKWW could be attributed to both membrane and PtxA. Wild type (WT) S. mutans, a ptxA deletion mutant (ΔptxA), and a mutant-complemented strain (CptxA), were cultured consistently in brain heart infusion (BHI) medium, tryptone-vitamin medium supplemented with 15 mM L-ascorbate (TVL), or for 5 h in BHI supplemented with 7.4 mM sodium L-ascorbate. Compared to ∆ptxA, in WT S. mutans and CptxA, C10-KKWW had a stronger MIC (3.9 µg/mL), and distinctively decreased biofilm viability. The extracellular concentrations of L-ascorbate/sodium L-ascorbate were not changed before and after WT treated with C10-KKWW. L-ascorbate-induced operon genes, or other PTS genes, were significantly suppressed by C10-KKWW. In conclusion, C10-KKWW has been developed; it acts through interaction with the bacterial membrane and interferes with L-ascorbate translocation to inhibit S. mutans growth and eradicate its biofilm. C10-KKWW may be especially effective at optimal oral ascorbate levels. A combination of C10-KKWW with sodium L-ascorbate might also be a novel strategy for dental caries treatment.

Modulation of Spectral Power and Functional Connectivity in Human Brain by Acupuncture Stimulation.

Acupuncture, as an external stimulation, can produce clinical effects via the central nervous system. In order to investigate the modulatory efficacy of acupuncture on brain activity, multichannel EEG signals evoked by acupuncture at "Zusanli" acupoint were recorded from healthy humans in three states: pre-acupuncture, acupuncture, and post-acupuncture. Power spectral density is first used to analyze the EEG power change during acupuncture process. It is found that EEG power significantly increased in the delta and alpha bands under acupuncture and high power level remained in alpha band after acupuncture. Then, we calculated phase lag index to quantify the phase synchronization of pair-wise channels. In acupuncture state, delta and alpha bands exhibit significantly higher synchronization degree than pre-acupuncture state. Additionally, post-effect of acupuncture can be observed in alpha band as high synchronization degree remains in post-acupuncture state. Moreover, functional brain networks converted from synchronization matrix in each band are reconstructed. Acupuncture increases long-range connections between left and right hemispheres and changes the position of main nodes. Graph theory metrics are extracted to explore the change of functional connectivity in different states. The result shows the functional networks in delta and alpha bands are small world networks (SWN) and acupuncture improves the SWN efficiency of functional network.