Traditional Tibetan medicine: therapeutic potential in lung diseases.

Lung diseases have become a major threat to human health worldwide. Despite advances in treatment and intervention in recent years, effective drugs are still lacking for many lung diseases. As a traditional natural medicine, Tibetan medicine has had a long history of medicinal use in ethnic minority areas, and from ancient times to the present, it has a good effect on the treatment of lung diseases and has attracted more and more attention. In this review, a total of 586 Tibetan medicines were compiled through literature research of 25 classical works on Tibetan medicine, drug standards, and some Chinese and English databases. Among them, 33 Tibetan medicines have been studied to show their effectiveness in treating lung diseases. To investigate the uses of these Tibetan medicines in greater depth, we have reviewed the ethnomedicinal, phytochemical and pharmacological properties of the four commonly used Tibetan medicines for lung diseases (rhodiola, gentian, sea buckthorn, liexiang dujuan) and the five most frequently used Tibetan medicines (safflower, licorice, sandalwood, costus, myrobalan). It is expected to provide some reference for the development of new drugs of lung diseases in the future.

[Clinical study of electroacupuncture therapy on postoperative rehabilitation of patients with knee fractures].

OBJECTIVE: To investigate the effect of electroacupuncture therapy on postoperative rehabilitation training of patients with knee fractures. METHODS: Patients with knee fractures from July 2020 to July 2021 were randomly assigned to either the experimental group or a control group according to the double-blind principle. Both groups were given surgical treatment and postoperative conventional rehabilitation training. There were 40 cases in the control group, including 27 males and 13 females;the age ranged from 20 to 66 years old with an average of (36.46±6.29) years old, continuous passive motion (CPM) training was performed after operation. There were 40 patients in the experimental group, including 24 males and 16 females. The age ranged from 21 to 68 years old with an average of (37.62±7.08) years old, on the basis of the control group, electroacupuncture was given. After 4 weeks of intervention, the excellent rate of knee function score, visual analogue scale (VAS) before and after intervention, serum pain mediators, prostaglandin E (PGE), substance P (SP), bradykinin (BK), joint range of motion and quality of life were compared between the two groups. RESULTS: After 4 weeks of intervention, the Rasmussen score for knee function in the experimental group (24.15±1.36) scores was higher than that in the control group (21.25±2.20) scores (P<0.001). The VAS in the experimental group (2.04±0.51) scores was lower than that in the control group (2.78±0.60) after 4 weeks of intervention (P<0.05). Serum PGE (2.25±0.37) mg·L-1, SP (4.43±1.05) ng·ml-1, BK (2.67±0.68) ng·ml-1 in the experimental group were lower than those in the control group (3.91±0.44) mg·L-1, (6.12±1.37) ng·ml-1, (4.55±1.03) ng·ml-1 after 4 weeks of intervention(P<0.05);in the experimental group, the active knee flexion angle of the knee joint was (108.63±9.76)°, the active knee extension angle (-2.46±0.70)°, passive knee flexion angle (116.83±6.57)°, passive knee extension angle (1.44±0.38)° were better than control group (100.24±8.15)°, (-3.51±0.86)°, (111.04±8.22)°, (0.78±0.24)° (P<0.05);the experimental group's psychological score (73.12±5.08), physiological score (72.26±5.89), social function score (72.57±4.23), overall health score (75.12±5.16) were higher than that of the control group (68.49±4.13), (68.13±5.27), (69.04±3.42), and(70.88±3.97) respectvely(P<0.05). CONCLUSION: Electroacupuncture combined with CPM training after knee fracture surgery can significantly improve knee function and range of motion, reduce pain levels, and also improve quality of life and reduce the incidence of adverse events.

The azole biocide climbazole induces oxidative stress, inflammation, and apoptosis in fish gut.

Climbazole is an azole biocide that has been widely used in formulations of personal care products. Climbazole can cause developmental toxicity and endocrine disruption as well as gut disturbance in aquatic organisms. However, the mechanisms behind gut toxicity induced by climbazole still remain largely unclear in fish. Here, we evaluate the gut effects by exposing grass carp (Ctenopharyngodon idella) to climbazole at levels ranging from 0.2 to 20 µg/L for 42 days by evaluating gene transcription and expression, biochemical analyses, correlation network analysis, and molecular docking. Results showed that climbazole exposure increased cyp1a mRNA expression and ROS level in the three treatment groups. Climbazole also inhibited Nrf2 and Keap1 transcripts as well as proteins, and suppressed the transcript levels of their subordinate antioxidant molecules (cat, sod, and ho-1), increasing oxidative stress. Additionally, climbazole enhanced NF-κB and iκBα transcripts and proteins, and the transcripts of NF-κB downstream pro-inflammatory factors (tnfα, and il-1ß/6/8), leading to inflammation. Climbazole increased pro-apoptosis-related genes (fadd, bad1, and caspase3), and decreased anti-apoptosis-associated genes (bcl2, and bcl-xl), suggesting a direct reaction to apoptosis. The molecular docking data showed that climbazole could form stable hydrogen bonds with CYP1A. Mechanistically, our findings suggested that climbazole can induce inflammation and oxidative stress through CYP450s/ROS/Nrf2/NF-κB pathways, resulting in cell apoptosis in the gut of grass carp.

Neuroimaging research progress of acupuncture treatment for patients with functional dyspepsia. / é’ˆåˆºæ²»ç–—åŠŸèƒ½æ€§æ¶ˆåŒ–ä¸è‰¯çš„ç¥žç»å½±åƒå­¦ç ”ç©¶è¿›å±•.

Neuroimaging technology provides objective and visualized research tool to study the mechanisms of acupuncture effects. Building on a systematic review of previous clinical studies on acupuncture treatment for functional dyspepsia using neuroimaging technology, this paper summarizes and synthesizes past researches from 4 aspects： acupoint-specific effects, factors influencing the effects, different physiological responses, and predictive factors for acupuncture efficacy. It suggests that acupuncture treatment for FD involves central integration with disease-targeted (acupuncture treatment can target and regulate abnormal brain functional activity patterns in patients with FD), meridian-specific (stimulation of specific acupuncture points along the stomach meridian can significantly regulate abnormal brain functional activity patterns in FD patients), and dynamic conditional features(the effects of acupuncture treatment for FD are influenced by multiple factors). Lastly, considering the current research status, this paper outlines prospects in terms of research subjects, influencing factors, and result validation, aiming to provide references for future in-depth research.

Structural analysis of a soluble polysaccharide GSPA-0.3 from the root of Panax ginseng C. A. Meyer and its adjuvant activity with mechanism investigation.

A novel polysaccharide (GSPA-0.3) was isolated and purified from the root of cultivated Panax ginseng C. A. Meyer, and its structure, adjuvant activities, and mechanisms for inducing the maturation of mouse dendritic 2.4 cells (DC2.4) were extensively studied. Fraction GSPA-0.3, mainly composed by the galacturonic acid, galactose, arabinose, glucose, rhamnose, mannose, and xylose, had a molecular weight of 62,722 Da. The main chain of GSPA-0.3 was composed of →3)-α-L-Rhap-(1→, →4)-α-D-GalpA-(1→, and →3, 4)-α-D-GalpA-(1→. Branched chains comprised α-L-Araf-(1→3, 5)-α-L-Araf-(1→5)-α-L-Araf-(1→, α-D-Glcp-(1→6)-α-D-Glcp-(1→6)-α-D-Glcp-(1→, ß-D-Galp-(1→4)-ß-D-Galp-(1→4)-ß-D-Galp-(1→, and α-D-GalpA-(1→ units connected to the C3 position of →3, 4)-α-D-GalpA-(1→. In vivo, GSPA-0.3 was found to stimulate the production of IgG, IgG1, and IgG2a; increase the splenocyte proliferation index; and promote the expression of GATA-3, T-bet, IFN-γ, and IL-4 in H1N1 vaccine-immunized mice. Moreover, GSPA-0.3 significantly increased the levels of neutralizing antibodies in the mice, and its adjuvant activity was found to be superior to aluminum adjuvant (Alum adjuvant). Mechanistic investigations showed that GSPA-0.3 activated the TLR4-dependent pathway by upregulating the expressions of TLR4, MyD88, TRAF-6, and NF-κB proteins and gens. The results presented herein suggested that GSPA-0.3 could significantly promote the efficacy of the H1N1 vaccine by modulating Th1/Th2 response via the TLR4-MyD88-NF-κB signaling pathway.

Design and synthesis of dabigatran etexilate derivatives with inhibiting thrombin activity for hepatocellular carcinoma treatment.

Hepatocellular carcinoma (HCC) is one of the most fatal solid malignancies worldwide. Evidence suggests that thrombin stimulates tumor progression via fibrin formation and platelet activation. Meanwhile, we also found a correlation between thrombin and HCC through bioinformatics analysis. Dabigatran is a selective, direct thrombin inhibitor that reversibly binds to thrombin. Dabigatran was used as the lead agent in this study, and 19 dabigatran derivatives were designed and synthesized based on docking mode. The thrombin-inhibitory activity of the derivative AX-2 was slightly better than that of dabigatran. BX-2, a prodrug of AX-2, showed a fairly strong inhibitory effect on thrombin-induced platelet aggregation, and effectively antagonized proliferation of HCC tumor cells induced by thrombin at the cellular level. Furthermore, BX-2 reduced tumor volume, weight, lung metastasis, and secondary tumor occurrence in nude mouse models. BX-2 combined with sorafenib increased sorafenib efficacy. This study lays the foundation for discovering new anti-HCC mechanism based on thrombin. BX-2 can be used as an anti-HCC drug lead for further research.

Chemical constitutes from Tuber indicum with immunosuppressive activity uncovered by transcriptome analysis.

Three previously undescribed compounds including a polyketide (1) and two lactams (2 and 3) were obtained from Tuber indicum. The structures of new findings were elucidated by HRESIMS, NMR as well as NMR and ECD calculations. Transcriptome analysis through RNA-seq revealed that compound 2 exhibits immunosuppressive activity. Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were employed as a model to explore the effect of these compounds in immunosuppressive activity. The results showed that 2 could reduce the generation of inflammatory mediators including nitric oxide (NO), reactive oxygen species (ROS), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Western blotting analysis demonstrated that 2 could suppressed the PI3K pathway by decreasing the levels of p-PI3K and p-Akt, while increasing the levels of p-PTEN. The anti-inflammatory activity of 2 was further confirmed using a zebrafish in vivo model.

Spectrum-Effect Relationship in Chinese Herbal Medicine: Current Status and Future Perspectives.

The quality of Chinese herbal medicine (CHM) directly impacts clinical efficacy and safety. Fingerprint technology is an internationally recognized method for evaluating the quality of CHM. However, the existing quality evaluation models based on fingerprint technology have blocked the ability to assess the internal quality of CHM and cannot comprehensively reflect the correlation between pharmacodynamic information and active constituents. Through mathematical methods, a connection between the "Spectrum" (fingerprint) and the "Effect" (pharmacodynamic data) was established to conduct a spectrum-effect relationship (SER) of CHM to unravel the active component information associated with the pharmacodynamic activity. Consequently, SER can efficiently address the limitations of the segmentation of chemical components and pharmacodynamic effect in CHM and further improve the quality evaluation of CHM. This review focuses on the recent research progress of SER in the field of CHM, including the establishment of fingerprint, the selection of data analysis methods, and their recent applications in the field of CHM. Various advanced fingerprint techniques are introduced, followed by the data analysis methods used in recent years are summarized. Finally, the applications of SER based on different research subjects are described in detail. In addition, the advantages of combining SER with other data are discussed through practical applications, and the research on SER is summarized and prospected. This review proves the validity and development potential of the SER and provides a reference for the development and application of quality evaluation methods for CHM.

Effects of Yoga on Cancer-Related Fatigue, Psychological Distress, and Quality of Life Among Patients With Cancer Undergoing Chemotherapy and/or Radiotherapy: A Systematic Review and Meta-analysis.

BACKGROUND: Yoga can be considered supportive therapy for patients with cancer to alleviate cancer-related symptoms. However, there has been no meta-analysis examining yoga's effects among patients with cancer undergoing chemotherapy and/or radiotherapy. OBJECTIVE: To synthesize the evidence regarding the effects of yoga on improving cancer-related fatigue, psychological distress, and quality of life among patients with cancer undergoing chemotherapy and/or radiotherapy. METHODS: Ten English databases and 2 Chinese databases were searched from inception to December 2022. Two independent reviewers screened studies and extracted the data. Randomized controlled trials examining the effects of yoga on cancer-related fatigue, psychological distress, and quality of life were included. Meta-analysis was conducted, and narrative synthesis was performed when meta-analysis was not applicable. RESULTS: Fourteen studies from 16 articles were included. The results showed that yoga reduced cancer-related fatigue (standardized mean difference [SMD], -0.75; 95% confidence interval [CI], -1.12 to -0.38; P < .001), anxiety (SMD, -0.91; 95% CI, -1.68 to -0.14; P = .02), but not depression (SMD, -0.82; 95% CI, -1.67 to 0.04; P = .06). The effects of yoga on distress and quality of life were inconclusive. CONCLUSIONS: Yoga significantly helped reduce cancer-related fatigue and anxiety but did not reduce depression among patients with cancer undergoing chemotherapy and/or radiotherapy. Further rigorous studies are needed to identify the optimal characteristics of yoga for these patients. IMPLICATIONS FOR PRACTICE: It is possible to recommend yoga to patients with cancer undergoing chemotherapy and/or radiotherapy for managing cancer-related fatigue and anxiety after duly considering patients' physical conditions and ensuring appropriate instructions are given.

[Quality evaluation of Lysimachiae Herba from different habitats based on simultaneous determination of multiple bioactive constituents combined with multivariate statistical analysis].

A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 µm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.

Active ingredients of Erhuang Quzhi Granules for treating non-alcoholic fatty liver disease based on the NF-κB/NLRP3 pathway.

Erhuang Quzhi Granules (EQG), the Chinese herbal compound, has demonstrated significant clinical efficacy in treating non-alcoholic fatty liver disease (NAFLD). The mechanism of this treatment has been shown to involve the nuclear factor kappa B (NF-κB)/nod-like receptor thermal protein domain associated protein 3 (NLRP3) pathway. However, research on the material basis of EQG against NAFLD is still in its primary stages. Following these considerations, this study predicted and screened the active ingredients of EQG using the absorption, distribution, metabolism, and excretion (ADME) property evaluation tool and molecular docking. Then the levels of these active ingredients in EQG were measured using ultra-high-performance liquid chromatography (UHPLC). The efficacy of the active ingredients and their mechanisms were validated through both in vivo and in vitro experiments. The results indicate that the collected 12 components have favorable metabolic stability, are safe, and have drug-like properties. Aloe-emodin (AE), rhein (RH), curcumin (CUR), emodin (EM), and chrysophanol (CP) showed better binding affinity with TNF-α and Caspase-1 proteins. UHPLC analysis revealed that EQG contains AE, RH, CUR, EM, and CP. Cellular experiments proved that all these five ingredients reduce the accumulation of lipids and reactive oxygen species. In animal models of NAFLD, AE, and RH significantly improved the pathological symptoms of steatosis and fibrosis and reduced the levels of pro-inflammatory factors via the NF-κB/NLRP3 pathway. The results reveal the active ingredients of EQG for treating NAFLD based on the NF-κB/NLRP3 pathway and lay the foundation for the clinical promotion of EQG.

Effects of Phosphorus-dissolving Dark Septate Endophytes on the Growth of Blueberry.

Dark septate endophytes (DSEs) are widely distributed and improve plant growth. DSEs secrete large amounts of enzymes to mineralize insoluble phosphorus in soil and convert it into soluble phosphorus, promoting plant uptake of phosphorus. However, the effects of DSEs with phosphate-solubilizing ability on host plants need further study. In this study, phosphorus-dissolving DSEs were screened for growth-promoting effects. We isolated, identified and characterized three DSE species (Thozetella neonivea, Pezicula ericae and Hyaloscyphaceae sp.) showing phosphate-solubilizing ability. The impact of single, dual or triple inoculation of DSEs on blueberry plant characteristics was studied. Their effects on colonization intensity, seedling biomass, nutrients in plants and soil, and activities of plant resistance enzymes and soil enzymes were markedly upregulated relative to the control (P < 0.05). The available phosphorus and acid phosphatase levels in different combinations were significantly increased. These findings indicate that the application of the three DSEs may be valuable in facilitating the cultivation of blueberry with a higher biomass and improved plant quality.

Wastewater treatment plant effluents exert different impacts on antibiotic resistome in water and sediment of the receiving river: Metagenomic analysis and risk assessment.

Wastewater treatment plants (WWTPs) are considered as hotspots for the spread of antibiotic resistome into the environment. However, the differential contributions of WWTPs to the antibiotic resistome in the receiving river water and sediment are poorly understood. Here, based on metagenomic analysis, we found that the WWTP effluents significantly elevated the diversities and abundances of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in the receiving river water from the Qinghai-Tibet Plateau, but showed less interference with the antibiotic resistome in sediment. Estimated by SourceTracker, WWTPs contributed 60.691.8% of ARGs in downstream river water, much higher than those for sediment (7.7568.0%). A holistic comparison of ARG risks based on analysis of ARG combination, mobility risk, ARG hosts and ARG-carrying pathogens further revealed the great impacts of WWTP effluents on downstream river water rather than sediment. Among various MGEs, tnpA exhibited the greatest potential for the dissemination of ARGs, and displayed highest co-occurrence frequency with multiple ARGs. P. aeruginosa, E. cloacae, and E. coli were identified as the critical-priority pathogens of ARG hosts. This study demonstrated the much greater impacts of WWTP effluents on the downstream water compared with sediment, which is significant for developing effective strategies to mitigate ARG risks.

Aggressive variant prostate cancer: A case report and literature review.

BACKGROUND: Aggressive variant prostate cancer (AVPC) is a rare disease that progresses rapidly. The first-line treatment for AVPC is currently unknown. We examined a rare case of AVPC with rare brain and bladder metastases. A summary review of the mechanism of development, clinicopathological manifestations, associated treatments and prognosis of this disease is presented. CASE SUMMARY: The patient was diagnosed with prostate cancer (PCA), and was actively treated with endocrine therapy, radiotherapy, chemotherapy, and traditional Chinese medicine. Unfortunately, he was insensitive to treatment, and the disease progressed rapidly. He died five years after being diagnosed with PCA. CONCLUSION: We should reach consensus definitions of the AVPC and other androgen receptor-independent subtypes of PCA and develop new biomarkers to identify groups of high-risk variants. It is crucial to complete a puncture biopsy of the tumor or metastatic lesion as soon as possible in patients with advanced PCA who exhibit clinical features such as low Prostate-specific antigen levels, high carcinoembryonic antigen levels, and insensitivity to hormones to determine the pathological histological type and to create a more aggressive monitoring and treatment regimens.

Acupoint Thread Embedding Combined With Wenshen Bugu Decoction for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptom Among Postmenopausal Breast Cancer Patients: Study Protocol of a Randomized Controlled Trial.

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.

Combinatorics-based chemical characterization and bioactivity comparison of different parts of traditional Chinese medicinal plants through LC-Q-TOF-MS/MS, multivariate statistical analysis and bioassay: Marsdenia tenacissima as an example.

Marsdenia tenacissima is a traditional Chinese medicinal plant used for treating cancer, and its main medicinal part is the stem. Considering the resource shortage of M. tenacissima, it is of great significance to improve its utilization efficiency. Steroids and caffeoylquinic acids, the two main components of M. tenacissima, are composed of several basic structures. Based on this rule, a novel strategy of combinatorics-based chemical characterization was proposed to analyze the constituents of roots, stems and leaves of M. tenacissima. Combinatorics was used to generate a compound library for structure alignment, which has the advantages of wide coverage and high specificity. Steroids are composed of four basic parts: core skeleton (C), substituent at position 11 (A), substituent at position 12 (B) and sugar moiety (S). Based on combinatorics, a compound library consisting of 1080 steroids was generated. Diagnostic neutral loss has been used to effectively predict the substituents at position 11 and 12 of steroids, including acetyl, 2-methylpropionyl, tigloyl, 2-methylbutyryl and benzoyl. As a result, 131, 131 and 99 components were detected from the roots, stems and leaves of M. tenacissima, respectively. Principal component analysis (PCA) was used to analyze the differences of roots, stems and leaves, and orthogonal partial least squares-discriminant analysis (OPLS-DA) was further applied to find differential components. Tenacissoside H, a critical indicator component for quality evaluation of the stem, has been proved to be a differential component between roots and stems. Notably, the relative content of tenacissoside H in the roots was significantly higher than that in the stems. The bioactivity comparison showed that roots, stems and leaves of M. tenacissima had similar scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. However, their α-glucosidase inhibitory activity was ranked as leaves > stems > roots. Therefore, besides stems, the other parts of M. tenacissima have potential medicinal value. This study not only helps to develop the resource of M. tenacissima, but also provides a paradigm for the research of other similar medicinal plants.

Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium.

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION: DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.

Antihyperuricemic and Renal Protective Effect of Cordyceps chanhua (Ascomycetes) Fruiting Bodies in Acute Hyperuricemia and Chronic Gout Rodent Models.

Cordyceps chanhua has been widely used in traditional Chinese medicine. The uric acid-lowering effect of artificially cultivated fruiting bodies of C. chanhua (FBCC) was studied using the acute hyperuricemia (AH) and chronic gout (CG) animal models. The AH mice and CG rats were randomly divided into 6 groups: the negative control group, model group, positive control group, low-dose group, medium-dose group, and high-dose group of FBCC, respectively. Serum uric acid, creatinine, urea nitrogen, and liver xanthine oxidase (XOD) activity were detected. Renal tubulointerstitial injury and urate crystals in CG rats were evaluated. The results showed that the uric acid content in AH mice with the high-dose FBCC group decreased statistically (P < 0.05). In the CG rats, the serum uric acid level in all FBCC groups and the serum creatinine value in the high-dose group exhibited a significant decrease (P < 0.05); the scores of renal tubulointerstitial damage and urate deposit were reduced in the high-dose group of FBCC. FBCC can reduce uric acid and improve renal function, demonstrating it as a beneficial supplement for uric acid-lowering and gout-relieving drugs.

Antitumor effects of polysaccharides from medicinal lower plants: A review.

Cancer is one of the leading causes of death worldwide, yet the drugs currently approved for cancer treatment are associated with significant side effects, making it urgent to develop alternative drugs with low side effects. Polysaccharides are natural polymers with ketone or aldehyde groups, which are widely found in plants and have various biological activities such as immunomodulation, antitumor and hypolipidemic. The lower plants have attracted much attention for their outstanding anticancer effects, and many studies have shown that medicinal lower plant polysaccharides (MLPPs) have antitumor activity against various cancers and are promising alternatives with potential development in the food and pharmaceutical fields. Therefore, this review describes the structure and mechanism of action of MLPPs with antitumor activity. In addition, the application of MLPPs in cancer treatment is discussed, and the future development of MLPPs is explored.

[Analysis and evaluation of bioactive constituents from different parts of Epimedium brevicornum].

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 µm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.