Chinese patent medicine as a complementary and alternative therapy for type 2 diabetes mellitus: A scoping review.

OBJECTIVE: This scoping review aims to document Chinese Patent Medicines (CPMs) for Type 2 Diabetes Mellitus, explore whether CPMs can improve patients' health outcomes, and set priorities in addressing research gaps in this area. METHODS: Following the framework of PRISMA-SCr, we proposed the research questions based on PICOS principle, and searched the CPMs for T2DM from three drug lists, followed by a systematic search of the literature in eight databases from their inception to June 22, 2023. Then, we developed the eligibility criteria and systematically reviewed the relevant studies, retained the studies about CPMs for T2DM, extracted the related data, and identified the differences across studies in structured charts. RESULTS: A total of 25 types of CPMs were extracted from the three drug lists. Radix astragali appeared most frequently (19 times) among the herbal medicinal ingredients of CPMs. A total of 449 articles were included in the full-paper analysis ultimately, all of which were about 20 types of CPMs, and there were no related reports on the remaining five CPMs. Except about a quarter (25.39 %, 114/449) using CPMs alone, the remaining studies all involved the combination with oral hypoglycemics for T2DM. Biguanides are the most common drugs used in combination with CPMs (50.14 %, 168/335). Fasting plasma glucose (FPG) is the most frequently reported outcomes in efficacy evaluation (82.41 %, 370/449). CONCLUSION: There are a total of 25 types of CPMs currently available for T2DM patients. However, the volume of related evidence on these CPMs varies. It is necessary to standardize the combined use of CPMs and conventional medicine and select appropriate outcomes in future studies.

Effect of electroacupuncture at the acupoints for Tiaozang Xingshen on cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction. / "调脏醒神"电针对2åž‹ç³–å°¿ç— ç›¸å ³è®¤çŸ¥åŠŸèƒ½éšœç¢æ‚£è€ è„‘å† ä»£è°¢çš„å½±å“.

OBJECTIVES: To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy. METHODS: Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined；with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm. RESULTS: Before treatment, compared with the control group, in the observation group, MoCA score was lower (P<0.001), CDR score and the levels of FPG and HbA1c were higher (P<0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged (P<0.05, P<0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased (P<0.05, P<0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped (P<0.001), and that of myo-inositol (MI) to Cr in the right side increased (P<0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher (P<0.001), the scores of CDR, SAS and HAMD were reduced (P<0.01, P<0.05), the reaction times of Flanker conflict and Stroop conflict shortened (P<0.001, P<0.05), and the accuracy of Flanker conflict and 1-back increased (P<0.001, P<0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased (P<0.05), that of MI to Cr in the right decreased (P<0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence (r=0.671, P=0.012) and this ratio was positively correlated with the reaction time of Stroop conflict (r=0.576, P=0.039). CONCLUSIONS: Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.

Ginseng-derived nanoparticles reprogram macrophages to regulate arginase-1 release for ameliorating T cell exhaustion in tumor microenvironment.

BACKGROUND: Lines of evidence indicated that, immune checkpoints (ICs) inhibitors enhanced T cell immune response to exert anti-tumor effects. However, T cell exhaustion has been so far a major obstacle to antitumor immunotherapy in colorectal cancer patients. Our previous studies showed that ginseng-derived nanoparticles (GDNPs) inhibited the growth of various tumors by reprograming tumor-associated macrophages (TAMs) and downregulated the ICs expression on T cells in tumor microenvironment (TME), but the underlying effector mechanisms remained unclear. METHODS: The correlation between arginase-1 (ARG1) and T cells was computed based on the colorectal cancer patients in TCGA database. In vitro, we observed that GDNPs reprogrammed TAMs inhibited ARG1 release and ultimately ameliorated T cell exhaustion according to several techniques including WB, PCR, ELISA and flow cytometry. We also used an in vivo MC38 tumor-bearing model and administered GDNPs to assess their anti-tumor effects through multiple indices. The mechanism that GDNPs improved T cell exhaustion was further clarified using the bioinformatics tools and flow cytometry. RESULTS: GDNPs reprogramed TAMs via reducing ARG1 production. Moreover, normalized arginine metabolism ameliorated T cell exhaustion through mTOR-T-bet axis, resulting in reduced ICs expression and enhanced CD8+ T cells expansion. CONCLUSIONS: By regulating the mTOR-T-bet axis, GDNPs reprogramed macrophages to regulate ARG1 release, which further ameliorated T cell exhaustion in TME. These findings provided new insights into comprehending the mechanisms underlying the mitigation of T cell exhaustion, which may facilitate the development of innovative therapeutic strategies in the field of cancer treatment.

Somatic acupressure for the fatigue-sleep disturbance-depression symptom cluster in breast cancer survivors: A phase II randomized controlled trial.

OBJECTIVE: To evaluate the feasibility of the somatic acupressure (SA) for managing the fatigue-sleep disturbance-depression symptom cluster (FSDSC) among breast cancer (BC) survivors and its preliminary effects. METHODS: In this Phase II randomized controlled trial (RCT), 51 participants were randomised evenly into the true SA group, sham SA group, and usual care group. All the participants received usual care. The two SA groups performed additional true or sham self-acupressure daily for seven weeks. The primary outcomes related to the assessment of participants' recruitment and compliance with study questionnaires and interventions. Clinical outcomes assessed the preliminary effects of SA on fatigue, sleep disturbance, depression, and quality of life. Semi-structured interviews were undertaken to capture participants' experiences of participating in this study. The statistical effects of the intervention on the outcomes were modelled in repeated measures ANOVA and adjusted generalized estimating equations. RESULTS: Forty-five participants completed the SA intervention. No adverse events were reported. Over 85% of the participants could sustain for 25 days or more and 15 min or more per session, but the adherence to the intervention requirement was yet to improve. The group by time effect of the FSDSC and depression were significant (p < 0.05). Qualitative findings showed that participants positively viewed SA as a beneficial strategy for symptom management. CONCLUSIONS: The SA intervention protocol and the trial procedures were feasible. The results demonstrated signs of improvements in targeted outcomes, and a full-scale RCT is warranted to validate the effects of SA on the FSDSC.

Therapeutic potential of Coptis chinensis for arthritis with underlying mechanisms.

Arthritis is a common degenerative disease of joints, which has become a public health problem affecting human health, but its pathogenesis is complex and cannot be eradicated. Coptis chinensis (CC) has a variety of active ingredients, is a natural antibacterial and anti-inflammatory drug. In which, berberine is its main effective ingredient, and has good therapeutic effects on rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis (GA). RA, OA and GA are the three most common types of arthritis, but the relevant pathogenesis is not clear. Therefore, molecular mechanism and prevention and treatment of arthritis are the key issues to be paid attention to in clinical practice. In general, berberine, palmatine, coptisine, jatrorrhizine, magnoflorine and jatrorrhizine hydrochloride in CC play the role in treating arthritis by regulating Wnt1/ß-catenin and PI3K/AKT/mTOR signaling pathways. In this review, active ingredients, targets and mechanism of CC in the treatment of arthritis were expounded, and we have further explained the potential role of AHR, CAV1, CRP, CXCL2, IRF1, SPP1, and IL-17 signaling pathway in the treatment of arthritis, and to provide a new idea for the clinical treatment of arthritis by CC.

Near-Infrared-II Fluorophore with Inverted Dependence of Fluorescence Quantum Yield on Polarity as Potent Phototheranostics for Fluorescence-Image-Guided Phototherapy of Tumors.

Organic phototheranostics simultaneously having fluorescence in the second near-infrared (NIR-II, 1000-1700 nm) window, and photothermal and photodynamic functions possess great prospects in tumor diagnosis and therapy. However, such phototheranostics generally suffer from low brightness and poor photodynamic performance due to severe solvatochromism. Herein, an organic NIR-II fluorophore AS1, which possesses an inverted dependence of fluorescence quantum yield on polarity, is reported to serve as potent phototheranostics for tumor diagnosis and therapy. After encapsulation of AS1 into nanostructures, the obtained phototheranostics (AS1R ) exhibit high extinction coefficients (e.g., 68200 L mol-1  cm-1 at 808 nm), NIR-II emission with high fluorescence quantum yield up to 4.7% beyond 1000 nm, photothermal conversion efficiency of ≈65%, and 1 O2 quantum yield up to 4.1%. The characterization of photophysical properties demonstrates that AS1R is superior to other types of organic phototheranostics in brightness, photothermal effect, and photodynamic performance at the same mass concentration. The excellent phototheranostic performance of AS1R enables clear visualization and complete elimination of tumors using a single and low injection dose. This study demonstrates the merits and prospects of NIR-II fluorophore with inverted polarity dependence of fluorescence quantum yield as high-performance phototheranostic agents for fluorescence imaging and phototherapy of tumors.

Research methods and efficacy of acupuncture in the treatment of Parkinson's disease: a scoping review of systematic reviews and meta-analyses.

Introduction: Research on acupuncture for Parkinson's Disease is growing rapidly. A scoping review examines emerging evidence and is important to guide policy and practice. The purpose of this scoping review was to examine the breadth and methodological quality of systematic reviews and meta-analyses, and to map the quality of evidence of these studies to evaluate the efficacy of acupuncture for treatment of PD. Methods: Seven literature databases were searched. Two researchers independently screened the literature and extracted relevant information (such as general characteristics, inclusion criteria, study results, and report quality).The inclusion criteria include publicly published systematic reviews/meta-analyses/systematic reviews of acupuncture treatment for Parkinson's disease. The research subjects are any patients who meet the diagnostic criteria for Parkinson's disease, and intervention measures include acupuncture treatment including electro acupuncture, scalp acupuncture, or combination with other treatment methods. The outcome indicators are all types of results related to PD and the effective measurement tools used. Results: A total of 23 systematic reviews and/or meta-analyses of studies were included. Most of the articles were published between 2019 and 2023 (47.8%). A total of 14 articles (60.9%) were evaluated and classified, and 89 (36.8.1%) of the 242 included articles were of medium and high quality. Discussion: This study comprehensively evaluates the quality and research methods of incorporating SRs/MAs, and concludes that acupuncture treatment for Parkinson's disease may be significant. Considering the shortcomings in research design and methodology, it is not possible to draw conclusions on the evidence of acupuncture treatment for PD at this stage, but it does not mean that acupuncture treatment is ineffective. We hope to focus on improving research design and methods in the study of acupuncture treatment for Parkinson's disease, an increase the credibility of research results.

Natural flavonoids disrupt bacterial iron homeostasis to potentiate colistin efficacy.

In the face of the alarming rise in global antimicrobial resistance, only a handful of novel antibiotics have been developed in recent decades, necessitating innovations in therapeutic strategies to fill the void of antibiotic discovery. Here, we established a screening platform mimicking the host milieu to select antibiotic adjuvants and found three catechol-type flavonoids-7,8-dihydroxyflavone, myricetin, and luteolin-prominently potentiating the efficacy of colistin. Further mechanistic analysis demonstrated that these flavonoids are able to disrupt bacterial iron homeostasis through converting ferric iron to ferrous form. The excessive intracellular ferrous iron modulated the membrane charge of bacteria via interfering the two-component system pmrA/pmrB, thereby promoting the colistin binding and subsequent membrane damage. The potentiation of these flavonoids was further confirmed in an in vivo infection model. Collectively, the current study provided three flavonoids as colistin adjuvant to replenish our arsenals for combating bacterial infections and shed the light on the bacterial iron signaling as a promising target for antibacterial therapies.

Modified Xiaoyao San reverses lipopolysaccharide-induced depression-like behavior through suppressing microglia M1 polarization via enhancing autophagy involved in PI3K/Akt/mTOR pathway in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Xiaoyao San (MXYS), a clinical empirical modified formula based on famous traditional Chinese herbal prescription Xiaoyao San, according to the "yu syndrome" theory of traditional Chinese medicine. MXYS has been shown to be an excellent effective therapy for depression patients in clinic, but the antidepressant mechanisms remain unclear. AIM OF THE STUDY: A growing body of evidence indicates the microglia autophagy and M1 polarized microglia (proinflammatory phenotype)-mediated neuroinflammation act critical roles in the pathogenesis of depression. This study aimed to investigate whether MXYS exerts antidepressant efficacy through inhibition of M1 polarized microglia-mediated neuroinflammation and modulation of autophagy involved in PI3K/Akt/mTOR pathway. MATERIALS AND METHODS: In present research, the lipopolysaccharide (LPS)-induced depressive mice and LPS-stimulated N9 microglia cell line were utilized. Behavioral tests (sucrose preference, tail suspension and open field tests) were carried out to evaluate the antidepressant effect of MXYS. The neuronal damage was measured by Nissl's staining in LPS-treated mice. The proinflammatory cytokine levels, the autophagic markers, microglia M1 polarization as well as the PI3K/Akt/mTOR pathway related proteins of MXYS treatment were analyzed by ELISA kits, Western blot and immunofluorescence staining in vivo and vitro. Finally, the influence of autophagy antagonist (3-MA) on the protective effect of MXYS-containing serum in the LPS-stimulated N9 microglia was investigated. RESULTS: Treatment of LPS-induced depressive mice with MXYS significantly reversed depression-like behaviors, accompanied by reduction of proinflammatory cytokine levels (TNF-α, IL-1ß) and amelioration of neuronal damage in prefrontal cortex. MXYS suppressed microglia M1 polarization and promoted autophagy in prefrontal cortex and LPS-stimulated N9 cells. Importantly, the remarkable inhibitory effect of the MXYS-medicated serum on microglia M1 polarization was blocked by autophagy antagonist 3-MA in LPS-stimulated N9 cells. Meanwhile, the MXYS treatment exhibited an excellent inhibition effect of PI3K/Akt/mTOR pathway in vivo and vitro. CONCLUSION: Our research suggests that the antidepressant effect of MXYS in LPS-induced depressive mice may be related to alleviate neuroinflammation through suppression of microglia M1 polarization via enhancing autophagy involved in inactivation of the PI3K/Akt/mTOR pathway.

"Adjust Zang and arouse spirit" electroacupuncture ameliorates cognitive impairment by reducing endoplasmic reticulum stress in db/db mice.

Introduction: Diabetic cognitive impairment (DCI) is a chronic complication of the central nervous system (CNS) caused by diabetes that affects learning and memory capacities over time. Recently, acupuncture has been shown to improve cognitive impairment in streptozotocin-induced diabetic rats. However, the effects of electroacupuncture on DCI and its underlying mechanism have not yet been elucidated in detail. Methods: In this study, we used db/db mice as DCI animal models which showed low cognitive, learning and memory functions. Electroacupuncture significantly ameliorated DCI, which is reflected by better spatial learning and memory function using behavioral tests. The db/db mice with cognitive impairment were randomly divided into a model group (Mod) and an electroacupuncture treatment group (Acup), while db/m mice were used as a normal control group (Con). First, the mice were subjected to behavioural tests using the Morris water maze (MWM), and body weight, blood glucose, insulin, triglycerides (TG) and total cholesterol (TC) were observed; HE, Nissl, and TUNEL staining were used to observe the morphological changes and neuronal apoptosis in the mice hippocampus; Finally, Western blot and rt-PCR were applied to detect the essential proteins and mRNA of ERS and insulin signalling pathway, as well as the expression levels of Tau and Aß. Results: Electroacupuncture significantly ameliorated DCI, which is reflected by better spatial learning and memory function using behavioral tests. Moreover, electroacupuncture attenuated diabetes-induced morphological structure change, neuronal apoptosis in the hippocampus of db/db mice. Our results revealed that electroacupuncture could regulate the expression levels of Tau and Aß by improving hippocampal ERS levels in db/db mice, inhibiting JNK activation, attenuating IRS1 serine phosphorylation, and restoring normal transduction of the insulin signaling pathway. Discussion: In summary, ERS and insulin signaling pathway paly causal roles in DCI development. Electroacupuncture can significantly alleviate the pathogenesis of DCI, improve mice's learning and memory ability, and improve cognitive dysfunction. This study adds to our understanding of the effect of acupuncture on DCI and opens the door to further research on DCI.

Long non­coding RNA BLACAT2/miR­378a­3p/YY1 feedback loop promotes the proliferation, migration and invasion of uterine corpus endometrial carcinoma.

Uterine corpus endometrial carcinoma (UCEC) is a common gynecological malignancy with high rates of mortality and morbidity. The expression of long non­coding RNA bladder cancer­associated transcript 2 (BLACAT2) has been previously found to be aberrantly upregulated in UCEC. However, the regulatory consequences of this in UCEC progression remain poorly understood. In the present study, human UCEC cell lines AN3CA and HEC­1­A were infected with lentiviruses to overexpress BLACAT2 (Lv­BLACAT2) or knock down BLACAT2 using short hairpin RNA (Lv­shBLACAT2). BLACAT2 overexpression was found to promote the G1/S transition of cell cycle progression and UCEC cell proliferation. In addition, BLACAT2 overexpression was observed to facilitate UCEC cell migration and invasion. By contrast, BLACAT2 knockdown resulted in inhibitory effects in UCEC cell physiology. BLACAT2 overexpression also contributed to the activation of the MEK/ERK pathway. Subsequently, BLACAT2 was demonstrated to bind to microRNA (miR)­378a­3p according to dual­luciferase assays, where it appeared to function as a sponge of miR­378a­3p in 293T cells. miR­378a­3p overexpression was found to suppress UCEC cell proliferation, invasion, and ERK activation. Lentivirus­mediated knockdown of its target, the transcription factor Yin Yang­1 (YY1), was observed to reverse the oncogenic effects of BLACAT2 overexpression. Furthermore, YY1 was found to bind to the promoter of BLACAT2, suggesting that YY1 can regulate BLACAT2 expression. To conclude, results from the present study suggest that BLACAT2, miR­378a­3p and YY1 can form a feedback loop instead of an unidirectional axis, which can in turn regulate UCEC tumorigenesis through the MEK/ERK pathway. The present study furthered the understanding of UCEC tumorigenesis and may provide novel therapeutic targets for UCEC treatment.

Baicalin can enhance odonto/osteogenic differentiation of inflammatory dental pulp stem cells by inhibiting the NF-κB and ß-catenin/Wnt signaling pathways.

BACKGROUND: Scutellaria baicalensis Georgi is a famous traditional Chinese medicine, which is widely used in treating fever, upper respiratory tract infection and other diseases. Pharmacology study showed it can exhibit anti-bacterial, anti-inflammation and analgesic effects. In this study, we investigated the effect of baicalin on the odonto/osteogenic differentiation of inflammatory dental pulp stem cells (iDPSCs). METHODS AND RESULTS: iDPSCs were isolated from the inflamed pulps collected from pulpitis. The proliferation of iDPSCs was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2,5-tetrazolium bromide (MTT) assay and flow cytometry. Alkaline phosphatase (ALP) activity assay, alizarin red staining, Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay were conducted to examine the differentiation potency along with the involvement of nuclear factor kappa B(NF-κB) and ß-catenin/Wnt signaling pathway. MTT assay and cell-cycle analysis demonstrated that baicalin had no influence on the proliferation of iDPSCs. ALP activity assay and alizarin red staining demonstrated that baicalin could obviously enhance ALP activity and calcified nodules formed in iDPSCs. RT-PCR and Western blot showed that the odonto/osteogenic markers were upregulated in baicalin-treated iDPSCs. Moreover, expression of cytoplastic phosphor-P65, nuclear P65, and ß-catenin in iDPSCs was significantly increased compared with DPSCs, but the expression in baicalin-treated iDPSCs was inhibited. In addition, 20 µM Baicalin could accelerate odonto/osteogenic differentiation of iDPSCs via inhibition of NF-κB and ß-catenin/Wnt signaling pathways. CONCLUSION: Baicalin can promote odonto/osteogenic differentiation of iDPSCs through inhibition of NF-κB and ß-catenin/Wnt pathways, thus providing direct evidence that baicalin may be effective in repairing pulp with early irreversible pulpitis.

Effect of acupuncture on the modulation of functional brain regions in migraine: A meta-analysis of fMRI studies.

Background: Acupuncture, a traditional Chinese medicine therapy, is an effective migraine treatment, especially in improving pain. In recent years, many acupuncture brain imaging studies have found significant changes in brain function following acupuncture treatment of migraine, providing a new perspective to elucidate the mechanism of action of acupuncture. Objective: To analyse and summarize the effects of acupuncture on the modulation of specific patterns of brain region activity changes in migraine patients, thus providing a mechanism for treating migraine by acupuncture. Methods: Chinese and English articles published up to May 2022 were searched in three English databases (PubMed, Embase and Cochrane) and four Chinese databases (China national knowledge infrastructure, CNKI; Chinese Biomedical Literature database, CBM; the Chongqing VIP database, VIP; and the Wanfang database, WF). A neuroimaging meta-analysis on ALFF, ReHo was performed on the included studies using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software. Subgroup analyses were used to compare differences in brain regions between acupuncture and other groups. Meta-regression was used to explore the effect of demographic information and migraine alterations on brain imaging outcomes. Linear models were drawn using MATLAB 2018a, and visual graphs for quality evaluation were produced using R and RStudio software. Results: A total of 7 studies comprising 236 patients in the treatment group and 173 in the control group were included in the meta-analysis. The results suggest that acupuncture treatment helps to improve pain symptoms in patients with migraine. The left angular gyrus is hyperactivation, and the left superior frontal gyrus and the right superior frontal gyrus are hypoactivated. The migraine group showed hyperactivation in the corpus callosum compared to healthy controls. Conclusion: Acupuncture can significantly regulate changes in brain regions in migraine patients. However, due to the experimental design of neuroimaging standards are not uniform, the results also have some bias. Therefore, to better understand the potential mechanism of acupuncture on migraine, a large sample, multicenter controlled trial is needed for further study. In addition, the application of machine learning methods in neuroimaging studies could help predict the efficacy of acupuncture and screen migraine patients suitable for acupuncture treatment.

Simultaneous Determination of Phenylethanoid Glycosides and Antioxidant Activity of Syringa pubescens Turcz. from Different Geographical Origin in China.

A high-performance liquid chromatograph with diode array detector was established for the simultaneous determination of five phenylethanoid glycosides in Syringa pubescens Turcz. The optimal chromatographic conditions were achieved on a Zorbax C18 column using gradient elution with 0.5% aqueous acetic acid and acetonitrile as the mobile phase at the flow rate of 1.0 mL/min. The detection wavelength was developed as follows: 0-10 min, 276 nm; 10-45 min, 332 nm. The validation of the method including linearity, precision, stability, accuracy, repeatability and recovery was tested. The chemometric analysis including hierarchical cluster analysis and principal component analysis was employed to investigate the similarity and difference of samples from different geographical origin. The results revealed that S. pubescens samples were divided into four clusters based on the phenylethanoid glycosides contents. Antioxidant activity of extract was measured using three different methods including α,α-diphenyl-ß-picrylhydrazyl and 2,2-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) radical scavenging assays, and ferric reducing antioxidant power assay. Furthermore, different phenylethanoid glycosides exhibited different contribution to antioxidant capacities. This study provides a foundation for the quality evaluation and offers scientific data for the utilization of S. pubescens resources.

Analysis of In Vivo Existence Forms of Nardosinone in Mice by UHPLC-Q-TOF-MS Technique.

Nardosinone, a sesquiterpene peroxide, is one of the main active constituents of the ethnomedicine Nardostachyos Radix et Rhizoma, and it has many bioactivities, such as antiarrhythmia and cardioprotection. To elucidate its in vivo existence forms, its metabolism is first studied using mice. All urine and feces are collected during the six days of oral dosing of nardosinone, and blood is collected at one hour after the last dose. Besides, to validate some metabolites, a fast experiment is performed, in which nardosinone was orally administered and the subsequent one-hour urine is collected and immediately analyzed by UHPLC-Q-TOF-MS. In total, 76 new metabolites are identified in this study, including 39, 51, and 12 metabolites in urine, plasma, and feces, respectively. Nardosinone can be converted into nardosinone acid or its isomers. The metabolic reactions of nardosinone included hydroxylation, hydrogenation, dehydration, glucuronidation, sulfation, demethylation, and carboxylation. There are 56 and 20 metabolites with the structural skeleton of nardosinone and nardosinone acid, respectively. In total, 77 in vivo existence forms of nardosinone are found in mice. Nardosinone is mainly excreted in urine and is not detected in the feces. These findings will lay the foundation for further research of the in vivo effective forms of nardosinone and Nardostachyos Radix et Rhizoma.

Potential therapeutic effects and applications of Eucommiae Folium in secondary hypertension.

Eucommiae Folium (EF), a traditional Chinese medicine, has been used to treat secondary hypertension, including renal hypertension and salt-sensitive hypertension, as well as hypertension caused by thoracic aortic endothelial dysfunction, a high-fat diet, and oxidized low-density lipoprotein. The antihypertensive components of EF are divided into four categories: flavonoids, iridoids, lignans, and phenylpropanoids, such as chlorogenic acid, geniposide acid and pinoresinol diglucoside. EF regulates the occurrence and development of hypertension by regulating biological processes, such as inhibiting inflammation, regulating the nitric oxide synthase pathway, reducing oxidative stress levels, regulating endothelial vasoactive factors, and lowering blood pressure. However, its molecular antihypertensive mechanisms are still unclear and require further investigation. In this review, by consulting the relevant literature on the antihypertensive effects of EF and using network pharmacology, we summarized the active ingredients and pharmacological mechanisms of EF in the treatment of hypertension to clarify how EF is associated with secondary hypertension, the related components, and underlying mechanisms. The results of the network pharmacology analysis indicated that EF treats hypertension through a multi-component, multi-target and multi-pathway mechanism. In particular, we discussed the role of EF targets in the treatment of hypertension, including epithelial sodium channel, heat shock protein70, rho-associated protein kinase 1, catalase, and superoxide dismutase. The relevant signal transduction pathways, the ras homolog family member A (RhoA)/Rho-associated protein kinase (ROCK) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase/eNOS/NO/Ca2+ pathways, are also discussed.

Influence of Chinese Herbal Formula on Bone Characteristics of Cobb Broiler Chickens.

To evaluate the prevention and treatment effect of a Chinese herbal formula (CHF) on the bone disease of Cobb broiler chickens, compare its efficacy with Bisphosphonates (BPs), and provide a theoretical basis for studying the nutritional regulation technology of CHF to improve the bone characteristics of broiler chickens. In this study, 560 one-day-old Cobb broiler chickens were examined for the influence of Chinese herbal formula (CHF) and Bisphosphonates (BPs). Different doses of CHF and BPs were added to the diet, and the 30- and 60-day-old live weight, tibial bone strength, the microstructure of the distal femur cancellous bone, blood biochemical indexes related to bone metabolism, and genes related to bone metabolism were determined and analyzed. The results showed that the live weight of Cobb broilers fed with CHF and BPs in the diet was as follows: The live weight of the CHF group was higher than that of the normal control (NC) group, while the live weight of the BPs group was lower than that of the NC group; the CHF and BPs improved the bone strength of Cobb broilers and increased the elastic modulus, yield strength, and maximum stress of the tibia. CHF and BPs increased the cancellous bone mineral density (BMD), bone tissue ratio (BV/TV), bone surface area tissue volume ratio (BS/TV), bone trabecular thickness (Tb.Th), and bone trabecular number (Tb.N) in the distal femur, and decreased the bone surface area bone volume ratio (BS/BV) and bone trabecular separation (Tb.Sp). Thus, the microstructure of the bone tissue of the distal femur was improved to a certain extent. Both the CHF and the BPs also increased the serum levels of the vitamin D receptor (VDR), osteoprotegerin (OPG), and alkaline phosphatase (ALP), and decreased the content of osteocalcin (OT). Meanwhile, CHF and BPs upregulated the expression of osteogenic genes (BMP-2, OPG, Runx-2) to promote bone formation and downregulated the expression of osteoclastic genes (RANK, RANKL, TNF-α) to inhibit bone resorption, thus affecting bone metabolism. Conclusion: The CHF could improve the skeletal characteristics of Cobb broilers by upregulating the expression of bone-forming-related genes and downregulating the expression of bone-breaking-related genes, thus preventing and controlling skeletal diseases in Cobb broilers. Its effect was comparable to that of BPs. Meanwhile, the CHF-H group achieved the best results in promoting the growth and improvement of the skeletal characteristics of Cobb broilers based on the live weight and skeletal-characteristics-related indexes.

Phthalocyanine-Based Nanoassembly with Switchable Fluorescence and Photoactivities for Tumor Imaging and Phototherapy.

Switchable theranostics are of great interest for accurate tumor imaging and targeted therapy. Here, we develop smart engineering to construct nanostructured phthalocyanines self-assembled by amphiphilic zinc phthalocyanines (ZnPcs) and hydrophobic copper phthalocyanines (CuPcs) (ZnPc(PEG)5:CuPc-N, where ZnPc(PEG)5 is monosubstituted ZnPcs with pentaethylene glycol as the substituent). The fluorescence and reactive oxygen species generation of ZnPc(PEG)5:CuPc-N can be triggered depending on the membrane of the tumor cells for the imaging and photoactivities. Concerning the stability in blood circulation, the surface of the nanocomplex is coated with polydopamine, which responds to the tumor acidic microenvironment. ZnPc(PEG)5 and CuPc focus on photodynamic and photothermal properties, respectively, and can be stimulated by a single laser beam, endowing ZnPc(PEG)5:CuPc-N a combined antitumor effect from evaluations both in vitro and in vivo. In our study, the mechanism of switchable theranostics, the strategy of combined photodynamic and photothermal therapy, and the smart nanoengineering technology of phthalocyanines with poor water solubility can be applied to other phthalocyanines or phthalocyanine-like phototherapy agents.

Photodynamic antitumor activity of Gallium(III) and Phosphorus(V) complexes of trimethoxyl A2B triaryl corrole.

Two new trimethoxyl A2B triaryl corroles 10-(2,4,6-trimethoxyphenyl)-5,15-bis(pentafluorophenyl)- corrole (1) and 10-(3,4,5-trimethoxyphenyl)-5,15-bis(pentafluorophenyl)-corrole (2) and their gallium(III) and phosphorus(V) (1-Ga, 1-P, 2-Ga and 2-P) complexes had been prepared and well characterized by UV-vis, NMR and HR-MS. Among all compounds, 2-Ga, 1-P and 2-P showed excellent in vivo photodynamic activity against the MDA-MB-231, A549, Hela and HepG2 cell lines upon light irradiation at 625 nm. And 2-P even exhibited higher phototoxicity than the clinical photosensitizer temoporfin. Also, 2-P exhibited the highest singlet oxygen quantum yield and photostability. The preliminary investigation revealed that 2-P could be rapidly absorbed by tumor cells and mainly located in the cytoplasm. After photodynamic therapy (PDT) treatment with 2-P, mitochondrial membrane potential destruction, intracellular ROS level increasing and nuclear fragmentation of cancer cells could be observed. Cell cycle analysis demonstrated that the 2-P PDT may cause tumor cell arrest at sub-G1 stage and induce early and late apoptosis of cells. These results suggest that 2-P is a promising candidate as a photosensitizer for photodynamic therapy.

Effect of acupuncture on brain regions modulation of mild cognitive impairment: A meta-analysis of functional magnetic resonance imaging studies.

Background: As a non-pharmacological therapy, acupuncture has significant efficacy in treating Mild Cognitive Impairment (MCI) compared to pharmacological therapies. In recent years, advances in neuroimaging techniques have provided new perspectives to elucidate the central mechanisms of acupuncture for MCI. Many acupuncture brain imaging studies have found significant improvements in brain function after acupuncture treatment of MCI, but the underlying mechanisms of brain regions modulation are unclear. Objective: A meta-analysis of functional magnetic resonance imaging studies of MCI patients treated with acupuncture was conducted to summarize the effects of acupuncture on the modulation of MCI brain regions from a neuroimaging perspective. Methods: Using acupuncture, neuroimaging, magnetic resonance, and Mild Cognitive Impairment as search terms, PubMed, EMBASE, Web of Science, Cochrane Library, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects (DARE), Google Scholar, China National Knowledge Infrastructure (CNKI), China Biology Medicine disk (CBM disk), Wanfang and Chinese Scientific Journal Database (VIP) for brain imaging studies on acupuncture on MCI published up to April 2022. Voxel-based neuroimaging meta-analysis of fMRI data was performed using voxel-based d Mapping with Permutation of Subject Images (SDM-PSI), allowing for Family-Wise Error Rate (FWER) correction correction for correction multiple comparisons of results. Subgroup analysis was used to compare the differences in brain regions between the acupuncture treatment group and other control groups. Meta-regression was used to explore demographic information and altered cognitive function effects on brain imaging outcomes. Linear models were drawn using MATLAB 2017a, and visual graphs for quality evaluation were produced using R software and RStudio software. Results: A total of seven studies met the inclusion criteria, with 94 patients in the treatment group and 112 patients in the control group. All studies were analyzed using the regional homogeneity (ReHo) method. The experimental design of fMRI included six task state studies and one resting-state study. The meta-analysis showed that MCI patients had enhanced activity in the right insula, left anterior cingulate/paracingulate gyri, right thalamus, right middle frontal gyrus, right median cingulate/paracingulate gyri, and right middle temporal gyrus brain regions after acupuncture treatment. Further analysis of RCT and longitudinal studies showed that Reho values were significantly elevated in two brain regions, the left anterior cingulate/paracingulate gyrus and the right insula, after acupuncture. The MCI group showed stronger activity in the right supramarginal gyrus after acupuncture treatment compared to healthy controls. Meta-regression analysis showed that the right anterior thalamic projection ReHo index was significantly correlated with the MMSE score after acupuncture treatment in all MCI patients. Conclusions: Acupuncture therapy has a modulating effect on the brain regions of MCI patients. However, due to the inadequate experimental design of neuroimaging studies, multi-center neuroimaging studies with large samples are needed better to understand the potential neuroimaging mechanisms of acupuncture for MCI. In addition, machine learning algorithm-based predictive models for evaluating the efficacy of acupuncture for MCI may become a focus of future research. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022287826, identifier: CRD 42022287826.