Clinical value-oriented research paradigm about inheritance and innovation development of TCM dominant diseases.

Modern medicine has made remarkable achievements in safeguarding people's life and health, however, it is increasingly found that in the face of complex diseases, selective targeting of single target is often difficult to produce a comprehensive rehabilitation effect, and is prone to induce drug resistance, toxic side effects. Traditional Chinese medicine (TCM) has a long history of clinical application, and its clinical value in the treatment of complex diseases such as cardiovascular and cerebrovascular diseases, digestive diseases, skin diseases, rheumatism and immunity diseases, and adjuvant treatment of tumors has been proven to have obvious advantages. However, its modern research is relatively lagging behind, and in the face of the aging society and the characteristics of the modern disease spectrum, the traditional knowledge-driven research paradigm seems to be stuck in a bottleneck and difficult to make greater breakthroughs. Focusing on the key issues of TCM development in the new era, the clinical value-oriented strategy becomes to be a new research paradigm of TCM inheritance and innovation development, and dominant diseases would be the focus of the TCM inheritance and innovation development, which has been highly valued in recent years by the TCM academia and the relevant national management departments. Based on the clinical value, a series of policies are formulated for the selection and evaluation of the TCM dominant diseases (TCMDD), and exploratory researches about the clinical efficacy characteristics, the modern scientific connotation interpretation were carried out. The clinical value-oriented research paradigm of TCMDD inheritance and innovation development has been initially formed, which is characterized by strong policy support as the guarantee, systematic and standardized selection and evaluation methods as the driving force, scientific and effective research on internal mechanisms as the expansion, and effective clinical guidelines and principles as the transformation, which is of great value in promoting the high-quality development of the industries and undertaking of TCM. In this paper, the main policy support, selection and evaluation methods, therapeutic effect characterization, and modern scientific connotation research strategies of TCMDD in recent years have been comprehensively sorted out, with a view to providing the healthy and benign development of the research on TCMDD.

Strategy for economical and enhanced polyhydroxyalkanoate production from synergistic utilization of palm oil and derived wastewater by activated sludge.

The potential of palm oil and derived wastewater pretreated by enzyme as co-substrates to accumulate polyhydroxyalkanoate (PHA) rich in short and medium-chain-length monomers under two feeding strategies was evaluated batchwise through mixed microbial cultures (MMCs) in activated sludge. A terpolymer with the maximum PHA content of 30.5 wt%, volumetric yield of 0.372 g COD/g COD and composition of ca. 84.7 âˆ¼ 97.4/0.5 âˆ¼ 1.6/2.1 âˆ¼ 13.7 (3-hydroxybutyrate/ 3-hydroxyvalerate/ 3-hydroxyoctanoate, %) was achieved as a result of co-substrate incorporation. From the perspective of economic benefits, PHA accumulated via adopting strategy of supplementing carbon source to the same initial concentration per cycle saved 42.7 % of carbon consumption, along with a reduction in culture time (72 h). The above discoveries signify that the combination of palm oil and derived wastewater plus MMCs provides an alternative to the plastics industries for a more sustainable and efficient utilization of biological resources and an economic PHA accumulation approach.

Effects and central mechanism of electroacupuncture and MRI-navigated rTMS for PSD: study protocol for an fMRI-based single-center, randomized, controlled, open-label trial.

Background: Post-stroke depression (PSD) is the most common mental complication after stroke and has a serious impact on functional outcomes and quality of life for stroke patients. Antidepressants are the first-line treatment for PSD; however, many reported side effects remain. Clinical research and practice guidelines have shown that electro-acupuncture (EA) or rTMS have a positive effect on PSD. However, there are few clinical studies on EA and MRI-navigated rTMS for PSD that explore the fMRI-based central mechanism in depression. Methods: In this randomized, controlled, open-label trial, 64 patients with PSD will be randomly allocated into the experiment group (n = 32) or control group (n = 32). The experiment group will receive EA and MRI-navigated rTMS and the control group will receive MRI-navigated rTMS treatment, in 12-20 sessions over 4 weeks. In addition, 10 healthy people for fMRI scanning will be recruited as a healthy control group without any intervention. The primary outcome will be the change from baseline in the Hamilton Depression Scale-24 item (HAMD-24) scores at week 4. The primary analysis of the central mechanism will mainly involve cortical morphology, local spontaneous brain activity, and the default mode network (DMN) functional connectivity based on fMRI at 0 and 4 weeks. Secondary outcomes will include the neuro-patho-physiological and quality of life changes in cortical excitability, determined using the motor evoked potential test (MEP), National Institutes of Health Stroke Scale (NIHSS), EuroQol Five Dimensions Questionnaire (EQ-5D) Scale, Modified Barthel Index (MBI) Scale, and Health Scale of Traditional Chinese Medicine (HSTCM). Additional indicators will include the Acceptability Questionnaire and Health Economics Evaluation (cost-effectiveness analysis) to assess the acceptability and economic practicality of the treatment under study. Outcomes will be assessed at baseline and post intervention. Discussion: EA and MRI-navigated rTMS therapy could become an alternative treatment for PSD, and it is expected that this trial will provide reliable clinical evidence and a potential central mechanism for the future use of EA and MRI-navigated rTMS for PSD. Clinical trial registration: NCT05516680, ClinicalTrials.gov (registered in August 2022).

Deep learning and machine intelligence: New computational modeling techniques for discovery of the combination rules and pharmacodynamic characteristics of Traditional Chinese Medicine.

It has been increasingly accepted that Multi-Ingredient-Based interventions provide advantages over single-target therapy for complex diseases. With the growing development of Traditional Chinese Medicine (TCM) and continually being refined of a holistic view, "multi-target" and "multi-pathway" integration characteristics of which are being accepted. However, its effector substances, efficacy targets, especially the combination rules and mechanisms remain unclear, and more powerful strategies to interpret the synergy are urgently needed. Artificial intelligence (AI) and computer vision lead to a rapidly expanding in many fields, including diagnosis and treatment of TCM. AI technology significantly improves the reliability and accuracy of diagnostics, target screening, and new drug research. While all AI techniques are capable of matching models to biological big data, the specific methods are complex and varied. Retrieves literature by the keywords such as "artificial intelligence", "machine learning", "deep learning", "traditional Chinese medicine" and "Chinese medicine". Search the application of computer algorithms of TCM between 2000 and 2021 in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Elsevier and Springer. This review concentrates on the application of computational in herb quality evaluation, drug target discovery, optimized compatibility and medical diagnoses of TCM. We describe the characteristics of biological data for which different AI techniques are applicable, and discuss some of the best data mining methods and the problems faced by deep learning and machine learning methods applied to Chinese medicine.

Post-stroke treatment of storax improves long-term outcomes of stroke in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The lack of widely applicable pharmacological treatments for ischemic stroke patients has led to a growing interest in traditional medicine. The identification of pharmacologically active components of the clinically used traditional medicine has been considered translationally significant. SuHeXiang Wan is a prescription containing 15 herbs approved by Chinese National Drug Administration (CNDA) for treating ischemic stroke. Storax is one of the main contents in this prescription and is believed to play a significant pharmacological role, which has been used to treat stroke for nearly 1000 years in traditional Chinese medicine. Emerging experimental investigations suggested Storax might be effective for treating ischemic stroke. AIM OF THE STUDY: This study aimed to test our hypothesis that post-stroke treatment of Storax can improve long-term outcomes of stroke. MATERIALS AND METHODS: Male Wistar rats (250-280 g) subjected to 2 h of MCAO following reperfusion were treated with Storax by intragastric at 1 h and repeated at 3 h, 6 h after stroke. In the first set experiment, an array of neurological function deficits assessments were tested before and after stroke, brain lesion size was examined at 28 days after ischemia. CD31 and synatophysin were analyzed by immunohistochemistry. In the second set experiment, markers of proinflammatory activation were determined at 24 h after stroke. ELISA was performed to analyze brain concentrations of TNF-α, IL-1ß and circulating levels of iNOS, ET-1, and immunohistochemistry was performed to determine GFAP, IBA-1 and NF-κB p65. RESULTS: Storax significantly alleviated neurological deficits from 7 days after stroke and lasted until 28 days, corresponding to the significantly decreased lesion volume at 28 days after stroke; Meanwhile, Storax increased the density of CD31and SYP in peri-infarct areas. At 24 h after stroke, Storax significantly inhibited brain TNF-α, IL-1ß expression and circulating iNOS, ET-1 levels, reduced the NF-κB/p65 positive cell number, and decreased activated microglia/macrophages and astrocytes cell numbers alongside reversed their morphological transformations. CONCLUSION: Our experimental findings demonstrate treatment of Storax at the acute phase significantly improves long-term neurological outcomes in the focal stroke model of rats. We also speculate that inhibition of acute proinflammation activation by Storax might be associated with its beneficial pharmacological effect, but remain to define and elucidate in future investigation.

Duzhong Fang Attenuates the POMC-Derived Neuroinflammation in Parkinsonian Mice.

BACKGROUND: Neuroinflammation and microglia reactivity are now recognized to be features of Parkinson's disease (PD). Thus, microglia phenotype is a potential new target for developing treatments against PD. Duzhong Fang (DZF) is a traditional Chinese medicine (TCM) prescription. The theory of TCM argues that Duzhong Fang, nourishing yin and tonifying yang, may treat PD. However, its modern pharmacological studies and the underlying mechanisms are unclear. METHODS: First, MPTP was used to establish a parkinsonian mouse model, and behavioral testing was used to evaluate the locomotor dysfunction. Then, HPLC, immunohistochemical staining, and Western blot assays were performed to evaluate the survival of dopaminergic neurons. Molecular biological and immunofluorescence staining were used to evaluate the neuroinflammation and microglial activation. In addition, RNA-seq transcriptomics was used to analyze differentially expressed genes and verify by RT-PCR. RESULTS: In the present study, we first confirmed that DZF can alleviate neuroinflammation and ameliorate dyskinesia in parkinsonian mice. Then, further studies found that DZF can regulate microglial morphology and reactivity and act on the POMC gene. POMC is an upstream target for regulating inflammation and proinflammatory cytokines, and DZF can directly inhibit the POMC level and restore the homeostatic signature of microglia in parkinsonian mice. CONCLUSION: This study found that POMC may have a potential role as a therapeutic target for PD. DZF may inhibit neuroinflammation and play an anti-PD effect by down-regulating the expression of POMC.

Anti-neuroinflammatory effects of Eucommia ulmoides Oliv. In a Parkinson's mouse model through the regulation of p38/JNK-Fosl2 gene expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv., a Chinese medicinal herb called "Duzhong" from the bark of Eucommia ulmoides Oliv., has been shown to possess significant protective effects in Parkinson's disease (PD). However, the molecular mechanism remains unclear. AIM OF THE STUDY: In this study, we explored the anti-neuroinflammatory mechanisms of Duzhong on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model to elucidate the traditional medical theories with modern pharmacological methods and to provide a reference for further clarifying its mechanisms of action. MATERIALS AND METHODS: The representative components in Duzhong extract were identified by UPLC-Q-TOF/MS. Male C57BL/6J mice were intraperitoneally injected with MPTP to establish an in vivo PD model. The pole, rotarod, and grip strength tests were performed to evaluate the motor coordination ability of the PD mice. HPLC-ECD was used to detect the striatal levels of dopamine (DA), 3,4- dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The expression of tyrosine hydroxylase (TH) was studied by immunohistochemistry (IHC) and Western blot assays. ELISA and Q-PCR were used examined the levels of proinflammatory cytokines in the serum and midbrain, respectively. Whole-transcriptome analysis of the midbrain was performed to explore the therapeutic effect of Duzhong on PD mice, and Q-PCR was then used to validate the differential gene expression changes in the PD mice treated with Duzhong. RESULTS: Ten compounds were identified from Duzhong extract. Duzhong significantly alleviated the behavioral impairments and dopaminergic neuron degeneration of PD mice, and inhibited the expression of proinflammatory cytokines. Whole-transcriptome analysis revealed nine oppositely regulated genes, and the Fosl2 gene was consistent with the trend of observed by RNA-seq. Furthermore, Duzhong downregulated mRNA expression of p38 and JNK, which are key upstream genes of Fosl2. CONCLUSIONS: Duzhong has promising therapeutic potential in PD mice, and its molecular mechanism is mediated by downregulating p38/JNK-Fosl2 gene expression to alleviate neuroinflammation.

Aqueous extracts of Tribulus terrestris protects against oxidized low-density lipoprotein-induced endothelial dysfunction.

OBJECTIVE: To investigate the role of aqueous extracts of Tribulus terrestris (TT) against oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) dysfunction in vitro. METHODS: HUVECs were pre-incubated for 60 min with TT (30 and 3 µg/mL respectively) or 10(-5) mol/L valsartan (as positive controls) and then the injured endothelium model was established by applying 100 µg/mL ox-LDL for 24 h. Cell viability of HUVECs was observed by real-time cell electronic sensing assay and apoptosis rate by Annexin V/PI staining. The cell migration assay was performed with a transwell insert system. Cytoskeleton remodeling was observed by immunofluorescence assay. The content of endothelial nitric oxide synthase (eNOS) was measured by enzyme-linked immunosorbent assay. Intracellular reactive oxygen species (ROS) generation was assessed by immunofluorescence and flow cytometer. Key genes associated with the metabolism of ox-LDL were chosen for quantitative real-time polymerase chain reaction to explore the possible mechanism of TT against oxidized LDL-induced endothelial dysfunction. RESULTS: TT suppressed ox-LDL-induced HUVEC proliferation and apoptosis rates significantly (41.1% and 43.5% after treatment for 3 and 38 h, respectively; P<0.05). It also prolonged the HUVEC survival time and postponed the cell's decaying stage (from the 69th h to over 100 h). According to the immunofluorescence and transwell insert system assay, TT improved the endothelial cytoskeletal network, and vinculin expression and increased cell migration. Additionally, TT regulated of the synthesis of endothelial nitric oxide synthase and generation of intracellular reactive oxygen species (P<0.05). Both 30 and 3 µg/mL TT demonstrated similar efficacy to valsartan. TT normalized the increased mRNA expression of PI3Kα and Socs3. It also decreased mRNA expression of Akt1, AMPKα1, JAK2, LepR and STAT3 induced by ox-LDL. The most notable changes were JAK2, LepR, PI3Kα, Socs3 and STAT3. CONCLUSIONS: TT demonstrated potential lowering lipid benefits, anti-hypertension and endothelial protective effects. It also suggested that the JAK2/STAT3 and/or PI3K/AKT pathway might be a very important pathway which was involved in the pharmacological mechanism of TT as the vascular protective agent.

Effect of copper on the expression of TGF-ß in incubated chondrocytes of newborn pigs.

This experiment was conducted to measure the effect of copper supplementation on TGF-ß gene expression in chondrocytes of newborn pigs. Chondrocytes were cultured in media containing 15% fetal calf serum supplemented with 0, 15.6, 31.2, and 62.5 µmol/L copper in 90-mm culture plate. Total RNA was isolated from chondrocytes, and TGF-ß cDNA was synthesized, amplified, and sequenced. The expression level of TGF-ß was examined by reverse transcription polymerase chain reaction. The results showed that the sequence of the cloned TGF-ß gene was 99.4% identical to that in GenBank. The expression of TGF-ß increased in culture media added with final concentration of 15.6, 31.2, and 62.5 µmol/L copper. In this study, the optimal copper concentration and optimal culture time for the highest level of TGF-ß expression were 31.2 µmol/L and 48 h, respectively.