Shen Qi Wan ameliorates nephritis in chronic kidney disease via AQP1 and DEFB1 regulation.

Shen Qi Wan (SQW) has been proven to exert anti-inflammatory effects in the kidneys of CKD models accompanied by unclear therapeutic mechanisms. This study aims to evaluate the kidney-protective and anti-inflammatory effects of SQW and to elucidate its fundamental mechanisms for CKD treatment. Firstly, the main active components of SQW were identified by UPLC-Q-TOF/MS technique. Subsequently, we evaluated inflammatory factors, renal function and renal pathology changes following SQW treatment utilizing adenine-induced CKD mice and aquaporin 1 knockout (AQP1-/-) mice. Additionally, we conducted RNA-seq analysis and bioinformatics analysis to predict the SQW potential therapeutic targets and anti-nephritis pathways. Simultaneously, WGCNA analysis method and machine learning algorithms were used to perform a clinical prognostic analysis of potential biomarkers in CKD patients from the GEO database and validated through clinical samples. Lipopolysaccharide-induced HK-2 cells were further used to explore the mechanism. We found that renal collagen deposition was reduced, serum inflammatory cytokine levels decreased, and renal function was improved after SQW intervention. It can be inferred that ß-defensin 1 (DEFB1) may be a pivotal target, as confirmed by serum and renal tissue samples from CKD patients. Furthermore, SQW assuages inflammatory responses by fostering AQP1-mediated DEFB1 expression was confirmed in in vitro and in vivo studies. Significantly, the renal-protective effect of SQW is to some extent attenuated after AQP1 gene knockout. SQW could reduce inflammatory responses by modulating AQP1 and DEFB1. These findings underscore the potential of SQW as a promising contender for novel prevention and treatment strategies within the ambit of CKD management.

Electroacupuncture at ST36 acupoint regulates stem cells during experimental autoimmune encephalomyelitis.

BACKGROUND: Electroacupuncture (EA) is given to assist in the treatment of MS, which is an effective therapeutic method. However, the therapy mechanism of EA related to stem cells in the treatment of MS is not yet known. In this study, we used a classic animal model of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE) to evaluate the therapeutic effect of EA at Zusanli (ST36) acupoint in EAE and shed light on its potential roles in the effects of stem cells in vivo. METHODS: The EAE animal models were established. From the first day after immunization, EAE model mice received EA at ST36 acupoint, named the EA group. The weight and clinical score of the three groups were recorded for 28 days. The demyelination, inflammatory cell infiltration, and markers of neural stem cells (NSCs), hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs) were compared. RESULTS: We showed that EAE mice treated with EA at ST36 acupoint, were suppressed in demyelination and inflammatory cell infiltration, and thus decreased clinical score and weight loss and mitigated the development of EAE when compared with the EAE group. Moreover, our data revealed that the proportions of NSCs, HSCs, and MSCs increased in the EA group compared with the EAE group. CONCLUSIONS: Our study suggested that EA at ST36 acupoint was an effective nonpharmacological therapeutic protocol that not only reduced the CNS demyelination and inflammatory cell infiltration in EAE disease but also increased the proportions of various stem cells. Further study is necessary to better understand how EA at the ST36 acupoint affects EAE.

Global proteome and lysine succinylation analyses provide insights into the secondary metabolism in Salvia miltiorrhiza.

Danshen, belongs to the Lamiaceae family, and its scientific name is Salvia miltiorrhiza Bunge. It is a valuable medicinal plant to prevent and treat cardiovascular and cerebrovascular diseases. Lysine succinylation, a widespread modification found in various organisms, plays a critical role in regulating secondary metabolism in plants. The hairy roots of Salvia miltiorrhiza were subject to proteomic analysis to identify lysine succinylation sites using affinity purification and HPLC-MS/MS in this investigation. Our findings reveal 566 lysine succinylation sites in 348 protein sequences. We observed 110 succinylated proteins related to secondary metabolism, totaling 210 modification sites. Our analysis identified 53 types of enzymes among the succinylated proteins, including phenylalanine ammonia-lyase (PAL) and aldehyde dehydrogenase (ALDH). PAL, a crucial enzyme involved in the biosynthesis of rosmarinic acid and flavonoids, displayed succinylation at two sites. ALDH, which participates in the phenylpropane metabolic pathway, was succinylated at 8 eight sites. These observations suggest that lysine succinylation may play a vital role in regulating the production of secondary metabolites in Salvia miltiorrhiza. Our study may provide valuable insights for further investigation on plant succinylation, specifically as a reference point. SIGNIFICANCE: Salvia miltiorrhiza Bunge is a valuable medicinal plant that prevents and treats cardiovascular and cerebrovascular diseases. Lysine succinylation plays a critical role in regulating secondary metabolism in plants. The hairy roots of Salvia miltiorrhiza were subject to proteomic analysis to identify lysine succinylation sites using affinity purification and HPLC-MS/MS in this investigation. These observations suggest that lysine succinylation may act as a vital role in regulating the production of secondary metabolites in Salvia miltiorrhiza. Our study may provide valuable insights for further investigation on succinylation in plants, specifically as a reference point.

Shen Qi Wan attenuates renal interstitial fibrosis through upregulating AQP1.

Renal interstitial fibrosis (RIF) is the crucial pathway in chronic kidney disease (CKD) leading to the end-stage renal failure. However, the underlying mechanism of Shen Qi Wan (SQW) on RIF is not fully understood. In the current study, we investigated the role of Aquaporin 1 (AQP1) in SQW on tubular epithelial-to-mesenchymal transition (EMT). A RIF mouse model induced by adenine and a TGF-ß1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo. Subsequently, the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown. The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine, increased the protein expression of E-cadherin and AQP1 expression, and decreased the expression of vimentin and α-smooth muscle actin (α-SMA). Similarly, treatmement with SQW-containing serum significantly halted EMT process in TGF-ß1 stimulated HK-2 cells. The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1. AQP1 knockdown also increased the mRNA expression of vimentin and α-SMA, and decreased the expression of E-cadherin. The protein expression of vimentin increased, while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells. These results revealed that AQP1 knockdown promoted EMT. Furthermore, AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells. In sum, SQW attentuates EMT process in RIF through upregulation of the expression of AQP1.

Molecular mechanisms and therapeutic potential of icariin in the treatment of Alzheimer's disease.

BACKGROUND: Icariin (ICA) is the main active component of Epimedium, a traditional Chinese medicine (TCM), known to enhance cognitive function in Alzheimer's disease (AD). This study aims to investigate and summarize the mechanisms through which ICA treats AD. METHODS: The PubMed and CNKI databases were utilized to review the advancements in ICA's role in AD prevention and treatment by analyzing literature published between January 2005 and April 2023. To further illustrate ICA's impact on AD development, tables, and images are included to summarize the relationships between various mechanisms. RESULTS: The study reveals that ICA ameliorates cognitive deficits in AD model mice by modulating Aß via multiple pathways, including BACE-1, NO/cGMP, Wnt/Ca2+, and PI3K/Akt signaling. ICA exhibits neuroprotective properties by inhibiting neuronal apoptosis through the suppression of ER stress in AD mice, potentially linked to NF-κB, MAPK, ERK, and PERK/Eif2α signaling pathways. Moreover, ICA may safeguard neurons by attenuating mitochondrial oxidative stress injury. ICA can also enhance learning, memory, and cognition by improving synaptic structure via regulation of the PSD-95 protein. Furthermore, ICA can mitigate neuroinflammation by inactivating microglial activity through the upregulation of PPARγ, TAK1/IKK/NF-κB, and JNK/p38 MAPK signaling pathways. CONCLUSION: This study indicates that ICA possesses multiple beneficial effects in AD treatment. Through the integration of pharmacological and molecular biological research, ICA may emerge as a promising candidate to expedite the advancement of TCM in the clinical management of AD.

Research on the effect of Dipsaci Radix before and after salt-processed on kidney yang deficiency syndrome rats and the preliminary mechanism study through the BMP-Smad signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dipsaci Radix (DR) is the dry root of Dipsacus asper Wall. ex DC. AIM OF THE STUDY: The purpose of this study was to compare the effects of DR on rats before and after salt-processed with kidney yang deficiency syndrome (KYDS), and we selected the BMP-Smad signaling pathway to explore the mechanism of DR. MATERIALS AND METHODS: The model of KYDS was established by subcutaneous injection of hydrocortisone, the crude DR (CDR) and salt-processed DR (SDR) were given the corresponding dose (2 g/kg, 4 g/kg, and 6 g/kg). The organ index and the contents of adrenocorticotropic hormone (ACTH), cortistatin (CORT), thyroid hormone (T4), tumor necrosis factor-alpha (TNF-α), testosterone (T), estradiol (E2), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), Na+-K+-ATPase, and growth hormone (GH) in serum were measured to evaluate the intervention effect of DR on KYDS rats. The expression of Smad 1, Smad 4, Smad 5, Smad 8, and BMP 7 protein in kidney was determined by immunohistochemistry, quantitative PCR (qPCR) and Western blot analysis. The effects of DR on 5 expression factors in the BMP-Smad signaling pathway were studied. Constituents absorbed into blood were identified by UPLC-Q-TOF/MS. RESULTS: The results showed that compared with the model group, the thymus and kidney index, as well as the contents of ACTH, CORT, cAMP, GH, Na+-K+-ATPase, T, T4, and E2 were significantly increased in the CDR and SDR groups, and the contents of cGMP and TNF-α were significantly decreased. Compared with the CDR high dose group, ACTH, Na+-K+-ATPase, T, and T4 were significantly increased in the SDR high dose group. The results of immunohistochemistry, qPCR, and Western blot analysis showed that compared with the model group, the expression levels of Smad 1, Smad 4, Smad 5, Smad 8 and BMP 7 proteins in the kidney of DR groups were significantly increased. And SDR groups tended to be better than CDR groups. 8 constituents migrating to blood were identified. CONCLUSION: This study showed that both CDR and SDR could have a good therapeutic effect on KYDS, and SDR was better than CDR. This study chose the BMP-Smad signaling pathway to study the mechanism of DR in the treatment of KYDS and provided a scientific basis for the processing mechanism of salt-processed.

Essential oil of Acorus tatarinowii Schott inhibits neuroinflammation by suppressing NLRP3 inflammasome activation in 3 × Tg-AD transgenic mice.

BACKGROUND: Shi chang pu (Acorus tatarinowii Schott) is a herbal used in the treatment of Alzheimer's disease (AD) in China. The essential oil of Shi chang pu (SCP-oil) is the main active component. However, its effects on the neuroinflammation of AD have not been well studied. PURPOSE: Neuroinflammation mediated by the NLRP3 inflammasome plays a crucial role in AD. This study was designed to evaluate the effect of SCP-oil on cognitive impairment of AppSwe/PSEN1M146V/MAPTP301L triple transgenic (3 × Tg-AD) mice model and investigate the mechanism underlying its anti-inflammation effects. METHODS: Thirty-two 3 × Tg-AD mice at 12 months and 8 wild-type B6 mice were used for this experiment. The 3 × Tg-AD mice were administered with SCP-oil or donepezil hydrochloride for 8 weeks. Morris water maze test and step-down test were used to evaluate the cognitive ability of mice. The pathological changes, neuroinflammation, and the NLRP3 inflammasome related-protein of AD mice were detected by histomorphological examination, TUNEL staining, immunofluorescence, immunohistochemistry, qRT-PCR, Elisa, and western blot assays. RESULTS: SCP-oil treatment attenuated cognitive dysfunction of 3 × Tg-AD mice. Moreover, SCP-oil also ameliorated characteristics pathological of AD, such as pathological changes damage, deposition of Aß, phosphorylation of Tau, and neuronal loss. Additionally, SCP-oil treatment alleviated the neuroinflammation and inhibited phosphorylation of IKKß, NF-κB, and NLRP3 inflammasome related-protein NLRP3, ASC, Caspase-1, cleaved-Caspase-1, and GSDMD-N in the hippocampus of 3 × Tg-AD mice. CONCLUSION: Overall, SCP-oil contributed to neuroprotection in 3 × Tg-AD mice by reduced activation of NLRP3 inflammasome by inhibiting the NF-κB signaling pathway.

Exploring active ingredients of anti-osteoarthritis in raw and wine-processed Dipsaci Radix based on spectrum-effect relationship combined with chemometrics.

ETHNOPHARMACOLOGICAL RELEVANCE: Dipsaci Radix (DR) is the dry root of the Dipsacus asper Wall. ex DC., which has the function of tonifying the liver and kidney, continuing tendons and bones, and regulating blood vessels. However, there are few reports on the main active ingredients. AIM OF THE STUDY: This study aimed to find the main active components of DR in the treatment of osteoarthritis (OA) by spectrum-effect relationship and compare the differences between RDR and WDR. MATERIALS AND METHODS: Firstly, the high-performance liquid chromatography (HPLC) method was used to establish the fingerprint of DR, and 10 peaks of them were determined by UPLC-Q-TOF/MS. Then, the OA rat model was established by injecting sodium iodoacetate to study the effect of DR on OA. The spectrum-effect relationship was analyzed by grey relational analysis (GRA) and Pearson correlation analysis. RESULTS: According to the pharmacological results, compared with the model group, the cartilage score, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), and Mankin score of rats in low, medium and high dose groups were decreased, and the therapeutic effect of wine-processed DR tended to be better than raw DR at the same dose. Finally, the active components of DR were preliminarily determined as 4 (loganic acid), 6 (chlorogenic acid), 8 (caffeic acid), 14 (dipsanoside B), 16, and 17 (asperosaponin VI) which had a large correlation in GRA and Pearson correlation analysis. CONCLUSION: This study established the spectrum-effect relationship between the raw and wine-processed DR for the first time, which provided a theoretical basis for the study of the pharmacodynamic substance basis of DR before and after processing. This research provided a reference for the subsequent study of DR.

Qingyihuaji Formula promotes apoptosis and autophagy through inhibition of MAPK/ERK and PI3K/Akt/mTOR signaling pathway on pancreatic cancer in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingyihuaji Formula (QYHJ), a widely used traditional Chinese medicine (TCM), has been used to treat patients with cancer in China. However, the effect and mechanism of QYHJ on pancreatic ductal adenocarcinoma (PDAC) remains unclear. AIM OF THE STUDY: This study aimed to explore the roles and evaluate the possible underlying molecular mechanisms of QYHJ and its core component in PDAC using label-free quantitative proteomics in conjunction with network pharmacology-based analysis. MATERIALS AND METHODS: By screening differentially expressed proteins (DEPs) in proteomics and QYHJ-predicted gene sets, we identified QYHJ-related PDAC targets annotated with bioinformatic analysis. A subcutaneous tumor model was established to assess the role of QYHJ in vivo. The effects of quercetin (Que), a core component of QYHJ, on cell proliferation, migration, invasion, apoptosis, and autophagy in SW1990 and PANC-1 cells were investigated in vitro. Immunohistochemistry, western blotting, mRFP-GFP-LC3 adenovirus, and kinase analysis were used to determine the underlying mechanisms. RESULTS: Bioinformatics analysis revealed that 41 QYHJ-related PDAC targets were closely related to the cellular response to nitrogen compounds, positive regulation of cell death, regulation of epithelial cell apoptotic processes, and chemokine signaling pathways. CASP3, SRC, STAT1, PTPN11, PKM, and PAK1 with high expression were identified as hub DEPs in the PPI network, and these DEPs were associated with poor overall survival and STAT 1, MAPK/ERK, and PI3K/Akt/mTOR signaling pathways in PDAC patients. QYHJ significantly promoted tumor death in nude mice. Moreover, quercetin inhibited the proliferation, migration, and invasion of PDAC cells. Additionally, Que induced apoptosis and autophagy in PDAC cells. Mechanistically, QYHJ and Que significantly activated STAT 1 and remarkably inhibited the MAPK/ERK and PI3K/Akt/mTOR signaling pathways in vivo and in vitro, respectively. Importantly, ERK1/2 inactivation contributes to que-induced apoptosis in SW1990 and PANC-1 cells. CONCLUSIONS: These results suggest that QYHJ and Que are promising anti-PDAC avenues that benefit from their multiform mechanisms.

Chemical Composition, Antitumor Properties, and Mechanism of the Essential Oil from Plagiomnium acutum T. Kop.

Plagiomnium acutum T. Kop. (P. acutum) has been used as a traditional Chinese medicine for thousands of years to treat cancer but lacks evidence. The objective of this work was to reveal the chemical composition of P. acutum essential oil (PEO) and explore its potential antitumor activity and molecular mechanism. PEO was prepared by the simultaneous distillation-extraction method and characterized by gas chromatography/mass spectroscopy. CCK8 assay, flow cytometry, western blot, and immunofluorescence techniques were used to analyze the effects and mechanism of PEO against cancer cells. A total of 74 constituents of PEO were identified, with diterpenes (26.5%), sesquiterpenes (23.89%), and alcohols (21.81%) being the major constituents. Two terpenoids, selina-6-en-4-ol and dolabella-3,7-dien-18-ol, were detected in PEO for the first time. PEO showed significant cell growth inhibitory activity on HepG2 and A549 cells by blocking the G1 phase and inducing apoptosis, which may be attributed to its upregulation of p21Cip1 and p27Kip1 proteins and interference with mitochondrial membrane potential effect. Dolabella-3,7-dien-18-ol accounts for 25.5% of PEO and is one of the main active components of PEO, with IC50 values in HepG2 and A549 cells of (25.820 ± 0.216) µg/mL and (23.597 ± 1.207) µg/mL, respectively. These results confirmed the antitumor medicinal value of P. acutum and showed great application potential in the pharmaceutical industry.

Comparative analysis of anti-osteoporosis efficacy in Radix Dipsaci before and after processing with salt based on spectrum-effect relationship.

Radix Dipsaci (RD) is the dry root of the Dipsacus asper Wall. ex DC., which has the effect of strengthening muscles and bones. The purpose of this study was to find the main active ingredients that could improve the anti-osteoporosis efficacy of RD after processing with salt. The fingerprints of raw and salt-processed RD were established by HPLC-DAD to determine the common components. Then, an experimental study on the anti-osteoporosis efficacy was carried out to compared the difference in the efficacy between raw and salt-processed RD. Pharmacological results showed that, compared with the model group, both the raw and salt-processed RD were able to increase the Ca, bone mineral content, bone mineral density, trabeculae bone area and number of trabeculae bone of rats, and reduce the P, alkaline phosphatase, osteocalcin and trabecular bone separation of rats. Under the same dose, the pharmacological effect of salt-processed RD group was better than that of raw RD group. Finally, spectrum-effect relationship between fingerprints and anti-osteoporosis efficacy of RD was assessed by grey relational analysis and entropy method to screening out the ingredients that affect the anti-osteoporosis efficacy in RD after processing with salt. The results showed that the anti-osteoporosis efficacy of salt-processed RD was stronger than that of raw RD, and the pharmacologically active ingredients that improved its anti-osteoporosis efficacy after processing with salt were peak 4, peak 7 (caffeic acid), peak 8 (loganin), peak 12 (isochlorogenic acid C), peak 13 (dipsanoside A) and peak 14. As far as we known, this was the first time to establish the spectrum-effect relationship between RD and anti-osteoporosis efficacy, which laid the foundation for the follow-up research on the pharmacodynamic components and molecular mechanism of RD.

Chang qing formula ameliorates colitis-associated colorectal cancer via suppressing IL-17/NF-κB/STAT3 pathway in mice as revealed by network pharmacology study.

Colitis-associated colorectal cancer (CAC) is a specific type of colorectal cancer (CRC) with high mortality and morbidity, the chronic inflammation in the intestinal mucosal is the characteristic of CAC. Chang Qing formula (CQF) is a Chinese herbal formula used clinically for the treatment of CAC with remarkable clinical efficacy, but its mechanism remains unclear. In the present work, Combined network pharmacology and transcriptomics were used to analyze the potential active ingredients and elucidate molecular mechanism of CQF in treating CAC. Firstly, the constituents migrating to blood of CQF were analyzed and identified by UPLC-Q-TOF-MS/MS, and core genes and pathways were screened by network pharmacology analysis. Encyclopedia of Genes and Genomes (KEGG) analysis showed that the IL-17 signaling pathway involved in CAC may be closely associated with the potential mechanismof action of CQF. Subsequently, the results from animal studies indicated that CQF profoundly reduced tumor numbers and tumor size in AOM/DSS mice. The RNA-seq data was analysed utilizing Ingenuity Pathway Analysis (IPA), and the results supported the idea that CQF exerts a tumour-suppressive effect via the IL-17 signalling pathway. Further studies demonstrated that CQF significantly reduced IL-17A levels, which in turn inhibited NF-κB/IL-6/STAT3 signaling cascade, suppressed MMP9 expression and promoted tumor cell apoptosis. In conclusion, the current study demonstrated that CQF remarkably improved inflammatory tumor microenvironment, and hindered the transformation of inflammation into cancer. These findings may help to design future strategies for the treatment of CAC.

Shen Qi Wan Ameliorates Learning and Memory Impairment Induced by STZ in AD Rats through PI3K/AKT Pathway.

Alzheimer's disease is the most common form of neurodegenerative disease, and increasing evidence shows that insulin signaling has crucial roles in AD initiation and progression. In this study, we explored the effect and underlying mechanism of SQW, a representative formula for tonifying the kidney and promoting yang, on improving the cognitive function in a streptozotocin-induced model of AD rats. We investigated memory impairment in the AD rats by using the Morris water test. HE and Nissl staining were employed to observe the histomorphological changes in the hippocampal. Expression levels of NeuN and proteins related to Tau and apoptosis were measured using immunohistochemistry and Western blotting, respectively. Additionally, we performed RNA sequencing, and the selected hub genes were then validated by qRT-PCR. Furthermore, the protein expression levels of PI3K/AKT pathway-related proteins were detected by Western blot. We found that SQW treatment significantly alleviated learning and memory impairment, pathological damage, and apoptosis in rats, as evidenced by an increased level of NeuN and Bcl-2, and decreased phosphorylation of Tau, Bax, and Caspase-3 protein expression. SQW treatment reversed the expression of insulin resistance-related genes (Nr4a1, Lpar1, Bdnf, Atf2, and Ppp2r2b) and reduced the inhibition of the PI3K/AKT pathway. Our results demonstrate that SQW could contribute to neuroprotection against learning and memory impairment in rats induced by STZ through activation of the PI3K/AKT pathway.

Inoscavin A, a pyrone compound isolated from a Sanghuangporus vaninii extract, inhibits colon cancer cell growth and induces cell apoptosis via the hedgehog signaling pathway.

BACKGROUND: Sanghuangporus vaninii, a large precious medicinal fungus called Sanghuang in China, has significant antitumor activity. We previously reported that a Sanghuangporus vaninii extract could lead to apoptosis in HT-29 cells through the intrinsic apoptotic pathway. We further found that Inoscavin A exhibited anti-colon cancer activity, but its specific mechanisms have not been fully elucidated. METHODS: Inoscavin A was obtained from Sanghuangporus vaninii by the classic phytochemical separation technology. The male BALB/c nude mice were injected with HT-29 colon cancer cells as animal model. In order to observe the pathological changes of tumor section, the hematoxylin-eosin(H&E) staining was applied in the histological analysis. Metabolomics was utilized for the investigation of the overall changes of serum metabolites in animal model, and the potential targets of Inoscavin A were analyzed by Ingenuity Pathway Analysis (IPA). We further employed a molecular docking approach to predict the degree of combination of Inoscavin A and Smo. Then we further performed Western blotting and immunofluorescence analysis to investigate the expression of proteins involved in Hh-related pathways in tumor tissues. In addition, the colony formation assay, scratch-wound assay and transwell migration and invasion assay were conducted to evaluate the anti-colon-cancer activity of Inoscavin A. Concurrently, the mitochondrial membrane potential assay and TUNEL apoptosis assay were detected to demonstrate the effect of Inoscavin A on promoting HT-29 cells apoptosis. Western blot experiments verified the anti-tumor effects of Inoscavin A were modulated the protein expression of Shh, Ptch1, Smo and Gli1 in HT-29 cells. RESULTS: We showed that Inoscavin A, a pyrone compound isolated from the Sanghuangporus vaninii extract, exerted its antitumor activity in an HT-29 colon cancer cell xenograft mouse model. Subsequently, we first time prove that the antitumor effects of Inoscavin A were related to the hedgehog (Hh) signaling pathway. Furthermore, we demonstrated that Smo, the core receptor of the Hh pathway, was critical for the induction of apoptosis of Inoscavin A and that overexpression of this target could significantly rescue cell apoptosis induced by Inoscavin A treatment. CONCLUSION: Thus, our studies first propose that the natural outgrowth Inoscavin A exerted its anti-cancer effects by inhibiting Smo to suppress the activity of the Hh pathway though inhibiting cell proliferation and promoting apoptosis. These findings further indicate that Inoscavin A will be expected to be a prospective remedical compound for the treatment of colon cancer.

Guifu Dihuang Pills Ameliorated Mucus Hypersecretion by Suppressing Muc5ac Expression and Inactivating the ERK-SP1 Pathway in Lipopolysaccharide/Cigarette Smoke-Induced Mice.

Mucus hypersecretion is a hallmark of chronic obstructive pulmonary disease (COPD) and is associated with increasing sputum production and declining pulmonary function. Therefore, reducing mucus secretion can be a new therapeutic opportunity for preventing COPD. The Guifu Dihuang pill (GFDHP) is a classical Chinese medicine and has been used as an immunoregulator for treatment of kidney yang deficiency syndrome, including hypothyroidism, adrenocortical hypofunction, chronic bronchitis, and COPD, for more than 2000 years. However, the protective effects and mechanisms of GFDHP against mucus hypersecretion in COPD remain obscure. The aim of the present study was to explore the inhibitory effects of GFDHP on lipopolysaccharide/cigarette smoke- (LPS/CS-) induced Mucin5ac (Muc5ac) overproduction and airway goblet cell hyperplasia in mice. The mice were randomly assigned into 6 groups: control, model, GFDHP-L, GFDHP-M, GFDHP-H, and dexamethasone. The mice were given LPS twice through intranasal inhalation and then exposed to CS daily for 6 weeks. Three doses of GFDHP were orally administered daily during the last 3 weeks of the experiment. Pulmonary function was examined with an EMKA pulmonary system, and pulmonary hyperpermeability and lung damage were evaluated with an in vivo imaging system. Inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were detected with a cell count analyzer and though ELISA analysis, respectively. Lung pathological changes and airway goblet cell hyperplasia were analyzed with hematoxylin and eosin and Alcian blue periodic acid Schiff staining. The protein expression levels of Muc5ac and extracellular signal-regulated kinase (ERK)-specificity protein1 (SP1) signaling pathway were measured with Western blot and immunohistochemistry. The results demonstrated that GFDHP improved pulmonary function and suppressed mouse pulmonary hyperpermeability and edema. GFDHP suppressed inflammatory cell infiltration and cytokine release in BALF, thereby elevating pulmonary function. It ameliorated lung pathological changes and airway goblet cell hyperplasia, and suppressed expression levels of Muc5ac mRNA and protein and phospho-ERK and SP1 levels in the lung tissues of the COPD mice. In conclusion, GFDHP inhibited mucus hypersecretion induced by LPS/CS by suppressing the activation of the ERK-SP1 pathway.

Rapid Quality Identification of Decoction Pieces of Crude and Processed Corydalis Rhizoma by Near-Infrared Spectroscopy Coupled with Chemometrics.

In order to identify the quality of crude and processed Corydalis Rhizoma decoction pieces, the research established a simple, fast, reliable, and validated near-infrared qualitative and quantitative model combined with chemometrics. 51 batches of crude and 40 batches of processed Corydalis Rhizoma from the Zhejiang and Jiangsu provinces of China were collected and analyzed. Crude and processed Corydalis Rhizoma samples were crushed to obtain NIR spectra. The content of seven alkaloids in crude and processed Corydalis Rhizoma was determined by high-performance liquid chromatography (HPLC). Pretreatment methods were screened such as normalization methods, offset filtering methods, and smoothing. Combined with partial least squares-discriminant analysis (PLS-DA) and partial least squares (PLS), the qualitative and quantitative models of crude and processed Corydalis Rhizoma were established, and the correlation coefficient (R 2), root mean square error of calibration (RMSEC), and root mean square error of prediction (RMSEP) were used as evaluation indexes. Tetrahydropalmatine was used as an example for screening pretreatment methods; the results showed that MSC combined with the second derivative and no smoothing and the model with the wavelength range of 10000-5000 cm-1 had the best predictive ability and applied to all seven alkaloid components. Among them, the correlation coefficients were all higher than 0.99, and RMSEC and RMSEP were all less than 1%. The qualitative and quantitative model of the seven alkaloids in Corydalis Rhizoma can effectively identify the crude and processed Corydalis Rhizoma and determine the content of the seven alkaloids. By studying the NIR qualitative and quantitative models of crude and processed Corydalis Rhizoma, we can achieve rapid discrimination and quantitative prediction of crude and processed Corydalis Rhizoma. These methods can greatly improve the efficiency of traditional Chinese medicine analysis and provide a strong scientific basis for the quality identification and control of traditional Chinese medicine.

Organic matter affects phosphorus recovery during vivianite crystallization.

Vivianite crystallization is a promising route for phosphorus (P) recovery from P-rich wastewater. However, organic matter (OM) in wastewater may influence vivianite formation. In this study, the effects of four representative OMs, glucose, bovine serum albumin (BSA), humic acid (HA) and sodium alginate (SA), on P recovery by vivianite were investigated. The results showed that P recovery efficiency was inhibited by HA and SA, declining by 3.7% and 12.1% under HA (100 mg/L) and SA (800 mg/L), respectively. BSA, HA and SA affected the aggregated form of vivianite crystals. Vivianite particle size decreased in the presence of HA and SA. Subsequent mechanistic exploration indicated that the complexation between the OM and Fe2+ was the main cause of P recovery efficiency reduction. The coprecipitation of HA and SA with vivianite could reduce the zeta potential on the crystal surface, resulting in a smaller particle size. The nucleation sites provided by BSA and SA could transfer vivianite from single plate-like agglomerate to multilayer plate-like agglomerate. This study provided a better understanding of P recovery by vivianite from OM-rich wastewater.

Potential of using basa catfish oil as a promising alternative deep-frying medium: A thermo-oxidative stability study.

Basa catfish is a good source for fish oil extraction, which was believed to have good thermo-oxidative stability because of its similar fatty acid composition to that of palm olein (PO). The thermo-oxidative stability of PO, basa catfish oil (FO), and palm olein-basa fish oil blend (PO-FO; ratio 1:1) was evaluated after 75 frying cycles. No significant difference was observed in p-anisidine value, TOTOX value, conjugated trienes, monomeric oxidized triacylglycerols, and free fatty acids concentration after frying. Moreover, compared to PO, FO exhibited lighter color, lower acid value, conjugated dienes, polymerized triacylglycerol, and total polar content. The PO-FO blend also demonstrated a more favorable frying stability compared to the other two frying systems. These findings indicated that FO could be proposed as a promising alternative to common PO, and its blending with other vegetable oils at an appropriate ratio might improve the overall oil frying quality for future industrial applications.

The Protective Effect of Shen Qi Wan on Adenine-Induced Podocyte Injury.

Podocytes are a special type of differentiated epithelial cells that maintain the glomerular filtration barrier in the kidney. Injury or damages in podocytes can cause kidney-related disorders, like CKD. The injury or dysfunction of podocytes can occur by different metabolic disorders. Due to the severity and complexity of podocyte injuries, this state is considered as a serious health issue worldwide. Here, we examined and addressed the efficacy of an alternative Chinese medicine, Shen Qi Wan (SQW), on podocyte-related kidney injury. We evaluated the role and mechanism of action of SQW in podocyte injury. We observed that SQW significantly reduced 24-hour urinary protein and blood urea nitrogen levels and alleviated the pathological damage caused by adenine. Moreover, SQW significantly decreased the expression of nephrin and increased the expression of WT1 and AQP1 in the kidney of mice treated with adenine. We observed that SQW did not effectively reduce the high level of proteinuria in AQP1-/- mice indicating the prominent role of AQP1 in the SQW-ameliorating pathway. Transmission electron microscopy (TEM) images indicated the food processes effacement in AQP1-/- mice were not lessened by SQW. In conclusion, podocyte injury could alter the pathological nature of the kidney, and SQW administration relieves the nature of pathogenesis by activating AQP1.

Simultaneous removal of nitrate and sulfate using an up-flow three-dimensional biofilm electrode reactor: Performance and microbial response.

Nitrate removal from low carbon water is a problem in the water treatment, especially in the presence of high sulfate. In this work, an up-flow three-dimensional biofilm electrode reactor (3D-BER) was established to remove nitrate and sulfate from low organic carbon water. Results indicated that sulfate negatively affected nitrate removal. Moreover, high electric current and short hydraulic retention time deteriorated the performance of nitrate and sulfate removal. When the influent of SO42- was 150 mg/L, the removal efficiency of NO3--N and SO42- was 88.49 ± 4.5% and 29.35 ± 5.5%, respectively. The high-throughput sequencing revealed that denitrifying bacteria dominated in the lower part of the reactor while sulfate reducing bacteria dominated in the upper part of the reactor. It was speculated that oxidation products of sulfide could serve as supplementary electron donors to enhance nitrate removal in the 3D-BER.