Programmed pH-responsive core-shell nanoparticles for precisely targeted therapy of ulcerative colitis.

pH-Responsive nanotherapeutics were recently developed for the treatment of ulcerative colitis (UC). However, they target the entire colon rather than the UC site, which leads to insufficient accumulation in inflamed colon lesions and causes side effects. Core-shell nanoparticles exhibit unique advantages in improving the precision of targeted delivery. In this study, Eudragit® EPO and L100, two pH-sensitive materials, were coated on nano-sized curcumin to fabricate core-shell nanoparticles. The developed CNs@EPO@L100 exhibited programmed pH-responsive drug release behavior, improved in vitro anti-inflammatory ability, and enhanced accumulation at the site of inflammation in the colon. Furthermore, after oral administration, CNs@EPO@L100 significantly ameliorated the inflammatory symptoms in mice. Taken together, this study provides insights into programmed release through the rational application of pH-sensitive materials and offers strategies for a precisely targeted therapy of UC using core-shell nanoparticles.

Anti-cancer Potential of Polysaccharide Extracted From Polygonatum sibiricum on HepG2 Cells via Cell Cycle Arrest and Apoptosis.

Polygonatum sibiricum is one of the most widely used traditional Chinese medicine in China. Polygonatum sibiricum polysaccharide (PSP) is the main functional component of Polygonatum sibiricum. In this study, a water-soluble polysaccharide (PSP-1) was first isolated from Polygonatum sibiricum with a molecular weight of 38.65 kDa. Structural analysis was performed via methylation and FT-IR spectroscopy analyses, which in combination with NMR spectroscopy, revealed that PSP-1 has a → 4-α-D-Glcp-1 → backbone with the substitution at O-6 with the ß-D-Glcp-1 → residues. Furthermore, PSP-1 exhibited potent and concentration-dependent anticancer effects, inducing HepG2 cell apoptosis and arresting the cell cycle at the G1 phase. Moreover, PSP-1 also decreased the mitochondrial membrane potential, damaged the nucleus of HepG2 cells, and increased the activity of caspase-9 and-3 in the intrinsic apoptotic pathways to induce HepG2 cell apoptosis. To conclude, PSP-1 might be a good candidate for the treatment of liver cancer, and this work provides important information for understanding the relationship between structure and antitumor activity of PSP-1, which is relevant for the treatment of hepatocellular carcinoma in clinic.

Integrated Traditional Chinese Medicine Improves Functional Outcome in Acute Ischemic Stroke: From Clinic to Mechanism Exploration With Gut Microbiota.

As a life-threatening disease, stroke is the leading cause of death and also induces adult disability worldwide. To investigate the efficacy of the integrated traditional Chinese medicine (ITCM) on the therapeutic effects of acute ischemic stroke (AIS) patients, we enrolled 26 patients in the ITCM [Tanhuo decoction (THD) + Western medicine (WM)] group and 23 in the WM group. Thirty healthy people were also included in the healthy control (HC) group. ITCM achieved better functional outcomes than WM, including significant reduction of the phlegm-heat syndrome and neurological impairment, and improvement of ability. These facts were observed in different pretreatment gut enterotypes. In this paper, we collected the stool samples of all participants and analyzed the 16S rRNA sequence data of the gut microbiota. We identified two enterotypes (Type-A and Type-B) of the gut microbial community in AIS samples before treatment. Compared to Type-B, Type-A was characterized by a high proportion of Bacteroides, relatively high diversity, and severe functional damage. In the ITCM treatment group, we observed better clinical efficacy and positive alterations in microbial diversity and beneficial bacterial abundance, and the effect of approaching healthy people's gut microbiota, regardless of gut enterotypes identified in pretreatment. Furthermore, we detected several gut microbiota as potential therapeutic targets of ITCM treatment by analyzing the correlations between bacterial abundance alterations and functional outcomes, where Dorea with the strongest correlation was known to produce anti-inflammatory metabolite and negatively linked to trimethylamine-N-oxide (TMAO), a biomarker of AIS. This study analyzed clinical and gut microbial data and revealed the possibility of a broad application independent of the enterotypes, as well as the therapeutic targets of the ITCM in treating AIS patients with phlegm-heat syndrome.

Anti-inflammatory effect of Ailanthus altissima (Mill.) Swingle leaves in lipopolysaccharide-stimulated astrocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Activated astrocytes are involved in the progression of neurodegenerative diseases. Traditionally, Ailanthus altissima (Mill.) Swingle, widely distributed in East Asia, has been used as a medicine for the treatment of fever, gastric diseases, and inflammation. Although A. altissima has been reported to play an anti-inflammatory role in peripheral tissues or cells, its role in the central nervous system (CNS) remains unclear. AIM OF THE STUDY: In the present study, we investigated the anti-inflammatory effects and mechanism of action of A. altissima in primary astrocytes stimulated by lipopolysaccharide (LPS). MATERIALS AND METHODS: A nitrite assay was used to measure nitric oxide (NO) production, and the tetrazolium salt 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to determine cytotoxicity. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) were determined with western blotting. Reverse-transcription PCR was used to assess the expression of inflammatory cytokines. The levels of reactive oxygen species were measured using 2,7-dichlorodihydrofluorescein diacetate. Luciferase assay and immunocytochemistry were used for assessing nuclear factor-kappa B (NF-κB) transcription and p65 localization, respectively. Memory and social interaction were analyzed using the Y-maze and three-chamber tests, respectively. RESULTS: The ethanol extract of A. altissima leaves (AAE) inhibited iNOS and COX-2 expression in LPS-stimulated astrocytes. Moreover, AAE reduced the transcription of various proinflammatory mediators, hindered NF-κB activation, and suppressed extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activation without p38 activation. Ultra-high performance liquid chromatography with mass spectrometry analysis revealed that AAE comprised ethyl gallate, quercetin, and kaempferol, along with luteolin, which has anti-inflammatory properties, and repressed LPS-induced nitrite levels and the nuclear translocation of p65. Finally, oral administration of AAE attenuated LPS-induced memory and social impairment in mice and repressed LPS-induced ERK and JNK activation in the cortices of mice. CONCLUSION: AAE could have therapeutic uses in the treatment of neuroinflammatory diseases via suppression of astrocyte activation.

Gut Microbiota-Related Effects of Tanhuo Decoction in Acute Ischemic Stroke.

Acute ischemic stroke (AIS) is a major cause of acquired adult disability and death. Our previous studies proved the efficacy and effectiveness of Tanhuo decoction (THD) on AIS. However, the therapeutic mechanism remains unclear. We recruited 49 AIS patients and 30 healthy people to explore the effects of THD+basic treatment on the poststroke gut microbiota of AIS patients using 16S rRNA sequencing, in which 23 patients received basic treatment (control group) and 26 patients received THD+basic treatment (THD group). By comparing the data before and after treatments, we found the THD group acquired better outcome than the control group on both clinical outcome indices and the characteristics of gut microbiota. In addition to the mediation on short-chain fatty acid- (SCFA-) producing bacteria in two groups, treatment in the THD group significantly decreased the lipopolysaccharide- (LPS-) producing bacteria to reduce LPS biosynthesis. Besides, the complexity of the cooccurrence of gut microbiota and the competition among LPS-producing bacteria and opportunistic pathogenetic bacteria were enhanced in the THD group. Treatment in the THD group also exhibited the potential in decreasing genes on the biosynthesis of trimethylamine (TMA), the precursor of Trimethylamine N-oxide (TMAO), and increasing genes on the degradation of TMA, especially increasing trimethylamine-corrinoid protein Co-methyltransferase (mttB) which catabolizes TMA to methane. These results hinted that THD+basic treatment might exert its efficacy by mediating the gut microbiota and microbial metabolites, including LPS and TMAO that aggravate the sterile inflammation and platelet aggregation. Moreover, the well-fitting regression model results in predicting the clinical outcome with the alteration of gut microbiota proved gut microbiota as a potential indicator of AIS and provided evidence of the communication between the gut and brain of AIS patients.

Structural, rheological properties and antioxidant activities of polysaccharides from mulberry fruits (Murus alba L.) based on different extraction techniques with superfine grinding pretreatment.

The structural characteristics and biological activity of polysaccharides were influenced by different extraction methods. In this study, polysaccharides from mulberry fruits (Murus alba L., which were pre-treated with superfine grinding process) (MFP) were exacted using hot-water extraction (HWE), enzyme-assisted hot water extraction (EAHE), ultrasonic-assisted hot water extraction (UAHE), and high-speed shear homogenization-assisted hot water extraction (HSEHE). The extraction yield, structure, rheological properties and antioxidant activities of MFPs were investigated. MFP extracted using the HSEHE method have the highest extraction yields than other extraction methods. The smaller particle size of mulberry powder was found to improve the extraction yields. The MFPs were obtained by the combination between different extraction methods and superfine grinding pretreatment (through 100 mesh sieve) (MFP-HWE100, MFP-EAHE100, MFP-UAHE100, MFP-HSEHE100) showed the same levels of monosaccharide compositions and glycosyl linkages, However, these methods can produce MFP with different monosaccharide proportions, branching degree, different molecular weight, particle size and microstructure. MFP-HSEHE100 achieved the lowest molecular weight and particle size, which exhibited better thixotropy and antioxidant activities than other MFPs. This study identified that HSEHE was the most suitable extraction method for MFP.

Strategies for Remodeling the Tumor Microenvironment Using Active Ingredients of Ginseng-A Promising Approach for Cancer Therapy.

The tumor microenvironment (TME) plays a key role in promoting the initiation and progression of tumors, leading to chemoradiotherapy resistance and immunotherapy failure. Targeting of the TME is a novel anti-tumor therapeutic approach and is currently a focus of anti-tumor research. Panax ginseng C. A. Meyer (ginseng), an ingredient of well-known traditional Asia medicines, exerts beneficial anti-tumor effects and can regulate the TME. Here, we present a systematic review that describes the current status of research efforts to elucidate the functions and mechanisms of ginseng active components (including ginsenosides and ginseng polysaccharides) for achieving TME regulation. Ginsenosides have variety effects on TME, such as Rg3, Rd and Rk3 can inhibit tumor angiogenesis; Rg3, Rh2 and M4 can regulate the function of immune cells; Rg3, Rd and Rg5 can restrain the stemness of cancer stem cells. Ginseng polysaccharides (such as red ginseng acidic polysaccharides and polysaccharides extracted from ginseng berry and ginseng leaves) can regulate TME mainly by stimulating immune cells. In addition, we propose a potential mechanistic link between ginseng-associated restoration of gut microbiota and the tumor immune microenvironment. Finally, we describe recent advances for improving ginseng efficacy, including the development of a nano-drug delivery system. Taken together, this review provides novel perspectives on potential applications for ginseng active ingredients as anti-cancer adjuvants that achieve anti-cancer effects by reshaping the tumor microenvironment.

Nonvolatile Electrically Reconfigurable Integrated Photonic Switch Enabled by a Silicon PIN Diode Heater.

Reconfigurability of photonic integrated circuits (PICs) has become increasingly important due to the growing demands for electronic-photonic systems on a chip driven by emerging applications, including neuromorphic computing, quantum information, and microwave photonics. Success in these fields usually requires highly scalable photonic switching units as essential building blocks. Current photonic switches, however, mainly rely on materials with weak, volatile thermo-optic or electro-optic modulation effects, resulting in large footprints and high energy consumption. As a promising alternative, chalcogenide phase-change materials (PCMs) exhibit strong optical modulation in a static, self-holding fashion, but the scalability of present PCM-integrated photonic applications is still limited by the poor optical or electrical actuation approaches. Here, with phase transitions actuated by in situ silicon PIN diode heaters, scalable nonvolatile electrically reconfigurable photonic switches using PCM-clad silicon waveguides and microring resonators are demonstrated. As a result, intrinsically compact and energy-efficient switching units operated with low driving voltages, near-zero additional loss, and reversible switching with high endurance are obtained in a complementary metal-oxide-semiconductor (CMOS)-compatible process. This work can potentially enable very large-scale CMOS-integrated programmable electronic-photonic systems such as optical neural networks and general-purpose integrated photonic processors.

Alisol A is potentially therapeutic in human breast cancer cells.

Recent developments in breast cancer therapy have significantly improved patient survival rate; however, recurrence remains a major problem. Systemic treatment of breast cancer with available therapies is not curative. Natural products can be potentially used for treating cancer. Recently, a wide range of pharmacological activities has been reported for Alismatis Rhizoma, a popular traditional Chinese medicine. However, the mechanisms via which its compounds act on breast cancer remain unclear. The present study aimed to investigate the potential of natural therapeutic agents from Alismatis Rhizoma for treating breast cancer. Human breast cancer MDA­MB­231 cells were treated with four main protostane triterpenes from Alismatis Rhizoma, including alisol A, alisol A 24­acetate, alisol B and alisol B 23­acetate. Among these, alisol A significantly inhibited cell viability. Alisol A induced cell apoptosis, G1 phase cell cycle arrest, autophagy, and intracellular reactive oxygen species (ROS) generation in MDA­MB­231 cells. The number of APE1­/γH2AX­/LC3­II positive cells was also significantly higher compared with that of negative control cells. All these results were dose­dependent. Cleaved caspase­3, cleaved caspase 9, Bcl­2, and p­p38 expression indicated cell apoptosis after alisol A treatment. The changes in cyclin A and cyclin D1 expression was associated with cell cycle arrest upon alisol A treatment. Furthermore, LC3­II expression upon alisol A treatment was indicative of autophagy. Alisol A treatment can induce autophagy­dependent apoptosis in human breast cancer cells via induction of ROS and DNA damage. Thus, Alisol A might serve as a new therapeutic agent against breast cancer.

The formation process of green substances in Chrysanthemum morifolium tea.

One interesting phenomenon of Chrysanthemum morifolium tea is its formation of a green or dark green color after hours of brewing, and it is important to study the compounds that form this color and whether they might be involved in health benefits. Non-targeted metabolomics could clearly distinguish between green and non-green species by sparse partial least squares discriminant analysis (sPLS-DA) and heat-mapping. We found that the pH was the primary factor in the formation of the green color. Two green precursors (GP1 and GP2) were separated and purified with preparative HPLC. FT-IR analysis and the saccharide content analysis showed that GP1 had the typical characteristics of saccharides. GP2 was identified as chlorogenic acid by ESI-Q-TOF/MS and NMR. We raised the formation process of green substances was caused by the hydrolysates of chlorogenic acid reacting with glycosides or groups attached to the saccharides, which suggests a new mechanism for color-forming reactions.

Coptisine ameliorates renal injury in diabetic rats through the activation of Nrf2 signaling pathway.

The present study has been designed and carried out to evaluate the potential of coptisine on diabetic nephropathy. Diabetes was induced in SD rats through one single intraperitoneal injection of streptozotocin (65 mg/kg) method, and then diabetic rats were orally administered with 25 mg/kg/day coptisine or 50 mg/kg/day coptisine for 8 weeks. Severe impairment of renal function in rats with diabetes was observed as indicated by increased urine protein excretion, kidney hypertrophy index, serum creatinine level, and blood urea nitrogen level. Oxidative stress damage was observed as indicated by increased levels of reactive oxygen species, malondialdehyde, and decreased levels of glutathione, superoxide dismutase, and catalase. However, these alterations in kidneys of rats with diabetes were alleviated by administration of coptisine. Furthermore, the expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and its targeted antioxidative genes heme oxygenase 1 and NADPH quinone oxidoreductase 1 in the diabetic kidneys were significantly increased after coptisine treatment. These results suggested that coptisine ameliorated oxidative renal injury in diabetic rats, and the possible mechanisms for the renoprotective effects of coptisine may be related to activation of the Nrf2 signaling pathway.

Analysis of the chemical components of Qixianqingming granules and their metabolites in rats by UPLC-ESI-Q-TOF-MS.

Qixianqingming granules (QXQM) comprise a traditional Chinese medicine (TCM) formula that was developed based on the combination of TCM theory and clinical practice. This formula has been proven to effectively treat asthma. In this study, an analytical procedure using ultraperformance liquid chromatography, coupled with electrospray ionization quadrupole time-of-flight mass spectrometry, was established for the rapid separation and sensitive identification of the chemical components in QXQM and its metabolites in serum of rats. Seventy-two compounds were systematically identified in QXQM, including flavonoids, terpenoids, anthraquinones, phenylethanoid glycosides, stilbenes, alkaloids, and organic acids. Thirteen prototype compounds and 29 metabolites were detected in the serum of rats. The results provided fundamental information for further studying the mechanisms and clinical application of QXQM.

Effects of a Modified Tai Chi Program on Older People with Mild Dementia: A Randomized Controlled Trial.

BACKGROUND: Tai Chi exercise is a non-pharmacological therapy that has received increased attention in recent years. A Tai Chi program has been specifically modified for older people with cognitive impairments by the research team. OBJECTIVE: We aim to assess the effects of this Tai Chi program on mild dementia. METHODS: Eighty older people with mild dementia were recruited and randomly assigned to a Tai Chi group or a control group. The Tai Chi group practiced the Tai Chi program three times a week for 10 months, while the control group continued receiving routine treatments. All participants were assessed for cognitive function, behavior/mood, and activities of daily living at baseline, 5 months, and 10 months. RESULTS: The Tai Chi group performed better than the control group. Repeated measures ANOVA revealed a significant group×time interaction in the Montreal Cognitive Assessment (MoCA). Further analysis of sub-items of the MoCA showed a significant time effect in naming and abstraction. It was statistically significant in both main effect of time and group×time interaction in the Neuropsychiatric Inventory (NPI) and Geriatric Depression Scale (GDS). Paired sample t test showed the Tai Chi group scored lower at 5 and 10 months in the NPI and at 10 months in the GDS compared with baseline. The Tai Chi group scored lower than the control group at 10 months in the NPI and GDS. CONCLUSION: The results suggest this Tai Chi program may help improve cognitive function and mental well-being for older adults with mild dementia.

Polyethylenimine Hybrid Thin-Shell Hollow Mesoporous Silica Nanoparticles as Vaccine Self-Adjuvants for Cancer Immunotherapy.

Conventional adjuvants (e.g., aluminum) are insufficient to trigger cell-mediated immunity, which plays a crucial role in triggering specific immunity against cancer. Therefore, developing appropriate adjuvants for cancer vaccines is a central way to stimulate the antitumor immune response. Hollow mesoporous silica nanoparticles (HMSNs) have been proven to stimulate Th1 antitumor immunity in vivo and promote immunological memory in the formulation of novel cancer vaccines. Yet, immune response rates of existing HMSNs for anticancer immunity still remain low. Here, we demonstrate the generation of polyethylenimine (PEI)-incorporated thin-shell HMSNs (THMSNs) through a facile PEI etching strategy for cancer immunotherapy. Interestingly, incorporation of PEI and thin-shell hollow structures of THMSNs not only improved the antigen-loading efficacy and sustained drug release profiles but also enhanced the phagocytosis efficiency by dendritic cells (DCs), enabled DC maturation and Th1 immunity, and sustained immunological memory, resulting in the enhancement of the adjuvant effect of THMSNs. Moreover, THMSNs vaccines without significant side effects can significantly reduce the potentiality of tumor growth and metastasis in tumor challenge and rechallenge models, respectively. THMSNs are considered to be promising vehicles and excellent adjuvants for the formulation of cancer vaccines for immunotherapy.

The formation and bioactivities of green substances in Chrysanthemum morifolium tea.

One interesting phenomenon of Chrysanthemum morifolium tea is its formation of green or dark green color after hours of brewing. We investigated the greening reaction and its bioactivities, including an analysis of the green compounds. Results showed that the green color was due to a decrease in the L* (lightness), b* (yellowness/blueness), chroma values and an increase in hue angle. The green substances were found to be substances with similar polarities and unstable in acidic conditions. There was no significant difference (p < 0.01) in antioxidant activity between non-green and green samples. The green substances did not lead to cytotoxicity in PC12 cells at low concentrations, but at high concentrations, they caused a significant (p < 0.01) decrease in cell viability. The saccharide percentage and FT-IR results showed that the greening reaction was affected by the glycosides or groups attached to the saccharides, which might suggest a new mechanism for color-forming reactions.

Effect of Weakly Basic Conditions on the Separation and Purification of Flavonoids and Glycosides from Chrysanthemum morifolium Tea.

Tea brewed from chrysanthemum flowers has been widely used in Chinese medicine. The possibly medicinal compounds in Chrysanthemum morifolium tea can be purified by preparative high performance liquid chromatography (HPLC), but this is usually done with acidic conditions, which leads to the hydrolysis of glycosides. In hopes of avoiding this hydrolysis, we explored the effect of weakly basic conditions on the separation and purification of flavonoids and glycosides from Chrysanthemum morifolium. We also explored the effects of weakly basic conditions on chlorogenic acid (3-CQA) and apigenin-7-O-glucoside (A7G). Our results show that the concentration of the weakly basic ammonium hydrogen carbonate and time had no significant effect on A7G, p < 0.01, but it had a significant effect on 3-CQA, p < 0.01. HPLC and ultraviolet (UV) analysis showed that the structure of 3-CQA is destroyed in weakly basic conditions. Caffeic acid, quinic acid, and 3,4-dihydroxymandelic acid, which is a hydrolysate of 3-CQA, were identified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The results showed that weakly basic conditions could be used for the purification of flavonoids and glycosides but not for caffeoylquinic acids. Moreover, our work clarified the hydrolysis behaviour of caffeoylquinic acids, which can be helpful for research into their functional aspects.

The Effects of Music Therapy on Cognition, Psychiatric Symptoms, and Activities of Daily Living in Patients with Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia, affecting millions of older people worldwide. However, pharmacological therapies have not achieved desirable clinical efficacy in the past decades. Non-pharmacological therapies have been receiving increased attention to treat dementia in recent years. OBJECTIVE: This study explores the effects of music therapy on cognitive function and mental wellbeing of patients with AD. METHODS: A total number of 298 AD patients with mild, moderate, or severe dementia participated in the study. The participants with each grade of severity were randomly divided into three groups, which were a singing group, a lyric reading group, and a control group. These three groups received different interventions for three months. All participants underwent a series of tests on cognitive functions, neuropsychological symptoms, and activities of daily living at baseline, three months, and six months. RESULTS: The analysis shows that music therapy is more effective for improving verbal fluency and for alleviating the psychiatric symptoms and caregiver distress than lyrics reading in patients with AD. Stratified analysis shows that music therapy is effective for enhancing memory and language ability in patients with mild AD and reducing the psychiatric symptoms and caregiver distress in patients with moderate or severe AD. However, no significant effect was found for activities of daily living in patients with mild, moderate, or severe AD. CONCLUSION: This study suggests that music therapy is effective in enhancing cognitive function and mental wellbeing and can be recommended as an alternative approach to manage AD associated symptoms.

Efficacy of practising Tai Chi for older people with mild dementia: protocol for a randomised controlled study.

INTRODUCTION: Many studies suggest that Tai Chi exercise is a safe and appropriate mind-body exercise for older people and effectively slows down age-related cognitive decline. A set of bespoke Tai Chi exercise named 'Cognition Protecting Tai Chi' (CPT) has been created for older people with cognitive impairments by the research team of geriatricians, neurologists, rehabilitation specialists, experts of sports medicine and experienced practitioners of traditional Chinese medicine. This trial is designed to evaluate its effects on cognitive function, behaviour/moods, risk of falls and activities of daily living of the participants with mild dementia. METHODS AND ANALYSIS: A randomised controlled study will be conducted. Eighty participants with mild dementia will be recruited and randomly allocated to an intervention group and a control group. The intervention group will practice the CPT exercise three times a week for 20 min each time under the guidance of professional therapists. The control group will continue receiving their routine treatments. The duration of this study will be 10 months. All participants will be assessed with a battery of neuropsychological and functional evaluations, which include Mini Mental State Examination, Montreal Cognitive Assessment, the WHO-University of California Los Angeles-Auditory Verbal Learning test (WHO-UCLA-AVLT), Trail Making Test (TMT), Geriatric Depression Scale, Neuropsychological Inventory and Barthel Index, at the baseline, 5 and 10 months during the study period. Fall incident will also be recorded. The primary outcome will be the WHO-UCLA-AVLT delayed recall score. The secondary outcome will be the TMT score. ETHICS AND DISSEMINATION: This study has been approved by the ethical review committee of the Beijing Geriatric Hospital (protocol number: 2015-021). Informed consent will be obtained from all participants or their guardians. The authors intend to submit the findings of the study to peer-reviewed journals or academic conferences to be published. TRIAL REGISTRATION NUMBER: ChiCTR-INR-16009872; Pre-results.

Increased Efficacy of Antivenom Combined with Hyperbaric Oxygen on Deinagkistrodon acutus Envenomation in Adult Rats.

BACKGROUND: Snakebites are a neglected threat to global human health with a high morbidity rate. The present study explored the efficacy of antivenom with hyperbaric oxygen (HBO) intervention on snakebites, which could provide the experimental basis for clinical adjuvant therapy. METHODS: Male Sprague-Dawley rats (n = 96) were randomized into four groups: the poison model was established by injecting Deinagkistrodon acutus (D. acutus) venom (0.8 LD50) via the caudal vein; the antivenom group was injected immediately with specific antivenom via the caudal vein after successful establishment of the envenomation model; and the antivenom + HBO group was exposed to HBO environment for 1 h once at predetermined periods of 0 h, 4 h, 12 h, and 23 h after antivenin administration. Each HBO time point had six rats; the control group was left untreated. The rats in the experimental group were euthanized at the corresponding time points after HBO therapy, and brain tissue and blood were harvested immediately. Hematoxylin and eosin (H&E) staining was used to investigate the pathological changes in the rat brain. Immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), and Western blotting were used to detect the expression of Nestin mRNA and protein in the subventricular zone (SVZ) of the brain. The levels of coagulation function (prothrombin time, activated partial thromboplastin time [APTT], and fibrinogen) and oxidation/antioxidation index (malondialdehyde [MDA] and superoxide dismutase [SOD]) were analyzed. Data were analyzed using one-way analysis of variance. RESULTS: The brain tissue from rats in the poison model was observed for pathological changes using H&E staining. Tissues showed edema, decreased cell number, and disordered arrangement in the SVZ in the snake venom group. The antivenom - HBO intervention significantly alleviated these observations and was more prominent in the antivenom + HBO group. The serum levels of SOD and MDA in the snake venom group were increased and the antivenom - HBO intervention further increased the SOD levels but significantly decreased the MDA levels; however, this was enhanced within 1 h after HBO administration (MDA: F = 5.540, P = 0.008, SOD: F = 7.361, P = 0.000). Activated partial thromboplastin time (APTT) was significantly abnormal after venom administration but improved after antivenom and was even more significant in the antivenom + HBO group 5 h after envenomation (F = 25.430, P = 0.000). Only a few nestin-positive cells were observed in the envenomation model. The expression levels were significant in the antivenom and antivenom + HBO groups within 1 and 5 h after envenomation and were more significant in the antivenom + HBO group as determined by IHC, real-time PCR, and Western blotting (P < 0.05). D. acutus envenomation has neurotoxic effects in the brain of rats. CONCLUSIONS: Antivenin and HBO, respectively, induced a neuroprotective effect after D. acutus envenomation by attenuating brain edema, upregulating nestin expression in SVZ, and improving coagulopathy and oxidative stress. The intervention efficacy of antivenom with HBO was maximum within 5 h after envenomation and was more efficacious than antivenom alone.

Tanshinone IIA attenuates nerve transection injury associated with nerve regeneration promotion in rats.

Tanshinone IIA (Tan IIA) is the major pharmacological constituent of Salvia miltiorrhiza Bunge (Danshen) for the therapeutic purpose of preventing ischemic injury and treating cerebrovascular disease. The aim of the present study was to explore the potential neuroprotective effects of Tan IIA in sciatic nerve transection injury. We investigated the possible beneficial effects of Tan IIA in promoting nerve regeneration after nerve transection injury in rats. Nerve transection injury was induced in male Sprague-Dawley rats by left sciatic nerve transection. After neuroanastomosis, the rats were intraperitoneally (IP) injected with 6mg/kg, 15mg/kg, or 40mg/kg Tan IIA once daily for 12 weeks; the vehicle and positive control groups were injected with normal saline and mecobalamin (MeCbl, 100µg/kg), respectively. Axonal regeneration and functional recovery were evaluated by a range of morphological and functional measures 12 weeks after neuroanastomosis. The administration of 15mg/kg and 40mg/kg Tan IIA and MeCbl achieved better axonal regeneration with significant restoration of motor function as well as a marked decrease in Fluoro-Gold (FG)-labeled neurons and increased nerve regeneration. At 12 weeks post-surgery, 40mg/kg Tan IIA showed a better neuroprotective effect than 15mg/kg Tan IIA and MeCbl. There were no statistical differences between the 15mg/kg Tan IIA and MeCbl groups or the control and 6mg/kg Tan IIA groups. Our findings demonstrate that Tan IIA can alleviate nerve injury and promote nerve regeneration in a sciatic nerve transection model in rats, providing supportive evidence for Tan IIA as an effective potential therapeutic remedy for peripheral nerve injury.