Modified ZIF-8 Nanoparticles for Targeted Metabolic Treatment of Acute Spinal Cord Injury.

The activation of proinflammatory M1-type macrophages in the injured lesion accelerates the progression of a spinal cord injury (SCI). However, adverse side effects during systemic treatments targeting M1 macrophages have limited their applications. Nanoplatforms are novel carriers of traditional Chinese medicine because of their great efficiency to deliver and accumulation in the lesion. Herein, we synthesized a modified zeolitic imidazolate framework-8 (ZIF-8) nanoplatform for internalization and accumulation in the injured spinal cord and effective administration for SCI. In vitro and in vivo experiments suggested that Prussian blue and Schisandrin B modified ZIF-8 effectively accumulated in M1 macrophages, inhibited reactive oxygen species (ROS), and polarized the macrophage from proinflammatory M1 to anti-inflammatory M2 for rapid tissue infiltration by reprogramming the metabolic macrophages phenotype. This nanoplatform achieves a synergistic therapeutic effect of immunomodulation and neuroprotection, thereby shedding new light on the application of ZIF-8, and provides great potential for SCI.

Tumor-associated macrophages in tumor progression and the role of traditional Chinese medicine in regulating TAMs to enhance antitumor effects.

Purpose: To emphasize the importance of tumor-associated macrophages (TAMs) in tumor immunity and to describe the ways in which extracts from Traditional Chinese Medicine (TCM) achieve tumor therapy by modulating macrophages. Significance: By summarizing these available data, this review focused on TAMs and TCM and can build the foundation for future research on antitumor therapeutics. Methods: In this review, we summarized the key functions of TAMs in cancer development and overviewed literature on TCM targeting TAMs together with other immune cells aiming to enhance antitumor immunity. Conclusions: With an indispensable role in antitumor immunity, TAMs contribute to tumor progression, migration, invasion, angiogenesis, lymphangiogenesis, and immunosuppressive microenvironment. In recent years, TCM has gradually gained attention as a potential antitumor adjunctive therapy in preclinical and clinical trials. TCM is also a regulator of cytokine secretion and cell surface molecule expression in balancing the tumor microenvironment (TME), especially macrophage activation and polarization. Therefore, it is believed that TCM could serve as modifiers with immunomodulatory capability.

Mongolian Medicine Areca Thirteen Pill (GY-13) Improved Depressive Syndrome via upregulating cAMP/PKA/CREB/BDNF signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Areca Thirteen Pill, also called Gao You-13 (GY-13), is a traditional Mongolian herbal formula and has been extensively used to treat depression in Mongolian areas, which belongs to Heyi disease in Mongolian medicine. Major depressive disorder is a serious psychiatric disease, only one-third of individuals with depression are responsive to current antidepressants in clinic. Growing attention has been attracted by traditional herbal medicines in fighting depression because they are considered safer alternatives to pharmacotherapy. AIM OF THE STUDY: To reveal the mechanism of GY-13 in the treatment of depression. MATERIALS AND METHODS: The rat depression model was established by chronic unpredictable mild stress (CUMS), and primary hippocampal neurons were used to construct a glutamate-induced excitotoxicity model. The antidepressant effect of GY-13 was then assessed by performing sucrose preference tests, open field tests, and body weight measurements on rats. The expression of cAMP and PKA, mRNA levels of brain-derived neurotrophic factor (BDNF) and cAMP response element binding protein (CREB), and hippocampal neuronal apoptosis were measured. RESULTS: The results indicate that GY-13 significantly improves depression-like behavior, rescues decreased cAMP， PKA, recovers the mRNA levels of CREB and BDNF, and increases the proliferative activity of hippocampus. In addition, blockade of PKA reverses the effects of GY-13 treatment on CREB mRNA, BDNF mRNA levels. In vitro, GY-13 treatment increased hippocampal proliferative activity and attenuated Glu-induced apoptosis of hippocampal neurons as well as reduced CREB mRNA and BDNF mRNA expression levels. CONCLUSIONS: Our research demonstrated that GY-13 treatment exerted a potent antidepressant action via activation of cAMP/CREB/BDNF signaling pathway, promoting proliferation, and suppressing apoptosis. This research provides molecular biological ground for developing GY-13 into a potent alternative for the intervention of depression.

Research Progress on the Mechanism of the Acupuncture Regulating Neuro-Endocrine-Immune Network System.

As one of the conventional treatment methods, acupuncture is an indispensable component of Traditional Chinese Medicine. Currently, acupuncture has been partly accepted throughout the world, but the mechanism of acupuncture is still unclear. Since the theory of the neuro-endocrine-immune network was put forward, new insights have been brought into the understanding of the mechanism of acupuncture. Studies have proven that acupuncture is a mechanical stimulus that can activate local cell functions and neuroreceptors. It also regulates the release of related biomolecules (peptide hormones, lipid hormones, neuromodulators and neurotransmitters, and other small and large biomolecules) in the microenvironment, where they can affect each other and further activate the neuroendocrine-immune network to achieve holistic regulation. Recently, growing efforts have been made in the research on the mechanism of acupuncture. Some researchers have transitioned from studying the mechanism of acupuncture as a single linear pathway to using systems approaches, including metabolomics, genomics, proteomics and biological pathway analysis. This review summarizes the research progress on the neuro-endocrine-immune network related mechanism of acupuncture and discusses its current challenges and future directions.

Fermented Deer Blood Ameliorates Intense Exercise-Induced Fatigue via Modulating Small Intestine Microbiota and Metabolites in Mice.

Intense and excessive exercise-induced fatigue has become an important health issue and can damage intestinal health. Deer blood, as a food byproduct with nutritional value, has been found to restore physical strength. However, little is known about the antifatigue effect of fermented deer blood (FDB) on intense exercise mice. The purpose of the present study is to investigate the antifatigue effect of FDB, and whether this effect is correlated with the altered small intestinal microbiota and metabolites in exercise mice. In this study, 5-week-old male C57BL/6J mice are given treadmill exercise with or without FDB supplementation (30 and 150 mg/kg/d) for 3 weeks. FDB significantly reduces metabolic byproduct accumulation, liver and intestinal damage, and enhances glycogen storage and antioxidant capacity in intense exercise mice. Moreover, FDB restructures the small intestinal microbiota by increasing the abundance of probiotics and butyric acid producing bacteria and decreasing the abundance of pathogenic bacteria. FDB also regulates the levels of metabolites involved in TCA cycle and amino acid metabolism in urine and small intestine content. Correlation analysis shows that FDB-modulated microbiota is highly associated with its antifatigue effect. FDB may ameliorate fatigue and intestinal injury through targeting small intestinal microbiota.

Acupuncture Combined with Chinese Medicine Iontophoresis Treatment for Chronic Progressive Cervical Intervertebral Disk Disease in a Dog.

CASE REPORT: A 12-year-old castrated male dog with nonambulatory tetraplegia was diagnosed with spinal stenosis at C3-C4 through X-ray examination and with ventral extradural spinal compression at C3-C4 through myelography and computed tomography. The diagnosis of traditional Chinese veterinary medicine was local Qi and blood stagnation, spleen Qideficiency, blood deficiency, and kidney Yang deficiency. We initiated treatment using a combination of acupuncture and Chinese medicine iontophoresis with laser therapy. After 12 treatment days, there was a significant improvement in the dog's ambulation function, which was indicated by proper walking and flexible head-turning. CONCLUSION: This indicates that combining acupuncture and Chinese medicine iontophoresis could be a potential treatment for chronic progressive cervical intervertebral disk disease in dogs.

Combination of probiotics with different functions alleviate DSS-induced colitis by regulating intestinal microbiota, IL-10, and barrier function.

The potential of probiotics for treating ulcerative colitis (UC) has attracted increasing attention. However, more studies are still needed to guide physicians on the proper selection and use of probiotics. Here, we propose that combination of multiple probiotics with different functions can reduce intestinal inflammation. In this study, the effects of probiotics (Lactobacillus reuteri, Bacillus coagulans, Bifidobacterium longum, and Clostridium butyricum) on the physiology and histopathology of colon were evaluated in a dextran sulfate sodium (DSS)-induced colitis mouse model. The combined species, as well as the species individually, were tested and compared with sulfasalazine (SASP) and two Chinese herbal therapies. Results show that the functions of the four probiotic strains were different in regulating intestinal immunity and barrier function. The four-species probiotic cocktail was more effective than the species individually and anti-inflammatory drugs in repairing the dysbiosis of mucosal microbial ecology and reducing intestinal inflammation. The multi-strain probiotic mixture increased the proportion of beneficial bacteria and decreased the proportion of pro-inflammatory bacteria in the colonic mucosa. In addition, probiotic mixture significantly enhanced the expression of IL-10 and intestinal barrier function. These results suggest that a combination of multiple probiotics with different functions has synergistic effects and can restore the balance of interactions between microorganisms and immunological niches.

[Acupuncture improves hepatic lipid metabolism by suppressing oxidative stress in obese nonalcoholic fatty liver disease rats].

OBJECTIVE: To investigate the effect of acupuncture of "Daimai"(GB26) on abdominal fat accumulation, lipid metabolism and hepatic oxidative stress in abdominal obese non-alcoholic fatty liver disease (NAFLD) rats. METHODS: male SD rats were divided into 3 groups: normal diet (normal, n＝8), high fat diet control (model) and acupuncture (n＝8/group in the latter 2 groups). The abdominal obese NAFLD model was established by feeding the rats with high fat diet for 12 weeks. EA (2 Hz/15 Hz, 1.5 mA) was applied to bilateral GB26 for 20 min, once every other day for 8 weeks. Rats of the model group were also restrained for 20 min as those in the EA group. The body mass and abdominal circumference were measured weekly, the isolated adipose tissues around the bilateral kidney and epididymis and the fresh liver were weighed. The contents of serum cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), glutamic oxaloacetic aminotransferase (AST) were detected by using an automatic biochemical analyzer. The abdominal visceral fat distribution was acquired by CT scanning. The oxidative stress indexes of the homogenated liver tissues, such as malondialdehyde (MDA) was assayed using sodium thiobarbital (TBA) method, and the activity of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) were assayed by using hydroxylamine method and colorimetric method respectively. The histopathological changes of the liver were observed after staining with hematoxylin-eosin (HE). RESULTS: Following modeling, the body mass and waist circumference, visceral fat weight of bilateral kidneys and testis (visceral fat weight), liver weight, serum ALT, AST, TG and TC and liver MDA contents, were significantly higher in the model group (P<0.001，P<0.05), while hepatic T-SOD and GSH-PX activity was considerably lower in the model group than those in the normal group (P<0.001). After acupuncture intervention, the levels of all the above-mentioned indexes (modeling induced both increase and decrease) were reversed relevant to the model group (P<0.05, P<0.01). The results of CT scanning showed that the fat accumulation area in the abdomen was 8.67 cm2, 18.51 cm2 and 13.75 cm2 in the normal, model and acupuncture groups, respectively, presenting a decrease after acupuncture. H．E. staining displayed that the degree of hepatic steatosis (including vague hepatic lobule boundary, disordered arrangement of hepatic cord, hepatocellular swelling, diffuse fatty degeneration, unequal-sized lipid droplets in the hepatocytes, nucleus excursion and dissolution after modeling) was improved after acupuncture. CONCLUSION: Acupuncture can reduce body weight and abdominal fat accumulation in abdominal obese NAFLD rats, which may be related to its effects in inhibiting oxidative stress (lowering MDA level and increasing the activity of T-SOD and GSH-PX) and improving hepatic lipid metabolism.