Therapeutic effects of high-dose vitamin C supplementation in patients with COVID-19: a meta-analysis.

CONTEXT: Coronavirus disease 2019 (COVID-19) could induce the "cytokine storm" due to overactivation of immune system and accompanied by acute respiratory distress syndrome as a serious complication. Vitamin C has been effective in improving lung function of patients by reducing inflammation. OBJECTIVE: The aim was to explore the therapeutic effects of high-dose vitamin C supplementation for patients with COVID-19 using meta-analysis. DATA SOURCES: Published studies were searched from PubMed, Cochrane Library, Web of Science, EMBASE, and China National Knowledge Infrastructure databases up to August 2022 using the terms "vitamin C" and "COVID-19". Data analyses were performed independently by 2 researchers using the PRISMA guidelines. DATA EXTRACTION: Heterogeneity between the included studies was assessed using I2 statistics. When I2 ≥50%, the random-effects model was used; otherwise, a fixed-effects model was applied. Stata 14.0 software was used to pool data by standardized mean differences (SMDs) with 95% CIs or odds ratios (ORs) with 95% CIs. DATA ANALYSIS: The 14 studies had a total of 751 patients and 1583 control participants in 7 randomized controlled trials and 7 retrospective studies. The vitamin C supplement significantly increased ferritin (SMD = 0.272; 95% CI: 0.059 to 0.485; P = 0.012) and lymphocyte count levels (SMD = 0.376; 95% CI: 0.153 to 0.599; P = 0.001) in patients with COVID-19. Patients administered vitamin C in the length of intensive care unit staying (SMD = 0.226; 95% CI: 0.073 to 0.379; P = 0.004). Intake of vitamin C prominently alleviate disease aggravation (OR = 0.344, 95%CI: 0.135 to 0.873, P = 0.025). CONCLUSIONS: High-dose vitamin C supplementation can alleviate inflammatory response and hinder the aggravation of COVID-19.

[Water Quality Change Trend and Risk Analysis of Wuhan Hanjiang River Water Source].

Hanjiang River is closely related to the middle route of the South-to-North Water Diversion Project, the Water Diversion Project from the Hanjiang River to the Wei River, and the Water Diversion Project in Northern Hubei. The Wuhan Hanjiang River water source is one of the important drinking water sources in China; its water quality safety is significant to living and production for millions of residents in Wuhan. Based on data from 2004 to 2021, the water quality variation trend and risk of Wuhan Hanjiang River water source were studied. The results showed that a certain gap existed between the concentrations of some pollutants such as total phosphorus, permanganate index, ammonia nitrogen, and correspondent water quality target, especially for the total phosphorus. The growth of algae in the water source was marginally limited by the concentrations of nitrogen, phosphorus, and silicon. When other factors remained unchanged, diatoms tended to grow rapidly when the water temperature was appropriate (6-12℃). The quality of water upstream had a great impact on the water quality of the Hanjiang water source. There may have been pollutants entering into the reach during the West Lake Water Plant and Zongguan Water Plant. There were differences in the temporal and spatial variation trend of concentrations between permanganate index, total nitrogen, total phosphorus, and ammonia nitrogen. Significant changes in the ratio of nitrogen and phosphorus in the water body will affect the population structure and quantity of planktonic algae and ultimately affect the safety of water quality. The water body in the water source area was generally in the state of medium nutrition to mild eutrophication, and middle eutrophication may have occurred in a few periods. In recent years, the nutritional level of the water source has been on the decline. It is necessary to make an in-depth investigation on the source, quantity, and change trend of pollutants in water sources in order to eliminate potential risks.

Ligand fishing of monoamine oxidase B inhibitors from Platycodon grandiflorus (Jacq.) A.DC. roots by the enzyme functionalised magnetic nanoparticles.

INTRODUCTION: As a famous traditional Chinese medicine, roots of Platycodon grandiflorus (Jacq.) A.DC. have shown multiple effects against neurodegenerative diseases. To investigate the components against Parkinson's disease (PD), the roots of P. grandiflora were selected as the research subject. OBJECTIVE: Screening and identifying of monoamine oxidase B (MAO-B) inhibitors from the roots of P. grandiflorum via enzyme functionalised magnetic nanoparticles (MNPs)-based ligand fishing combined with high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. METHOD: MAO-B functionalised MNPs have been synthesised for screening MAO-B inhibitors from the roots of P. grandiflorum. The ligands were identified by HPLC-MS and nuclear magnetic resonance (NMR) analysis, and their anti-PD activity was evaluated via MAO-B inhibition assay and cell viability assay in vitro. RESULTS: Two MAO-B inhibitors were fished out and identified by HPLC-MS as protocatechuic aldehyde (1) and coumarin (2), with the half maximal inhibitory concentrations of 28.54 ± 0.39 and 25.39 ± 0.29 µM, respectively. Among them, 1 could also significantly increase the viability of 6-hydroxydopamine-damaged PC12 cells. CONCLUSION: The results are helpful to elucidate the anti-PD activity of the plant, and the ligand fishing method has shown good potential in discovery of MAO-B inhibitors.

Neuroprotective Effects of Lycium Barbarum Fruit Extract on Pink1B9Drosophila Melanogaster Genetic Model of Parkinson's Disease.

Lycium barbarum (LB) is a famous traditional Chinese medicinal plant as well as food supplement possessing various pharmacological functions such as anti-aging and antioxidant effects. The Parkinson's disease (PD)-related kinase Pink1 plays vital role in maintaining the neuron cell homeostasis, having been recognized as a potential target for the development of anti-PD drugs. In this work, the neuroprotective effects of methanol extract of LB fruit (LBFE) were investigated using a Drosophila PD model (PINK1B9) and a human neuroblastoma SH-SY5Y cell line. We found that when LBFE was supplied to the PINK1B9 flies at 6, 12, and 18 days of age, it raised the ATP and dopamine levels at all ages, extended life span, improved motor behavior, and rescued olfactory deficits of the PINK1B9 flies. In addition, histopathological examinations indicated that muscle atrophy in thoraces of the mutant flies was significantly repaired. Finally, LBFE was able to rescue the SH-SY5Y cells against MPP+-induced neurotoxicity. This work reports for the first time the anti-PD potential of L. barbarum fruit extract in PINK1 mutant fruit flies, presenting a new viewpoint for studing the mechanism of action of LBFE.

The impact of acupuncture on neuroplasticity after ischemic stroke: a literature review and perspectives.

Ischemic stroke is common in the elderly, and is one of the main causes of long-term disability worldwide. After ischemic stroke, spontaneous recovery and functional reconstruction take place. These processes are possible thanks to neuroplasticity, which involves neurogenesis, synaptogenesis, and angiogenesis. However, the repair of ischemic damage is not complete, and neurological deficits develop eventually. The WHO recommends acupuncture as an alternative and complementary method for the treatment of stroke. Moreover, clinical and experimental evidence has documented the potential of acupuncture to ameliorate ischemic stroke-induced neurological deficits, particularly sequelae such as dyskinesia, spasticity, cognitive impairment, and dysphagia. These effects are related to the ability of acupuncture to promote spontaneous neuroplasticity after ischemic stroke. Specifically, acupuncture can stimulate neurogenesis, activate axonal regeneration and sprouting, and improve the structure and function of synapses. These processes modify the neural network and function of the damaged brain area, producing the improvement of various skills and adaptability. Astrocytes and microglia may be involved in the regulation of neuroplasticity by acupuncture, such as by the production and release of a variety of neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Moreover, the evidence presented indicates that acupuncture promotes neuroplasticity by modulating the functional reconstruction of the whole brain after ischemia. Therefore, the promotion of neuroplasticity is expected to become a new target for acupuncture in the treatment of neurological deficits after ischemic stroke, and research into the mechanisms responsible for these actions will be of significant clinical value.

Upregulation of N-Type Voltage-Gated Calcium Channels Induces Neuropathic Pain in Experimental Autoimmune Neuritis.

Objective: Guillain-Barré syndrome (GBS) is a common autoimmune disease of the peripheral nervous system, and there is still no effective treatment for GBS. This investigation intends to figure out the effect and mechanism of N-type voltage-gated calcium (Cav2.2) channels on neuropathic pain in GBS. Methods: An experimental autoimmune neuritis (EAN) model was established in Lewis rats induced by myelin P253-78 peptide and complete Freund's adjuvant. Luxol fast blue (LFB) staining was used for observing the degree of cell infiltration and demyelination in the sciatic nerve of rats, ELISA for detecting IL-6 and TNF-α expression in the serum, qRT-PCR, and Western blot for measuring the expression of iNOS, MCP-1, and Cav2.2 in the sciatic nerve, respectively. Results: EAN led to significant decreases in the mechanical withdrawal threshold, thermal withdrawal threshold, and mechanical hyperalgesia threshold and an increase in the withdrawal threshold to cold stimulation. The serum IL-6 and TNF-α expression was significantly increased, and the mRNA and protein expression of iNOS, MCP-1, and Cav2.2 in the sciatic nerve were significantly increased in the EAN rats. However, silencing Cav2.2 expression could significantly reverse the above EAN-caused results. Conclusion: Silencing Cav2.2 expression can significantly reduce the clinical score, pathological injury, and mechanical allodynia, reducing the release of inflammatory factors, thus improving neuropathic pain in EAN rats.

[New method for green extraction of ginsenosides based on mechanochemically-assisted extraction and deep eutectic solvents].

Ginsenosides are the main active ingredients in ginseng. Studies have shown that ginsenosides have anti-virus, anti-tumor, anti-aging, nootropic, cardiovascular diseases-protecting, and other pharmacological activities. Thus, the development and utilization of ginsenosides have persistently attracted much attention. At present, the extraction of ginsenosides is mainly based on organic solvents, and there are relatively few studies on their green extraction. In this study, different deep eutectic solvents(DESs) were synthesized by heating and stirring method, combined with an emerging technology, mechanochemically-assisted extraction(MCAE), to extract ginsenosides in a green way. Six parameters that might affect the extraction effect were optimized to determine the optimal conditions, and the method validation was conducted. The new established method was compared with a commonly used extraction method(ultrasound-assisted extraction using 70% ethanol) to evaluate its extraction efficiency. The results revealed that the optimal extraction conditions of DES-MCAE were that the volume ratio of DES3(choline chloride∶urea 1∶2) and water in the extraction solvent was 6∶4, and the liquid ratio and the linear vibration speed were 0.05 g·mL~(-1) and 4.0 m·s~(-1); the extraction was performed twice, 40 s each. With only 80 s extraction, the extraction rate of this method was 36.22% higher than that of ultrasoun-dassisted extraction using 70% ethanol. In this study, a DESs-based pretreatment method for ginsenosides was established and its rapid, green and efficient extraction was realized, which provided new ideas and methods for further research on green extraction of other active ingredients from Chinese medicine.

The anti-neoplastic activities of aloperine in HeLa cervical cancer cells are associated with inhibition of the IL-6-JAK1-STAT3 feedback loop.

Cervical cancer (CC) is recognized as the most common neoplasm in the female reproductive system worldwide. The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients. Aloperine (ALO) is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation, allergies and infection. However, its therapeutic efficacy and underlying mechanism in CC are still unclear. In the current study, MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC. Then, the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry, respectively, while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay. Moreover, nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo. The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis. This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest. Simultaneously, ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio. Additionally, the migration and invasion of HeLa cells were attenuated by ALO treatment, which was considered to result from inhibition of epithelial-to-mesenchymal transition. For molecular mechanisms, the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment. This study indicated that ALO markedly suppresses the proliferation, migration and invasion and enhances the apoptosis of HeLa cells. In addition, these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.

A systematic approach to decode the mechanism of Cornus in the treatment of hepatocellular carcinoma (HCC).

Cornus Officinalis (Cornus), the dried pulp of mature Cornus, is used to treat liver diseases. However, the pharmacological mechanism of Cornus in the treatment of hepatocellular carcinoma (HCC) has not been systematically studied. The chemical compounds and the bioactive chemical compounds of Cornus were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Cards database was used to explore the targets in liver cancer pathogenesis. The disease-drug Venn diagram was constructed using the VENN 2.1 and the STRING database was used to analyze protein-protein Interaction Network (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using the R package. Molecular docking was performed using Discovery Studio were assessed using Pymol and Discovery Studio 2016. Cell survival of BEL-7404 cells treated by Hydroxygenkwanin (HGK) were valued through CCK-8 assay. Expressions of caspase-3 and cleaved PARP was detected through Western blot. Pharmacological network diagrams of the Cornus compound-target network and HCC-related target network were successfully constructed. A total of 20 active compounds, 1841 predicted biological targets of Cornus, and 7100 HCC-related targets were identified. 37 target genes between Cornus and HCC were screened trough the network pharmacology. Molecular docking studies suggested that HGK has the highest affinity with caspase-3. HGK could induce apoptosis of HCC cells and significantly activate the caspase-3 protease activity in BEL-7404. This study systematically elaborated the mechanism of Cornus in the treatment of HCC and provided a new perspective to exploit Antineoplastic from Cornus.

Effect of Chinese Herbal Medicines on Hearing Loss Risk in Rheumatoid Arthritis Patients: Retrospective Claims Analysis.

Objectives: Patients with rheumatoid arthritis (RA) are at a higher risk of extra-articular manifestations, especially hearing loss (HL). Although Chinese herbal medicines (CHM) are proven safe and effective treatments for inflammatory conditions, the effect of CHM use on HL in RA patients is unknown. This cohort study aims to determine the relationship between CHM use and the subsequent risk of HL among RA patients. Methods: From health insurance claims data in Taiwan, a total of 6,905 persons aged 20-80 years with newly-diagnosed RA in 2000-2009 were identified. Of these, we recruited 2,765 CHM users and randomly selected 2,765 non-CHM users who matched with the users by the propensity score. Both cohorts were followed up until the end of 2012 to estimate the incidence of HL. Cox proportional hazards regression was used to estimate the adjusted hazard ratio (HR) for HL. Results: The incidence of HL was lower in the CHM users than in the comparison cohort (8.06 vs. 10.54 per 1,000 person-years) (adjusted HR, 0.77; 95% CI, 0.63-0.94). Those who received CHM for more than 2 years had the greatest benefit against the onset of HL, with over 50% risk reduction. Prescriptions of Hai Piao Xiao, Yan Hu Suo, San-Qi, Huang Qin, Dang Shen, Jia-Wei-Xiao-Yao-San, Shu-Jing-Huo-Xue-Tang, and Dang-Gui-Nian-Tong-Tang were found to be associated with a reduced risk of HL. Conclusions: Our findings suggest that adding CHM to conventional therapy may reduce the subsequent risk of HL in RA patients. Prospective randomized trials are recommended to further clarify whether the association revealed in this study supports such a causal relationship.

Role of Neuroimmune Crosstalk in Mediating the Anti-inflammatory and Analgesic Effects of Acupuncture on Inflammatory Pain.

Inflammatory pain is caused by peripheral tissue injury and inflammation. Inflammation leads to peripheral sensitization, which may further cause central sensitization, resulting in chronic pain and progressive functional disability. Neuroimmune crosstalk plays an essential role in the development and maintenance of inflammatory pain. Studies in recent years have shown that acupuncture can exert anti-inflammatory and analgesic effects by regulating peripheral (i.e., involving local acupoints and inflamed regions) and central neuroimmune interactions. At the local acupoints, acupuncture can activate the TRPV1 and TRPV2 channels of mast cells, thereby promoting degranulation and the release of histamine, adenosine, and other immune mediators, which interact with receptors on nerve endings and initiate neuroimmune regulation. At sites of inflammation, acupuncture enables the recruitment of immune cells, causing the release of opioid peptides, while also exerting direct analgesic effects via nerve endings. Furthermore, acupuncture promotes the balance of immune cells and regulates the release of inflammatory factors, thereby reducing the stimulation of nociceptive receptors in peripheral organs. Acupuncture also alleviates peripheral neurogenic inflammation by inhibiting the release of substance P (SP) and calcitonin gene-related peptide from the dorsal root ganglia. At the central nervous system level, acupuncture inhibits the crosstalk between glial cells and neurons by inhibiting the p38 MAPK, ERK, and JNK signaling pathways and regulating the release of inflammatory mediators. It also reduces the excitability of the pain pathway by reducing the release of excitatory neurotransmitters and promoting the release of inhibitory neurotransmitters from neurons and glial cells. In conclusion, the regulation of neuroimmune crosstalk at the peripheral and central levels mediates the anti-inflammatory and analgesic effects of acupuncture on inflammatory pain in an integrated manner. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of inflammatory diseases.

[Research progress on culture technologies,chemical components,and pharmacological activities of Saussurea involucrata cells].

Saussurea involucrata,a traditional Chinese medicinal material,is effective in the treatment of rheumatoid arthritis with cold-dampness blockage syndrome,cold pain in lower abdomen,and menstrual irregularities. However,due to the specific habitat,low natural reproduction rate,slow growth,and overexploitation,it is at the high risk of extinction. S. involucrata cells can be obtained through callus culture,suspension culture,and hairy root culture. This study highlighted the influences of reactor type,culture system,precursor,elicitor type, and light wavelength on the suspension culture of S. involucrate cells. The chemical components of S. involucrata cells mainly include phenylpropanoids,flavonoids,lignans,and steroids,among which phenylpropanoids are the most abundant. S. involucrata cells have multiple pharmacological activities of anti-inflammation,analgesia,activating blood and resolving stasis,immunoregulation,increasing bone density,lowering blood lipids,anti-hypoxia,anti-exercise fatigue,anti-radiation,anti-obesity,and anti-oxidation. Moreover,it has the potential of treating aplastic anemia. This study reviews the cell culture technologies,chemical components,and pharmacological activities of S. involucrata cells,laying a basis for the further research,development,and utilization.

Molecular insight into the variation of dissolved organic phosphorus in a wastewater treatment plant.

To date, eutrophication becomes a great concern of vulnerable aquatic systems. Dissolved organic phosphorus (DOP) discharged from wastewater treatment plant (WWTP) holds a large source of phosphorus in receiving water. However, due to the complexity of DOP, their variation and fate in WWTP remain unknown at the molecular level, and are always overlooked. Here, the variation of DOP in a WWTP was uncovered via Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). Results show that 95% of DOP in the influent could be removed by the secondary biological treatment processes. The removed DOP species were mainly lipids with the molecular characteristics of low oxygen content, low unsaturation and low aromaticity. Meanwhile, during biological treatments, some new DOP species, especially lignin/carboxylic rich alicyclic molecules (CRAM) that possessed high oxygen content, high unsaturation and high aromaticity, were produced and released into the secondary effluent. In the subsequent tertiary treatment, coagulation by aluminum salt tended to remove high molecular weight and high oxygen content DOP species in the secondary effluent, which was complementary to the biological treatment. However, the sand filter usually retained microorganisms, which would result in the generation of new DOP species in this process. During the final ultraviolet disinfection process, DOP was effectively mineralized to phosphate, especially the species with high molecular weight and highly unsaturated aromatic DOP species (e.g., lignin/CRAM and tannin), which had higher UV absorbance. The revealed variation of DOP in WWTP is beneficial to optimize the treatment processes to enhance the removal of DOP.

Acupuncture for Parkinson's Disease: Efficacy Evaluation and Mechanisms in the Dopaminergic Neural Circuit.

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disease caused by degeneration of dopaminergic neurons in the substantia nigra. Existing pharmaceutical treatments offer alleviation of symptoms but cannot delay disease progression and are often associated with significant side effects. Clinical studies have demonstrated that acupuncture may be beneficial for PD treatment, particularly in terms of ameliorating PD symptoms when combined with anti-PD medication, reducing the required dose of medication and associated side effects. During early stages of PD, acupuncture may even be used to replace medication. It has also been found that acupuncture can protect dopaminergic neurons from degeneration via antioxidative stress, anti-inflammatory, and antiapoptotic pathways as well as modulating the neurotransmitter balance in the basal ganglia circuit. Here, we review current studies and reflect on the potential of acupuncture as a novel and effective treatment strategy for PD. We found that particularly during the early stages, acupuncture may reduce neurodegeneration of dopaminergic neurons and regulate the balance of the dopaminergic circuit, thus delaying the progression of the disease. The benefits of acupuncture will need to be further verified through basic and clinical studies.

The role of macrophage polarization and associated mechanisms in regulating the anti-inflammatory action of acupuncture: a literature review and perspectives.

Acupuncture is used in the treatment of a variety of inflammatory conditions and diseases. However, the mechanisms of its anti-inflammatory action are complex and have not been systematically investigated. Macrophages are key components of the innate immune system, thus, balancing the M1/M2 macrophage ratio and modulating cytokine levels in the inflammatory environment may be desirable therapeutic goals. Evidence has shown that acupuncture has anti-inflammatory actions that affect multiple body systems, including the immune, locomotory, endocrine, nervous, digestive, and respiratory systems, by downregulating pro-inflammatory M1 and upregulating anti-inflammatory M2 macrophages, as well as by modulating associated cytokine secretion. Macrophage polarization is controlled by the interlocking pathways of extrinsic factors, the local tissue microenvironment, and the neural-endocrine-immune systems. It has been suggested that polarization of T lymphocytes and cytokine secretions resulting in modulation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, may be upstream mechanisms of acupuncture-induced macrophage polarization. We further propose that macrophage polarization could be the principal pathway involved in acupuncture immune regulation and provide the scientific basis for the clinical application of acupuncture in inflammatory conditions.

The Role of Neuroglial Crosstalk and Synaptic Plasticity-Mediated Central Sensitization in Acupuncture Analgesia.

Although pain is regarded as a global public health priority, analgesic therapy remains a significant challenge. Pain is a hypersensitivity state caused by peripheral and central sensitization, with the latter considered the culprit for chronic pain. This study summarizes the pathogenesis of central sensitization from the perspective of neuroglial crosstalk and synaptic plasticity and underlines the related analgesic mechanisms of acupuncture. Central sensitization is modulated by the neurotransmitters and neuropeptides involved in the ascending excitatory pathway and the descending pain modulatory system. Acupuncture analgesia is associated with downregulating glutamate in the ascending excitatory pathway and upregulating opioids, 𝛾-aminobutyric acid, norepinephrine, and 5-hydroxytryptamine in the descending pain modulatory system. Furthermore, it is increasingly appreciated that neurotransmitters, cytokines, and chemokines are implicated in neuroglial crosstalk and associated plasticity, thus contributing to central sensitization. Acupuncture produces its analgesic action by inhibiting cytokines, such as interleukin-1ß, interleukin-6, and tumor necrosis factor-α, and upregulating interleukin-10, as well as modulating chemokines and their receptors such as CX3CL1/CX3CR1, CXCL12/CXCR4, CCL2/CCR2, and CXCL1/CXCR2. These factors are regulated by acupuncture through the activation of multiple signaling pathways, including mitogen-activated protein kinase signaling (e.g., the p38, extracellular signal-regulated kinases, and c-Jun-N-terminal kinase pathways), which contribute to the activation of nociceptive neurons. However, the responses of chemokines to acupuncture vary among the types of pain models, acupuncture methods, and stimulation parameters. Thus, the exact mechanisms require future clarification. Taken together, inhibition of central sensitization modulated by neuroglial plasticity is central in acupuncture analgesia, providing a novel insight for the clinical application of acupuncture analgesia.

The Anti-Inflammatory Actions and Mechanisms of Acupuncture from Acupoint to Target Organs via Neuro-Immune Regulation.

Inflammation plays a significant role in the occurrence and development of multiple diseases. This study comprehensively reviews and presents literature from the last five years, showing that acupuncture indeed exerts strong anti-inflammatory effects in multiple biological systems, namely, the immune, digestive, respiratory, nervous, locomotory, circulatory, endocrine, and genitourinary systems. It is well known that localized acupuncture-mediated anti-inflammatory effects involve the regulation of multiple populations and functions of immune cells, including macrophages, granulocytes, mast cells, and T cells. In acupuncture stimulation, macrophages transform from the M1 to the M2 phenotype and the negative TLR4 regulator PPARγ is activated to inhibit the intracellular TLR/MyD88 and NOD signaling pathways. The downstream IκBα/NF-κB and P38 MAPK pathways are subsequently inhibited by acupuncture, followed by suppressed production of inflammasome and proinflammatory mediators. Acupuncture also modulates the balance of helper T cell populations. Furthermore, it inhibits oxidative stress by enhancing SOD activity via the Nrf2/HO-1 pathway and eliminates the generation of oxygen free radicals, thereby preventing inflammatory cell infiltration. The anti-inflammatory effects of acupuncture on different biological systems are also specific to individual organ microenvironments. As part of its anti-inflammatory action, acupuncture deforms connective tissue and upregulates the secretion of various molecules in acupoints, further activating the NF-κB, MAPK, and ERK pathways in mast cells, fibroblasts, keratinocytes, and monocytes/macrophages. The somatic afferents present in acupuncture-activated acupoints also convey sensory signals to the spinal cord, brainstem, and hypothalamic neurons. Upon information integration in the brain, acupuncture further stimulates multiple neuro-immune pathways, including the cholinergic anti-inflammatory, vagus-adrenal medulla-dopamine, and sympathetic pathways, as well as the hypothalamus-pituitary-adrenal axis, ultimately acting immune cells via the release of crucial neurotransmitters and hormones. This review provides a scientific and reliable basis and viewpoints for the clinical application of acupuncture in various inflammatory conditions.

Effects and Mechanisms of Acupuncture Combined with Mesenchymal Stem Cell Transplantation on Neural Recovery after Spinal Cord Injury: Progress and Prospects.

Spinal cord injury (SCI) is a structural event with devastating consequences worldwide. Due to the limited intrinsic regenerative capacity of the spinal cord in adults, the neural restoration after SCI is difficult. Acupuncture is effective for SCI-induced neurologic deficits, and the potential mechanisms responsible for its effects involve neural protection by the inhibition of inflammation, oxidation, and apoptosis. Moreover, acupuncture promotes neural regeneration and axon sprouting by activating multiple cellular signal transduction pathways, such as the Wnt, Notch, and Rho/Rho kinase (ROCK) pathways. Several studies have demonstrated that the efficacy of combining acupuncture with mesenchymal stem cells (MSCs) transplantation is superior to either procedure alone. The advantage of the combined treatment is dependent on the ability of acupuncture to enhance the survival of MSCs, promote their differentiation into neurons, and facilitate targeted migration of MSCs to the spinal cord. Additionally, the differentiation of MSCs into neurons overcomes the problem of the shortage of endogenous neural stem cells (NSCs) in the acupuncture-treated SCI patients. Therefore, the combination of acupuncture and MSCs transplantation could become a novel and effective strategy for the treatment of SCI. Such a possibility needs to be verified by basic and clinical research.

Adenine-Functionalized Supramolecular Micelles for Selective Cancer Chemotherapy.

Functional supramolecular micelles containing self-complementary multiple hydrogen bonding adenine groups (A-PPG) can spontaneously self-assemble into stable nanosized micelles in aqueous solution. These micelles can be used to selectively deliver anticancer drugs to cancer cells and effectively promote tumor cell death via apoptosis, without harming normal cells. The drug-loaded micelles exhibit tunable drug-loading capacity and rapid pH-triggered drug release under acidic conditions, as well as a high drug-entrapment stability in serum-rich media due to the reversible hydrogen-bonded adenine-adenine interactions within the micellar interior; these properties are critical to achieving effective chemotherapeutic drug delivery and controlled drug release. In vitro assays show that the drug-loaded micelles exert significant cytotoxic effects on cancer cells, with minimal effects on normal cells under physiological conditions. Cytotoxicity assays using A-PPG micelles loaded with different anticancer drugs confirm these effects. Importantly, cellular internalization and flow cytometric analyses demonstrate that the adenine moieties within A-PPG micelles significantly increase selective endocytic uptake of the supramolecular micelles by cancer cells, which in turn induce apoptotic cell death and substantially enhance the response to chemotherapy. Thus, A-PPG micelles can improve the safety and efficacy of cancer chemotherapy.

Efficacy and Safety of Bushenjiangya-Optimized Granule for Left Ventricular Diastolic Dysfunction in Hypertensive Patients: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: The study aimed to evaluate the efficacy and safety of Bushenjiangya-optimized (BSJYO) granule on left ventricular diastolic dysfunction (LVDD) in hypertensive (HTN) patients. METHODS: 120 patients diagnosed with HTN plus LVDD were randomly assigned to the BSJYO granule group and placebo group, and all patients received basal western medicine (WM) treatment. After eight weeks of treatment, we evaluated echocardiography, traditional Chinese medicine (TCM) syndromes, 24-hour ambulatory blood pressure, liver and kidney functions, and adverse events. Major adverse cardiovascular events (MACEs) were collected at 6-month follow-up. RESULTS: Compared with pretreatment, E/Ea (Doppler-derived index of filling pressure and worsening LVDD) significantly decreased significantly after 8 weeks of treatment in the BSJYO granule plus basal WM group (10.52 ± 1.87 vs. 9.49 ± 1.49, P < 0.01), alongside reductions in significantly effective response (SER), effective response (ER), and total effective response (TER = SER + ER) in TCM symptom scores (21.59% vs. 71.70%, P < 0.01). There were no differences between treatment groups in kidney and liver function, early adverse events, or MACE. CONCLUSION: BSJYO granule plus basal WM is an effective and safe therapy for HTN patients with LVDD.