Effects of traditional Chinese medicine-assisted intervention on improving postpartum lactation: A systematic review and meta-analysis.

Importance: Breast milk is the safest food for infants and has many psychological and physical benefits for infants and mothers. However, problems encountered during the breastfeeding process can reduce postpartum women's willingness to breastfeed. Lactation and engorgement may be improved through Traditional Chinese Medicine auxiliary therapy. However, the overall efficacy of various Traditional Chinese Medicine auxiliary therapies and the relevant meridians and acupuncture points for treating breast milk deficiency remain unclear. Objective: To investigate Traditional Chinese Medicine auxiliary therapy's effectiveness and acupoints for postpartum women who experience problems during the breastfeeding process. Methods: Data were sourced from Embase, Web of Science, CINAHL, Cochrane, CNKI, PubMed, and the Airiti Library Central Register of Controlled Trials and Clinical Trials from the database inception to October 2022. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Main outcome measures: The primary outcomes were overall efficiency, prolactin level, milk volume, and breast engorgement in postpartum women with lactation deficiency after-assisted therapies and the correlation between meridian points and milk secretion. Results: A total of 1,516 studies were initially identified, and 357 articles were assessed. In the final analysis, 20 studies were included, covering various Traditional Chinese Medicine therapies (acupuncture, acupressure, scrapping, moxibustion cupping, etc.) to stimulate relative acupoints without any acupoint stimulation. The overall efficiency (odds ratio [OR] = 14.17, 95% confidence interval [CI] = 6.49 to 30.92), prolactin level (standardized mean difference [SMD] = 0.36, 95% CI = 0.074 to 0.64), improvement of milk volume (SMD = 0.94, 95% CI = 0.59 to 1.29), reduction of engorgement level (OR= 18, 95% CI = 8.34 to 38.82) demonstrated that Traditional Chinese Medicine therapies can effectively improve lactation and breast fullness, thereby helping patients with breast milk deficiency. The most common acupuncture points used to treat agalactia were classified as the Stomach Meridian, Small Intestine Meridian, and Conception Vessel, with the common acupoints CV17: Danzhong, ST18: Rugen, SI1: Shaoze, ST36: Zusanli, and ST16: Yingchuang. Conclusion: Adjuvant Traditional Chinese Medicine therapy can improve lactation and breast engorgement, thereby increasing the willingness to breastfeed. Clinical Finding: 1. The best time for Traditional Chinese Medicine acupoint intervention for breast deficiency treatment is within 24 h 2. The most effective acupuncture points for improving milk deficiency and bloating pain are ST18: Rugen, ST16: Yingchuang, ST36: Zusanli, SI1: Shaoze, CV17: Danzhong. 3. Traditional Chinese Medicine is non-invasive and effective techniques such as scraping, cupping, acupressure and ear peas. 4. Traditional Chinese Medicine can be combined with other different acupuncture points according to the different constitutions of post-partum women. Breast acupressure, ear acupuncture, scrapping, cupping, and moxibustion are noninvasive treatments that can effectively help patients during lactation, and their clinical practice should be considered and widely promoted.

Arenobufagin inhibits lung metastasis of colorectal cancer by targeting c-MYC/Nrf2 axis.

BACKGROUND: Colorectal cancer (CRC) is one of the commonest cancers worldwide. Metastasis is the most common cause of death in patients with CRC. Arenobufagin is an active component of bufadienolides, extracted from toad skin and parotid venom. Arenobufagin reportedly inhibits epithelial-to-mesenchymal transition (EMT) and metastasis in various cancers. However, the mechanism through which arenobufagin inhibits CRC metastasis remains unclear. PURPOSE: This study aimed to elucidate the molecular mechanisms by which arenobufagin inhibits CRC metastasis. METHODS: Wound-healing and transwell assays were used to assess the migration and invasion of CRC cells. The expression of nuclear factor erythroid-2-related factor 2 (Nrf2) in the CRC tissues was assessed using immunohistochemistry. The protein expression levels of c-MYC and Nrf2 were detected by immunoblotting. A mouse model of lung metastasis was used to study the effects of arenobufagin on CRC lung metastasis in vivo. RESULTS: Arenobufagin observably inhibited the migration and invasion of CRC cells by downregulating c-MYC and inactivating the Nrf2 signaling pathway. Pretreatment with the Nrf2 inhibitor brusatol markedly enhanced arenobufagin-mediated inhibition of migration and invasion, whereas pretreatment with the Nrf2 agonist tert­butylhydroquinone significantly attenuated arenobufagin-mediated inhibition of migration and invasion of CRC cells. Furthermore, Nrf2 knockdown with short hairpin RNA enhanced the arenobufagin-induced inhibition of the migration and invasion of CRC cells. Importantly, c-MYC acts as an upstream modulator of Nrf2 in CRC cells. c-MYC knockdown markedly enhanced arenobufagin-mediated inhibition of the Nrf2 signaling pathway, cell migration, and invasion. Arenobufagin inhibited CRC lung metastasis in vivo. Together, these findings provide evidence that interruption of the c-MYC/Nrf2 signaling pathway is crucial for arenobufagin-inhibited cell metastasis in CRC. CONCLUSIONS: Collectively, our findings show that arenobufagin could be used as a potential anticancer agent against CRC metastasis. The arenobufagin-targeted c-MYC/Nrf2 signaling pathway may be a novel chemotherapeutic strategy for treating CRC.

Rapid preparation and proton NMR fingerprinting of polysaccharides from Radix Astragali.

The purity, content, and structure of the polysaccharides prepared from a specific medicinal plant are the fundamental basis to interpret the observed biological activities. An ultrafiltration-based method has been developed for rapid preparation of total and fractional polysaccharides from Radix Astragali in high yield and purity. This method involves extraction of plant material by hot water, treatment with Sevag reagent, and ultrafiltration using molecular weight cutoff concentrators. The prepared polysaccharides were assessed by 1H NMR spectroscopy, providing general purity, fingerprinting, and structural information. This method may be used to efficiently screen polysaccharides in plants.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

Identification and Functional Characterization of Oxidosqualene Cyclases from Medicinal Plant Hoodia gordonii.

Oxidosqualene cyclases (OSCs) are the key enzymes accountable for the cyclization of 2,3-oxidosqualene to varied triterpenoids and phytosterols. Hoodia gordonii (from the family Apocynaceae), a native of the Kalahari deserts of South Africa, Namibia, and Botswana, is being sold as a prevalent herbal supplement for weight loss. The appetite suppressant properties are attributed to P57AS3, an oxypregnane steroidal glycoside. At the molecular level, the enzymes involved in the biosynthesis of triterpenes and phytosterols from H. gordonii have not been previously reported. In the current study, predicted transcripts potentially encoding oxidosqualene cyclases were recognized first by searching publicly available H. gordonii RNA-seq datasets. Two OSC-like sequences were selected for functional analysis. A monofunctional OSC, designated HgOSC1 which encodes lupeol synthase, and HgOSC2, a multifunctional cycloartenol synthase forming cycloartenol and other products, were observed through recombinant enzyme studies. These studies revealed that distinct OSCs exist for triterpene formation in H. gordonii and provided opportunities for the metabolic engineering of specific precursors in producing phytosterols in this plant species.

Causal association between tea consumption and head and neck cancer: a Mendelian randomization study.

Although evidence supports an observational association between tea consumption and susceptibility to head and neck cancer, the causal nature of this association remains unclear. We performed a two-sample Mendelian randomization (MR) analysis to determine the causal effects of tea consumption on head and neck cancer. We employed a fixed-effects inverse variance-weighted model for the MR analysis. Genome-wide association study (GWAS) summary data for tea consumption were obtained from the UK Biobank Consortium, and GWAS data for head and neck cancer were derived from two data sources and were used as the outcomes. Our MR analysis revealed limited evidence for a causal relationship between various types of tea intake and head and neck cancer. After adjustment for smoking and alcohol consumption, there was no causal relationship between tea consumption and head and neck cancer. Further experimental studies are required to confirm its potential role in these malignancies.

Recent advances in Platycodon grandiflorum polysaccharides: Preparation techniques, structural features, and bioactivities.

Platycodon grandiflorum, a globally recognized medicinal and edible plant, possesses significant nutritional value and pharmacological value. In traditional Chinese medicine, it has the effects of tonifying the spleen and replenishing the Qi, moistening the lung and relieving the cough, clearing the heat and detoxifying, and relieving the pain. Accumulating evidence has revealed that the polysaccharides from P. grandiflorum (PGPs) are one of the major and representative biologically active macromolecules and have diverse biological activities, such as immunomodulatory activity, anti-inflammatory activity, anti-tumor activity, regulation of the gut microbiota, anti-oxidant activity, anti-apoptosis activity, anti-angiogenesis activity, hypoglycemic activity, anti-microbial activity, and so on. Although the polysaccharides extracted from P. grandiflorum have been extensively studied for the extraction and purification methods, structural characteristics, and pharmacological activities, the knowledge of their structures and bioactivity relationship, toxicologic effects, and pharmacokinetic profile is limited. The main purpose of the present review is to provide comprehensively and systematically reorganized information on extraction and purification, structure characterizations, and biological functions as well as toxicities of PGPs to support their therapeutic potentials and sanitarian functions. New valuable insights for future research regarding PGPs were also proposed in the fields of therapeutic agents and functional foods.

Treatment of postpartum depression with integrated traditional Chinese and Western medicine nursing and electrical stimulation.

BACKGROUND: Postpartum depression (PPD) is a common psychological disease among puerperal women, and postpartum pelvic floor dysfunction is a common disease among pregnant women. The occurrence of postpartum pelvic floor dysfunction will increase the incidence of PPD. AIM: To explore the therapeutic effect of integrated traditional Chinese and Western medicine nursing combined with electrical stimulation of pelvic floor muscles and the rectus abdominis on PPD. METHODS: From April 2020 to January 2022, 100 parturients with a rectus abdominis muscle separation distance > 2.0 cm who underwent reexamination 6 wk after delivery at our hospital were selected as the research subjects. According to the random number table method, the patients were divided into either an observation group (n = 50) or a control group (n = 50). There was no significant difference in the general data between the two groups (P > 0.05). Both groups were treated by electrical stimulation. The observation group was additionally treated by integrated traditional Chinese and Western medicine nursing. A self-designed Depression Knowledge Questionnaire was used to evaluate the awareness of knowledge on depression in all patients 3 wk after intervention. The Hamilton Depression Scale (HAMD) was used to evaluate the depression before intervention and 1 wk and 3 wk after intervention, and the Morisky Medication Adherence Scale (MMAS-8) was used to evaluate the medication compliance. SPSS19.0 was used for statistical analyses. RESULTS: The rate of awareness of knowledge on depression in the observation group was significantly higher than that of the control group (P < 0.05). The scores of MMAS-8 were comparable between the two groups before intervention (P > 0.05), but were significantly higher in the observation group than in the control group at 1 wk and 3 wk after intervention (P < 0.05). The HAMD scores were comparable between the two groups before intervention (P > 0.05), but were significantly lower in the observation group than in the control group at 1 wk and 3 wk after intervention (P < 0.05). CONCLUSION: Integrated traditional Chinese and Western medicine nursing combined with electrical stimulation of pelvic floor muscles and the rectus abdominis is effective in the treatment of postpartum depression and worthy of clinical promotion.

[Screening of quality markers and activity verification of Glycyrrhizae Radix et Rhizoma based on small molecule compound-protein interaction].

In order to solve the problem of weak correlation between quality control components and efficacy of Glycyrrhizae Radix et Rhizoma, this study detected the interaction between small molecular chemical components of Glycyrrhizae Radix et Rhizoma and total proteins of various organs of mice by fluorescence quenching method to screen potential active components. The 27 chemical components in Glycyrrhizae Radix et Rhizoma were detected by HPLC and their deletion rates in 34 batches of Glycyrrhizae Radix et Rhizoma were calculated. Combined with the principle of component effectiveness and measurability, the potential quality markers(Q-markers) of Glycyrrhizae Radix et Rhizoma were screened. RAW264.7 macrophage injury model was induced by microplastics. The cell viability and nitric oxide content were detected by CCK-8 and Griess methods. The levels of inflammatory factors(TNF-α, IL-1ß, IL-6, CRP) and oxidative stress markers(SOD, MDA, GSH) were detected by the ELISA method to verify the activity of Q-markers. It was found that the interaction strength between different chemical components and organ proteins in Glycyrrhizae Radix et Rhizoma was different, reflecting different organ selectivity and 18 active components were screened out. Combined with the signal-to-noise ratio of the HPLC chromatographic peaks and between-run stability of the components, seven chemical components such as liquiritin apioside, liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, isoliquiritigenin and ammonium glycyrrhizinate were finally screened as potential Q-markers of Glycyrrhizae Radix et Rhizoma. In vitro experiments showed that Q-markers of Glycyrrhizae Radix et Rhizoma could dose-dependently alleviate RAW264.7 cell damage induced by microplastics, inhibit the secretion of inflammatory factors, and reduce oxidative stress. Under the same total dose, the combination of various chemical components could synergistically enhance anti-inflammatory and antioxidant effects compared with the single use. This study identified Q-markers related to the anti-inflammatory and antioxidant effects of Glycyrrhizae Radix et Rhizoma, which can provide a reference for improving the quality control standards of Glycyrrhizae Radix et Rhizoma.

The Cardiorenal Effects of Piper amalago Are Mediated by the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway and the Voltage-Dependent Potassium Channels.

Piper amalago L. is used in Brazilian traditional medicine to treat inflammation, chest pain, and anxiety. This study aimed to investigate the safety and the renal and cardiovascular effects of the volatile oil (VO) and the aqueous (AE) and hydroalcoholic (HE) extracts from P. amalago. The gas chromatography-mass spectrometry analyses identified 47 compounds in the VO, with ß-cyclogermacrene, spathulenol, ß-phellandrene, and α-pinene standing out. Among the 47 compounds also found in AE and HE by liquid chromatography-mass spectrometry, glycosylated flavones, organic acids, amino acids, and amides were highlighted. Some examples of these compounds are methoxy-methylenedioxy cis-cinnamoyl pyrrolidine, methoxy-methylenedioxy trans-cinnamoyl pyrrolidine, and cyclobutene-2,4-bis-(1,3-benzodioxol-5-methoxy-6-yl)-1,3-dicarboxapyrrolidide. The acute toxicity experiments were conducted on female rats (n = 5). The cardiorenal assays (n = 8) and evaluations of vasodilatory effects on the mesenteric vascular bed (n = 5) were conducted on male rats. In either extract or VO, there were no mortality or changes in relative weights or histopathological analysis of the organs. Urinary volume and renal electrolyte excretion were elevated significantly during repeated dose 7-day treatment with different preparations from P. amalago. None of the preparations induced hypotension or changes in cardiac electrical activity. Only HE promoted significant vasodilatory effects in rats' isolated mesenteric vascular beds. These effects were completely abolished in the presence of L-NAME plus 4-aminopyridine. Therefore, P. amalago leaves are safe and present diuretic activity after acute and repeated dose administration over 7 days. Moreover, the HE induced significant vasodilator response in rats' mesenteric vascular beds by NO/cGMP pathway and voltage-dependent K+ channels activation.

Effects of total flavones of Abelmoschus manihot (L.) on the treatment of diabetic nephropathy via the activation of solute carriers in renal tubular epithelial cells.

As a traditional Chinese medicine, Huangkui capsule (HKC) has been used to treat patients with kidney diseases, including diabetic nephropathy (DN). We have recently demonstrated that HKC could re-regulate the activities of solute carriers (SLC)s in proximal and distal convoluted tubules of kidneys in regression of the development of DN. The main active chemical constituents of HKC are the flavones of Abelmoschus manihot (L.). The current study aims to further evaluate the efficacy of total flavones of A. manihot (TFA) in the regression of DN by analyzing SLC activities in proximal and distal convoluted tubules of kidneys. TFA (0.076 g/kg/d) or vehicle was administered in db/db mice, the animal model of type 2 diabetes and DN, daily via oral gavage for four weeks. Blood glucose levels and urinary albumin-to-creatinine ratio (UACR) were measured and used for the determination of T2D and DN. Ten SLCs, including slc2a2, slc4A1, slc5a2, slc5A3, slc5a8, slc6a20, slc27a2, slc12a3, slc34a1 and slc38a2 were highly expressed in proximal and distinct convoluted tubules of kidneys. Their expression at mRNA and protein levels before and after TFA treatment were analyzed with real-time RT-PCR and immunohistochemistry. Data showed that UACR in the db/db mice after TFA treatment was significantly decreased. Compared with the group of non-diabetic control, slc2a2, slc4A1, slc5a2, slc5A3, slc5a8, slc6a20, slc27a2, slc12a3, slc34a1 and slc38a2 in the group of DN were down-regulated but up-regulated after TFA treatment. Further analyses of whole kidney sections indicated that the numbers and structures of the nephron in db/db mice was increased and improved after TFA treatment. Thereby, the current study provides further evidence that the flavones in A. manihot have pharmacological effects on the treatment of DN by improving the biological function of SLCs in kidneys.

[Quality status of Bombyx Batryticatus and suggestions for Chinese Pharmacopoeia (2025)].

To understand the current quality status and rearing situation of Bombyx Batryticatus, the authors collected 102 batches of Bombyx Batryticatus from different main producing areas and five major Chinese medicine markets from 2016 to 2018, and measured the properties and quality of the silk gland, to clarify the quality status of Bombyx Batryticatus from different producing areas and markets. In addition, 35 batches of Bombyx Batryticatus from 2019 to 2022 were used to verify the silk gland after revision. Moreover, Beauveria Bassiana was inoculated in the silkworm of 4-5 instars, and standardized rearing was carried out until they die. The death rate and the quality of Bombyx Batryticatus were measured to determine the differences in Bombyx Batryticatus of different instars, and explore the rationality of the infection age of Bombyx Batryticatus in Chinese Pharmacopoeia(2020). The results revealed that in the 102 batches of Bombyx Batryticatus, the qualification rate of silk gland was low; the content of total ash far exceeded the standard; the content of beauvericin varied greatly. The qualification rate of the silk gland of the 35 batches of Bombyx Batryticatus was only 47.49%, which could be increased to 73.00% if the number of silk gland was 2 to 4. The death rate of Bombyx Batryticatus at different infection ages was quite different, with uneven quality. Generally, the yield of Bombyx Batryticatus inoculated on the first day of the fifth instar was high with good quality. Therefore, in combination with the quality and actual production of Bombyx Batryticatus, the following suggestions were proposed for revision of Bombyx Batryticatus in Chinese Pharmacopoeia(2025): The number of silk gland should be revised as 2-4 bright brown or bright black silk glands, after which, the quality of Bombyx Batryticatus could be guaranteed, and the "quality identification based on character" could also be reflected scientifically; the content determination index that the content of beauvericin shall not be less than 0.017% should be added to better control the quality of Bombyx Batryticatus; the infection age should be revised as the first day of the fifth instar to narrow the age span, which could better fit the actual production and ensure the quality of Bombyx Batryticatus.

[Effects and mechanisms of total flavones of Abelmoschus manihot in inhibiting podocyte necroptosis and renal fibrosis in diabetic kidney disease].

Previous studies have shown that high blood glucose-induced chronic microinflammation can cause inflammatory podocyte injury in patients with diabetic kidney disease(DKD). Therein, necroptosis is a new form of podocyte death that is closely associated with renal fibrosis(RF). To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese herbal medicine Abelmoschus manihot for treating kidney diseases, on podocyte necroptosis and RF in DKD, and to further reveal its scientific connotation with multi-pathway and multi-target, the authors randomly divided all rats into four groups: a namely normal group, a model group, a TFA group and a rapamycin(RAP) group. After the modified DKD rat models were successfully established, four group rats were given double-distilled water, TFA suspension and RAP suspension, respectively by gavage every day. At the end of the 4th week of drug treatment, all rats were sacrificed, and the samples of their urine, blood and kidneys were collected. And then, the various indicators related to podocyte necroptosis and RF in the DKD model rats were observed, detected and analyzed, respectively. The results indicated that, general condition, body weight(BW), serum creatinine(Scr), urinary albumin(UAlb), and kidney hypertrophy index(KHI) in these modified DKD model rats were both improved by TFA and RAP. Indicators of RF, including glomerular histomorphological characteristics, fibronectin(FN) and collagen type Ⅰ(collagen Ⅰ) staining extent in glomeruli, as well as the protein expression levels of FN, collagen Ⅰ, transforming growth factor-ß1(TGF-ß1) and Smad2/3 in the kidneys were improved respectively by TFA and RAP. Podocyte damage, including foot process form and the protein expression levels of podocin and CD2AP in the kidneys was improved by TFA and RAP. In addition, tumor necrosis factor-α(TNF-α)-mediated podocyte necroptosis in the kidneys, including the morphological characteristics of podocyte necroptosis, the extent and levels of the protein expression of TNF-α and phosphorylated mixed lineage kinase domain like pseudokinase(p-MLKL) was improved respectively by TFA and RAP. Among them, RAP had the better effect on p-MLKL. More importantly, the activation of the receptor interacting serine/threonine protein kinase 1(RIPK1)/RIPK3/MLKL signaling axis in the kidneys, including the expression levels of its key signaling molecules, such as phosphorylated receptor interacting serine/threonine protein kinase 1(p-RIPK1), p-RIPK3, p-MLKL and cysteinyl aspartate specific proteinase-8(caspase-8) was improved respectively by TFA and RAP. Among them, the effect of TFA on p-RIPK1 was superior. On the whole, in this study, the authors demonstrated that TFA alleviates podocyte necroptosis and RF in DKD through inhibiting the activation of the TNF-α-mediated RIPK1/RIPK3/MLKL signaling axis in diabetic kidneys. The authors' findings provide new pharmacological evidence to reveal the scientific connotation of TFA in treating RF in DKD in more depth.

Evaluation of the efficacy of Abelmoschus manihot (L.) on diabetic nephropathy by analyzing biomarkers in the glomeruli and proximal and distal convoluted tubules of the kidneys.

Introduction: As a traditional Chinese medicine, Abelmoschus manihot (L.) in the form of Huangkui (HK) capsule has been used as a medication for kidney diseases, including diabetic nephropathy (DN), in China. The most significant effect of HK capsule treatment in kidney diseases is the reduction of albuminuria and proteinuria. To evaluate the efficacy of HK capsule in the regression of DN, in the current study, we analyzed the biomarkers in the glomerulus and proximal and distal convoluted tubules in the kidneys of db/db mice, the animal model for type 2 diabetes and DN. Methods: Huangkui capsules (0.84 g/kg/d) or vehicle were administered daily via oral gavage for 4 weeks in db/db mice. Urinary albumin-to-creatinine ratio and blood glucose levels were measured during the whole experimental period. Five biomarkers in the glomerulus and proximal and distal convoluted tubules in the kidneys were selected, namely, col4a3, slc5a2, slc34a1, slc12a3, and slc4a1, and their activities at mRNA and protein levels before and after HK capsule treatment were analyzed by real-time RT-PCR and immunohistochemistry. Result and discussion: After HK capsule treatment for 4 weeks, the urinary albumin-to-creatinine ratio in db/db mice was found to be significantly decreased. The activities of col4a3, slc5a2, slc34a1, slc12a3, and slc4a1 in the kidneys were upregulated in db/db mice prior to the treatment but downregulated after HK capsule treatment. Further analyses of the fields of whole kidney tissue sections demonstrated that the number of nephrons in the kidneys of db/db mice with HK capsule treatment was higher than that in the kidneys of db/db mice without HK capsule treatment. Thereby, the current study provides experimental evidence confirming the medical efficacy of A. manihot in the reduction of albuminuria and proteinuria, suggesting that A. manihot may have pharmacological efficacy in the regression of the development of type 2 diabetes-DN.

Chemical Profiles and Cytotoxic Activities of Essential Oils from Six Species of Baccharis Subgenus Coridifoliae (Asteraceae).

Several Baccharis species are popularly known in traditional medicine as "carquejas", "vassouras", "ervas-santas" and "mio-mios", and are used as anti-inflammatories, digestives, and diuretics. This study aimed to investigate the chemical compositions and cytotoxic activities of essential oils (EOs) of six Baccharis species belonging to subgenus Coridifoliae, namely B. albilanosa, B. coridifolia, B. erigeroides, B. napaea, B. ochracea, and B. pluricapitulata. GC/MS analyses of the EOs showed that the oxygenated sesquiterpenes spathulenol (7.32-38.22 %) and caryophyllene oxide (10.83-16.75 %) were the major components for all the species. The EOs of almost all species were cytotoxic against cancer (BT-549, KB, SK-MEL and SK-OV-3) and normal kidney (VERO and LLC-PK1) cell lines, whereas B. erigeroides EO showed cytotoxicity only against LLC-PK1. This article augments the current knowledge about the chemical-biological properties of Baccharis subgenus Coridifoliae and discusses the therapeutic potentials of these economically unexploited plants.

Facile and green fabrication of tumor- and mitochondria-targeted AIEgen-protein nanoparticles for imaging-guided photodynamic cancer therapy.

In recent years, aggregation-induced emission (AIE)-active materials have been emerging as a promising means for bioimaging and phototherapy. However, the majority of AIE luminogens (AIEgens) need to be encapsulated into versatile nanocomposites to improve their biocompatibility and tumor targeting. Herein, we prepared a tumor- and mitochondria-targeted protein nanocage by the fusion of human H-chain ferritin (HFtn) with a tumor homing and penetrating peptide LinTT1 using genetic engineering technology. The LinTT1-HFtn could serve as a nanocarrier to encapsulate AIEgens via a simple pH-driven disassembly/reassembly process, thereby fabricating the dual-targeting AIEgen-protein nanoparticles (NPs). The as designed NPs exhibited an improved hepatoblastoma-homing property and tumor penetrating ability, which is favorable for tumor-targeted fluorescence imaging. The NPs also presented a mitochondria-targeting ability, and efficiently generated reactive oxygen species (ROS) upon visible light irradiation, making them valuable for inducing efficient mitochondrial dysfunction and intrinsic apoptosis in cancer cells. In vivo experiments demonstrated that the NPs could provide the accurate tumor imaging and dramatic tumor growth inhibition with minimal side effects. Taken together, this study presents a facile and green approach for fabrication of tumor- and mitochondria-targeted AIEgen-protein NPs, which can serve as a promising strategy for imaging-guided photodynamic cancer therapy. STATEMENT OF SIGNIFICANCE: AIE luminogens (AIEgens) show strong fluorescence and enhanced ROS generation in the aggregate state, which would facilitate the image-guided photodynamic therapy [12-14]. However, the major obstacles that hinder biological applications are their lack of hydrophilicity and selective targeting [15]. To address this issue, this study presents a facile and green approach for the fabrication of tumor­ and mitochondria­targeted AIEgen-protein nanoparticles via a simple disassembly/reassembly of the LinTT1 peptide-functionalized ferritin nanocage without any harmful chemicals or chemical modification. The targeting peptide-functionalized nanocage not only restricts the intramolecular motion of AIEgens leading to enhanced fluorescence and ROS production, but also confers good targeting to AIEgens.

6-Oxofurostane and (iso)Spirostane Types of Saponins in Smilax sieboldii: UHPLC-QToF-MS/MS and GNPS-Molecular Networking Approach for the Rapid Dereplication and Biodistribution of Specialized Metabolites.

Identifying novel phytochemical secondary metabolites following classical pharmacognostic investigations is tedious and often involves repetitive chromatographic efforts. During the past decade, Ultra-High Performance Liquid Chromatography-Quadrupole Time of Flight-Tandem Mass Spectrometry (UHPLC-QToF-MS/MS), in combination with molecular networking, has been successfully demonstrated for the rapid dereplication of novel natural products in complex mixtures. As a logical application of such innovative tools in botanical research, more than 40 unique 3-oxy-, 3, 6-dioxy-, and 3, 6, 27-trioxy-steroidal saponins were identified in aerial parts and rhizomes of botanically verified Smilax sieboldii. Tandem mass diagnostic fragmentation patterns of aglycones, diosgenin, sarsasapogenin/tigogenin, or laxogenin were critical to establishing the unique nodes belonging to six groups of nineteen unknown steroidal saponins identified in S. sieboldii. Mass fragmentation analysis resulted in the identification of 6-hydroxy sapogenins, believed to be key precursors in the biogenesis of characteristic smilaxins and sieboldins, along with other saponins identified within S. sieboldii. These analytes' relative biodistribution and characteristic molecular networking profiles were established by analyzing the leaf, stem, and root/rhizome of S. sieboldii. Deducing such profiles is anticipated to aid the overall product integrity of botanical dietary supplements while avoiding tedious pharmacognostic investigations and helping identify exogenous components within the finished products.

[Regularity of meridian-acupoint reactions of foot three yin meridians in primary dysmenorrhea and secondary dysmenorrhea patients].

OBJECTIVE: To observe the meridian-acupoint reactions of foot three yin meridians in primary dysmenorrhea(PD) and secondary dysmenorrhea(SD) patients, so as to summarize the rules of meridian-acupoint reaction and acupoints selection. METHODS: Thirty-five patients with PD (PD group), 34 patients with SD (SD group) and 35 healthy subjects (healthy group) were recruited. The compression method was used to examine the lower leg segment of the foot three yin meridians. Positive reactions(palpable skin changes, including cords, nodules, depressions) and tenderness of meridians and acupoints were recorded. The visual analogue scale (VAS) was used to evaluate the tenderness severity of acupoints. RESULTS: Compared with the healthy group, the probability of positive reactions and tenderness in foot three yin meridians were higher in PD and SD groups (P<0.01,P<0.05). Compared with the PD group, the probability of positive reactions in Spleen and Liver Meridians were higher in the SD group, with higher probability of tenderness in Liver Meridian(P<0.05). The probability of positive reactions and tenderness in the Spleen Meridian of PD and SD groups was significantly higher than that in the Kidney Meridian (P<0.01), while the probability of tenderness in the Spleen Meridian of the PD group was significantly higher than that in the Liver Meridian (P<0.05). Positive reactions and tenderness were concentrated at Yinlingquan (SP9), Diji (SP8) and Sanyinjiao (SP6) of Spleen Meridian and Xiguan (LR7) and Ligou (LR5) in Liver Meridian of PD and SD groups. In comparison with the PD group, the probability of positive reactions, tenderness and VAS score of SP8 and LR5 of the SD group were higher (P<0.05, P<0.01). CONCLUSION: The positive reaction occurs most frequently in the Spleen Meridian, followed by the Liver Meridian, and least frequently in the Kidney Meridian. The acupoints with positive reaction are different between PD and SD, which suggests that the Spleen Meridian acupoints should be the main acupoints when treating the two kinds of dysmenorrhea, and acupoints should also be selected according to the meridian and acupoint examination results.

Examining Soft and Hard Attributes of Health Care Service Quality and Their Impacts on Patient Satisfaction and Loyalty.

BACKGROUND AND OBJECTIVES: Many studies have confirmed the influences of various service quality dimensions on patient satisfaction and loyalty, but no existing theoretical model accounts for variation in how different types of patients evaluate service quality's soft and hard attributes. This research gap may cause problems for administrators needing to decide how to distribute resources appropriately across multiple departments. Therefore, this study establishes a theoretical model of the differences between inpatients' and outpatients' evaluations of hard and soft qualities and compares such evaluations' influences on patient satisfaction and loyalty. Also, to supplement statistical analysis and respond to scholars' calls for more mixed-methods studies of health care quality, this research incorporates analysis of online reviews to provide a holistic, close to real-time picture of patients' service experience perceptions. METHODS: This study's survey sample comprised 292 inpatients and 137 outpatients from a Taiwanese hospital. We used partial least squares structural equation modeling to test the hypothetical model and importance-performance map analysis to identify factors that were significant to the service process but performed poorly. Finally, we used a text-mining technique to scrape 536 reviews posted on Google Maps, and Leximancer Portal to perform automated content and sentiment analyses on those data, as a means of mapping the critical concepts and themes that influenced patient experiences. RESULTS: This study's analyses support the ideas that both hard and soft qualities are critical dimensions of service quality, and that each has different influences on inpatients' and outpatients' satisfaction and loyalty. Specifically, the sampled inpatients strongly valued the hard qualities of the hospital but were not satisfied with it. On the other hand, soft qualities attracted outpatients' attention and influenced their satisfaction and loyalty. In addition, content analysis revealed that soft qualities were the main reason patients left comments, whether positive or negative. Waiting time emerged as another critical element in triggering patients' unfavorable reviews. CONCLUSIONS: Patient population type, whether inpatient or outpatient, has been found to impact perceptions of service quality within health care institutions. As such, health care administrators should be cognizant of this phenomenon and make informed and tailored decisions when addressing quality within their respective services. Emphasis on the development of both interpersonal and professional skills among health care personnel may prove beneficial in enhancing the patient experience and ultimately fostering positive online reviews.

The therapeutic effect of wasp venom (Vespa magnifica, Smith) and its effective part on rheumatoid arthritis fibroblast-like synoviocytes through modulating inflammation, redox homeostasis and ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is related to the aberrant proliferation of fibroblast-like synoviocytes (FLS). Wasp venom (WV, Vespa magnifica, Smith), an insect secretion, has been used to treat RA in Chinese Jingpo national minority's ancient prescription. However, the potential mechanisms haven't been clarified. AIM OF THE STUDY: The purposes of this paper were two-fold. First, to investigate which was the best anti-RA effective part of WV-I (molecular weight less than 3 kDa), WV-II (molecular weight 3-10 kDa) and WV-III (molecular weight more than 10 kDa) that were separated from WV. Second, to explore the underlying molecular mechanism of WV and WV-II that was best effective part in RA. MATERIALS AND METHODS: The wasps were electrically stimulated and the secretions were collected. WV-I, WV-II and WV-III were acquired by ultracentrifuge method according to molecular weight. Next, WV, WV-I, WV-II and WV-III were identified by HPLC. Functional annotation and pathway analysis of WV used to bioinformatics analysis. RNA-seq analyses were constructed to identify differentially expressed genes (DEGs). GO and KEGG pathway analyses were performed by Metascape database. STRING was used to analyze the PPI network from DEGs. Next, PPI network was visualized using Cytoscape that based on MCODE. The pivotal genes of PPI network and MCODE analysis were verified by qRT-PCR. Subsequently, MH7A cells were performed by MTT assay to evaluate the ability of inhibiting cell proliferation. Luciferase activity assay was conducted in HepG2/STAT1 or HepG2/STAT3 cells to assess STAT1/3 sensitivity of WV, WV-I, WV-II and WV-III. Additionally, interleukin (IL)-1ß and IL-6 expression levels were detected by ELISA kits. Intracellular thioredoxin reductase (TrxR) enzyme was evaluated by TrxR activity assay kit. ROS levels, lipid ROS levels and Mitochondrial membrane potential (MMP) were assessed by fluorescence probe. Cell apoptosis and MMP were measured by using flow cytometry. Furthermore, the key proteins of JAK/STAT signaling pathway, protein levels of TrxR and glutathione peroxidase 4 axis (GPX4) were examined by Western blotting assay. RESULTS: RNA-sequencing analysis of WV displayed be related to oxidation-reduction, inflammation and apoptosis. The data displayed that WV, WV-II and WV-III inhibited significantly cells proliferation in human MH7A cell line compared to WV-I treatment group, but WV-III had no significant suppressive effect on luciferase activity of STAT3 compared with IL-6-induced group. Combined with earlier reports that WV-III contained major allergens, we selected WV and WV-II further to study the mechanism of anti-RA. In addition, WV and WV-II decreased the level of IL-1ß and IL-6 in TNF-α-induced MH7A cells via inactivating of JAK/STAT signaling pathway. On the other hand, WV and WV-II down-regulated the TrxR activity to produce ROS and induce cell apoptosis. Furthermore, WV and WV-II could accumulate lipid ROS to induce GPX4-mediated ferroptosis. CONCLUSIONS: Taken together, the experimental results revealed that WV and WV-II were potential therapeutic agents for RA through modulating JAK/STAT signaling pathways, redox homeostasis and ferroptosis in MH7A cells. Of note, WV-II was an effective part and the predominant active monomer in WV-II will be further explored in the future.