Therapeutic potential of curcumin on the cognitive decline in animal models of Alzheimer's disease: a systematic review and meta-analysis.

Curcumin, a polyphenol derived from the herb turmeric, has emerged as a prospective potential therapy in the treatment of Alzheimer's disease (AD). However, the efficacy of curcumin treatment in improving cognitive decline caused controversy recently. We aimed to systematically review the effect of curcumin on cognitive impairment in an animal model of AD. We conducted an exhaustive database search of related studies. Two investigators identified studies and independently extracted data. Stratified meta-analyses and meta-regression analyses were carried out to explore the sources of heterogeneity. Publication bias was assessed using funnel plots and Egger's test. Our systematic review included 33 articles. A meta-analysis of 29 publications showed that curcumin exerts significant positive effects on cognitive performance. For acquisition, the global estimated effect of curcumin was - 2.027 (95% CI - 2.435 to - 1.619, p < 0.001); for retention, the global estimated effect of curcumin was 1.606 (95% CI 1.101 to 2.111, p < 0.001). The stratified meta-analysis demonstrated that an increased effect size depended on diverse study characteristics. Additionally, publication bias was detected. We conclude that curcumin may reduce cognitive deficits in experimental AD. Furthermore, we emphasize that additional well-designed and well-reported animal studies are needed to inform further clinical studies.

Arts therapies for mental disorders in COVID-19 patients: a comprehensive review.

Background and objective: The COVID-19 global pandemic has necessitated the urgency for innovative mental health interventions. We performed a comprehensive review of the available literature on the utility and efficacy of arts therapies in treating mental health problems, with special emphasis on their deployment during the COVID-19 pandemic, aiming to provide some evidence for the application of this therapy. Methods: The potential studies were systematically sourced from five authoritative databases: PubMed, Embase, the Cochrane Library, Web of Science, and the CNKI database. The evaluation of these studies was conducted based on stringent criteria, including validity, suitability, therapeutic potential, and consistency. Each piece of included literature was meticulously scored in accordance with these criteria, thus ensuring the inclusion of only the most robust studies in this review. The data from these Randomized Controlled Trials (RCTs) were carefully extracted using the PICO(S) framework, ensuring a comprehensive and systemic approach to data collection. In order to emphasize the variability in the effects of differing arts therapies on COVID-19-induced psychiatric disturbances, the sourced literature was systematically categorized and scrutinized based on distinct modalities. Results: Out of the 7,250 sourced articles, 16 satisfied the inclusion conditions. The therapies were predominantly meditation (n = 7), supplemented by individual studies on color therapy (n = 3), music therapy (n = 2), and single studies on horticultural therapy, dance therapy, mindfulness and music therapy, and yoga and music therapy (n = 4 collectively). These various forms of arts therapies had a positive short to medium-term impact on the mental health of COVID-19 patients. Besides improving patients' physical and mental health, these therapies can also be employed to mitigate mental health issues among healthcare professionals. Conclusion: The COVID-19 pandemic has profound and long-lasting implications for public mental health. Diverse forms of arts therapies are potentially effective in addressing related psychiatric symptoms. The integration of artificial intelligence might further enhance the efficacy and scalability of arts therapies in future implementations.

Baicalin Reduces Immune Cell Infiltration by Inhibiting Inflammation and Protecting Tight Junctions in Ischemic Stroke Injury.

Ischemic stroke is a serious health hazard that lacks effective treatment strategies. This study aims to investigate baicalin's effect on tight junctions and immune cell infiltration after ischemic stroke injury. Rat brain microvascular endothelial cells (BMECs) were treated with OGD/R to establish an in vitro model. Caspase-3, Bax, Bcl-2, zonula occludens-1 (ZO-1), occludin, claudin-5, tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-6, inducible nitric oxide synthase (iNOS), Toll-like receptor (TLR) 2, TLR4, and nuclear factor-kappa B (NF-[Formula: see text]B) expressions were detected using qRT-PCR and western blotting. ZO-1, TNF-[Formula: see text], iNOS, IL6, CD31, and ZO-1 expressions were examined using immunofluorescence. A tube formation assay was performed to measure angiogenesis. An ischemia-reperfusion model in rats was established by middle cerebral artery occlusion. The infarct volume was observed using 2,3,5-triphenyltetrazolium chloride staining. TNF-[Formula: see text], iNOS, and IL6 levels in the serum were tested using ELISA. Flow cytometry was performed to examine immune cell inflammatory infiltration. Baicalin had no significant effect on the proliferation of normal BMECs. Baicalin inhibited apoptosis, protected against tight junction injury, and alleviated the inflammatory response in OGD/R-induced BMECs and IR rats, with the highest dose (25[Formula: see text][Formula: see text]g/mL) exerting a superior effect. Baicalin decreased the neurological function score, infarct volume, and brain water content, relieved brain morphological changes, and inhibited immune cell infiltration in vivo. In conclusion, baicalin could reduce BMECs apoptosis, protect tight junctions, and resist immune cell infiltration, thereby alleviating ischemic stroke. Our findings potentially provide a novel treatment strategy for ischemic stroke.

Art therapy as an adjuvant treatment for schizophrenia: A protocol for an updated systematic review and subgroup meta-analysis of randomized clinical trials following the PRISMA guidelines.

BACKGROUND: The efficacy of art therapy as an adjuvant treatment for schizophrenia remains inconclusive, and variation in the effects of art therapy on schizophrenia by the type of schizophrenia, severity of schizophrenia, type of art therapy, follow-up duration, or different populations has never been systematically assessed. The objective of this study is to systematically evaluate the effects of art therapy on schizophrenia and to determine whether there are some potential influencing factors affecting the effects of art therapy. METHODS: Seven online databases will be searched from their inception until June 30, 2022. All the relevant randomized clinical trials (RCTs) comparing art therapy plus standardized treatment versus standardized treatment alone for schizophrenia will be selected and assessed for inclusion. The Cochrane risk-of-bias tool will be used to evaluate the methodological quality of the included RCTs. Review Manager 5.4 will be used to analyze all the data obtained. Mental health symptoms are defined as the primary outcome, and the secondary outcomes include the Global Assessment of Functioning score, quality of life, functional remission, and the level of self-esteem. Subgroup analyses will be performed based on the type of schizophrenia, severity of schizophrenia, type of art therapy, follow-up duration, or different populations. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSIONS: This updated systematic review and subgroup meta-analysis will evaluate the effects of art therapy as adjunctive treatment to standardized treatment in patients with schizophrenia and determine whether there are some potential confounding variables affecting the effects of art therapy on the outcomes of schizophrenia patients, thus strengthening the evidence base for the clinical application of this combination therapy for schizophrenia.

The potential mechanism of Longsheyangquan Decoction on the treatment of bladder cancer: Systemic network pharmacology and molecular docking.

Our goal was to explore the bioactive constituents of Longsheyangquan (LSYQ) Decoction and elucidate its mechanisms on the treatment of bladder cancer (BCa). A total of 38 compounds were selected based on their pharmacokinetic properties in three large traditional Chinese medicine (TCM) databases. 654 putative targets of LSYQ Decoction were predicted using a structure-based, reverse-docking algorithm online, of which 343 overlapped with BCa-related protein-coding genes. The protein-protein interaction (PPI) network was constructed to perform module analysis for further Gene Ontology (GO) annotations and Kyoto Encyclopedia Genes and Genomes (KEGG) pathway enrichment analysis, which identified CDK2, EGFR, MMP9 and PTGS2 as hub targets. The TCM-compound-target network and compound-target-pathway network together revealed that quercetin, diosmetin, enhydrin and luteolin were the main components of LSYQ Decoction. Finally, molecular docking showed the affinity between the key compounds and the hub target proteins to verify the accuracy of drug target prediction in the first place. The present study deciphered the core components and targets of LSYQ Decoction on the treatment of BCa in a comprehensive systemic pharmacological manner.

Genome-wide analysis of hippocampal transfer RNA-derived small RNAs identifies new potential therapeutic targets of Bushen Tiansui formula against Alzheimer's disease.

OBJECTIVE: Bushen Tiansui formula (BSTSF), a traditional Chinese medicine prescription, has been widely used to treat Alzheimer's disease (AD). However, the mechanisms underlying its effects remain largely unknown. In this study, a rat AD model was used to study the effects of BSTSF on cognitive performance and expression of transfer RNA-derived small RNAs (tsRNAs) in the hippocampus, to determine whether treatment of AD with BSTSF could regulate the expression of tsRNAs, a novel small non-coding RNA. METHODS: To generate a validated AD model, oligomeric amyloid-ß1-42 (Aß1-42) was injected intracerebroventricularly into rats. The Morris water maze (MWM) test was used to evaluate rat cognitive performance, and tsRNA-sequencing was conducted to examine tsRNA expression in the rat hippocampus. Potential targets were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatic analyses were conducted to investigate the biological function of candidate tsRNAs. RESULTS: The learning and memory deficits of Aß1-42-induced AD rats, assessed by MWM tests, were clearly ameliorated by BSTSF treatment. A total of 387 tsRNAs were detected in the rat hippocampus. Among them, 13 were significantly dysregulated in AD rats compared with sham control rats, while 57 were markedly altered by BSTSF treatment, relative to untreated AD rats (fold change ≥ 2 and P < 0.05). Moreover, six BSTSF treatment-related tsRNAs were identified and validated by qRT-PCR. Bioinformatic analyses indicated that the six treatment-related tsRNAs had potential therapeutic roles, via multiple signaling pathways and Gene Ontology biological functions, including cyclic adenosine monophosphate and retrograde endocannabinoid signaling. CONCLUSION: This study identified a previously uncharacterized mechanism underlying the effects of BSTSF in alleviating the learning and memory deficits in Aß1-42-induced AD rats, demonstrating that tsRNAs are potential therapeutic targets of BSTSF in the treatment of AD.

Integrated meta-analysis, network pharmacology, and molecular docking to investigate the efficacy and potential pharmacological mechanism of Kai-Xin-San on Alzheimer's disease.

CONTEXT: Kai-Xin-San (KXS) has been used to treat Alzheimer's disease (AD) for thousands of years. However, no quantitative data regarding AD treatment using KXS are available. Moreover, its active compounds and mechanism of action for the treatment of AD remain largely unclear. OBJECTIVES: To evaluate the efficacy and the potential pharmacological mechanisms of KXS in AD treatment. MATERIALS AND METHODS: A systematic collection of KXS experiments was conducted from PubMed, Web of Science, Embase, CNKI, VIP, and Wanfang Data up to February, 2020. Review Manager 5 software was used for meta-analysis. In network pharmacology, components of KXS were screened, AD-related genes were then identified and the 'component-target-pathway' network constructed. Molecular docking was finally employed for in silico simulation matching between representative KXS compounds and their target genes. RESULTS: Meta-analysis revealed that KXS improves the cognitive benefits in AD models by reducing the time of escape latency (SMD = -16.84) as well as increasing the number of cross-platform (SMD = 2.56) and proportion of time in the target quadrant (SMD = 7.52). Network pharmacology identified 25 KXS active compounds and 44 genes targets. DRD2, MAOA, ACHE, ADRA2A and CHRM2 were core target proteins. Besides, 22 potential pathways of KXS were identified, like cholinergic synapses, the cGMP/PKG pathway and calcium signalling. Molecular docking showed that stigmasterol, aposcopolamine and inermin can closely bind three targets (ACHE, ADRA2A and CHRM2). DISCUSSION AND CONCLUSION: These findings suggest that KXS exerts effect on AD through multi-target, multi-component and multi-pathway mechanism. Future studies may explore the active components of KXS.

A Network Pharmacology Analysis of the Active Components of the Traditional Chinese Medicine Zuojinwan in Patients with Gastric Cancer.

BACKGROUND Zuojinwan (ZJW) is a traditional Chinese prescription normally used for gastritis. Several studies indicated that it could fight against gastric cancer. This study was designed to determine the potential pharmacological mechanism of ZJW in the treatment of gastric cancer. MATERIAL AND METHODS Bioactive compounds and potential targets of ZJW and related genes of gastric cancer were retrieved from public databases. Pharmacological mechanisms including crucial ingredients, potential targets, and signaling pathways were determined using protein-protein interaction (PPI) and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Virtual docking was performed to validate the findings. RESULTS Network analysis identified 47 active ZJW compounds, and 48 potential ZJW target genes linked to gastric cancer. Quercetin, beta-sitosterol, isorhamnetin, wogonin, and baicalein were identified as potential candidate agents. Our PPI analysis results combined with previously published results indicated that matrix metalloproteinases family members MMP9, MMP1, and MMP3 may play key roles in the anti-gastric cancer effect of ZJW. Molecular docking analysis showed that these crucial targets had good affinity for the representative components in ZJW. GO and KEGG enrichment analysis showed that ZJW target genes functioned in multiple pathways for treating gastric cancer, including interleukin-17 signaling and platinum drug resistance. CONCLUSIONS Our results illuminate the active ingredients, associated targets, biological processes, and signaling pathways of ZJW in the treatment of gastric cancer. This study enhances our understanding of the potential effects of ZJW in gastric cancer and demonstrates a feasible method for discovering potential drugs from Chinese medicinal formulas.

Network Pharmacology-Based Prediction and Verification of the Active Ingredients and Potential Targets of Zuojinwan for Treating Colorectal Cancer.

BACKGROUND: Zuojinwan (ZJW), a famous Chinese medicine formula, has been widely used to treat colorectal cancer (CRC). However, its bioactive compounds, potential targets, and molecular mechanism remain largely elusive. AIM: A network pharmacology-based strategy combined with molecular docking studies and in vitro validation were employed to investigate bioactive compounds, potential targets, and molecular mechanism of ZJW against CRC. MATERIALS AND METHODS: Bioactive compounds and potential targets of ZJW, as well as related genes of CRC, were acquired from public databases. Important ingredients, potential targets, and signaling pathways were determined through bioinformatics analysis, including protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking and cell experiments were performed to further verify the findings. RESULTS: A total of 36 bioactive ingredients of ZJW and 163 gene targets of ZJW were identified. The network analysis revealed that quercetin, baicalein, wogonin, beta-sitosterol, and isorhamnetin may be candidate agents. The AKT1, JUN, CDKN1A, BCL2L1, and NCOA1 could become potential drug targets. The KEGG indicated that PI3K-AKT signaling pathway may play an important role in the effect of ZJW against CRC. Molecular docking suggested that quercetin, baicalein, and wogonin combined well with AKT1 and JUN. The in vitro experiment showed that quercetin, the most important ingredient of ZJW, could induce apoptosis of HCT116 cells through PI3K-Akt signaling pathway. This finding was congruent with the prediction obtained through the network pharmacology approach. CONCLUSION: This study comprehensively illuminated the active ingredients, potential targets, and molecular mechanism of ZJW against CRC. It also provided a promising approach to uncover the scientific basis and therapeutic mechanism of traditional Chinese medicine (TCM) formula treating for disease.

Integrated Metabolomic and Lipidomic Analysis Reveals the Neuroprotective Mechanisms of Bushen Tiansui Formula in an Aß1-42-Induced Rat Model of Alzheimer's Disease.

Bushen Tiansui Formula (BSTSF) is a traditional Chinese medicine prescription. It has been widely applied to treat Alzheimer's disease (AD) in the clinic; however, the mechanisms underlying its effects remain largely unknown. In this study, we used a rat AD model to study the effects of BSTSF on cognitive performance, and UPLC-MS/MS-based metabolomic and lipidomic analysis was further performed to identify significantly altered metabolites in the cerebral cortices of AD rats and determine the effects of BSTSF on the metabolomic and lipidomic profiles in the cerebral cortices of these animals. The results revealed that the levels of 47 metabolites and 30 lipids primarily associated with sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism were significantly changed in the cerebral cortices of AD rats. Among the altered lipids, ceramides, phosphatidylethanolamines, lysophosphatidylethanolamines, phosphatidylcholines, lysophosphatidylcholines, phosphatidylserines, sphingomyelins, and phosphatidylglycerols showed robust changes. Moreover, 34 differential endogenous metabolites and 21 lipids, of which the levels were mostly improved in the BSTSF treatment group, were identified as potential therapeutic targets of BSTSF against AD. Our results suggest that lipid metabolism is highly dysregulated in the cerebral cortices of AD rats, and BSTSF may exert its neuroprotective mechanisms by restoring metabolic balance, including that of sphingolipid metabolism, glycerophospholipid metabolism, alanine, aspartate, and glutamate metabolism, and D-glutamine and D-glutamate metabolism. Our data may lead to a deeper understanding of the AD-associated metabolic profile and shed new light on the mechanism underlying the therapeutic effects of BSTSF.

Integrated network pharmacology analysis and serum metabolomics to reveal the cognitive improvement effect of Bushen Tiansui formula on Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Tiansui Formula (BSTSF) is a traditional Chinese medicine formula used clinically to treat Alzheimer's disease (AD) for many years. Previously, we have partially elucidated the mechanisms involved in the therapeutic effects of BSTSF on AD. However, the underlying mechanisms remain largely unclear. AIM OF THE STUDY: The aim of this study was to further investigate the therapeutic effects of BSTSF on AD using an integrated strategy of network pharmacology and serum metabolomics. MATERIALS AND METHODS: The rat models of AD were established using Aß 1-42 injection, and morris water maze test was used to evaluate the efficacy of BSTSF on AD. Next, network pharmacology analysis was applied to identify the active compounds and target genes, which might be responsible for the effect of BSTSF. Then, a metabolomics strategy has been developed to find the possible significant serum metabolites and metabolic pathway induced by BSTSF. Additionally, two parts of the results were integrated to confirm each other. RESULTS: The results of the network pharmacology analysis showed 37 compounds and 64 potential target genes related to the treatment of AD with BSTSF. The functional enrichment analysis indicated that the potential mechanism was mainly associated with the tumor necrosis factor signaling pathway and phosphatidylinositol 3 kinase/protein kinase B signaling pathway. Based on metabolomics, 78 differential endogenous metabolites were identified as potential biomarkers related to the BSTSF for treating AD. These metabolites were mainly involved in the relevant pathways of linoleic acid metabolism, α-linolenic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and arginine and proline metabolism. These findings were partly consistent with the findings of the network pharmacology analysis. CONCLUSIONS: In conclusion, our results solidly supported and enhanced out current understanding of the therapeutic effects of BSTSF on AD. Meanwhile, our work revealed that the proposed network pharmacology-integrated metabolomics strategy was a powerful means for identifying active components and mechanisms contributing to the pharmacological effects of traditional Chinese medicine.

A Network Pharmacology-Based Strategy For Predicting Active Ingredients And Potential Targets Of LiuWei DiHuang Pill In Treating Type 2 Diabetes Mellitus.

BACKGROUND: Traditional Chinese medicine (TCM) formulations have proven to be advantageous in clinical treatment and prevention of disease. LiuWei DiHuang Pill (LWDH Pill) is a TCM that was employed to treat type 2 diabetes mellitus (T2DM). However, a holistic network pharmacology approach to understanding the active ingredients and the therapeutic mechanisms underlying T2DM has not been pursued. METHODS: A network pharmacology approach including drug-likeness evaluation, oral bioavailability prediction, virtual docking, and network analysis has been used to predict the active ingredients and potential targets of LWDH Pill in the treatment of type 2 diabetes. RESULTS: The comprehensive network pharmacology approach was successfully to identify 45 active ingredients in LWDH Pill. 45 active ingredients hit by 163 potential targets related to T2DM. Ten of the more highly predictive components (such as :quercetin, Kaempferol, Stigmasterol, beta-sitosterol, Kadsurenone, Diosgenin, hancinone C, Hederagenin, Garcinone B, Isofucosterol) are involved in anti-inflammatory, anti-oxidative stress, and the reduction of beta cell damage. LWDH Pill may play a role in the treatment of T2DM and its complications (atherosclerosis and nephropathy) through the AGE-RAGE signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. CONCLUSION: Based on a systematic network pharmacology approach, our works successfully predict the active ingredients and potential targets of LWDH Pill for application to T2DM and helps to illustrate mechanism of action on a comprehensive level. This study provides identify key genes and pathway associated with the prognosis and pathogenesis of T2DM from new insights, which also demonstrates a feasible method for the research of chemical basis and pharmacology in LWDH Pill.

UPLC-QTOF/MS-based metabolomics analysis of plasma reveals an effect of Xue-Fu-Zhu-Yu capsules on blood-stasis syndrome in CHD rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Blood-stasis syndrome (BSS) is a specific ZHENG type of coronary heart disease (CHD) in traditional Chinese medicine (TCM). The Xue-Fu-Zhu-Yu (XFZY) decoction is a common herbal formula that has been used for several centuries to treat BSS, but its mechanism has not been thoroughly elucidated to date. AIM OF THE STUDY: In this study, serum lipid, blood haemorheology and metabolomics analyses were performed to depict a complete profile of XFZY capsules for the treatment of CHD with BSS and to reveal the potential mechanism of the XFZY capsules. MATERIALS AND METHODS: A rat model of CHD with BSS was generated by combining a high-fat diet (HFD) with a left anterior descending coronary artery (LAD) ligation. After four weeks of treatment with XFZY capsules or simvastatin pills, an echocardiography was performed for a therapeutic evaluation. Blood samples and heart tissues were then collected for further analyses. A UPLC-QTOF/MS-based metabolomics analysis of the plasma was performed, and all metabolic features were fit by PCA and OPLS-DA pattern for the biomarker screen. The identified biomarkers were later implemented into a metabolic pathway analysis. Furthermore, we used qRT-PCR and Western blot analyses to verify the treatment effects of the XFZY capsules. RESULTS: A total of 49 metabolites (VIP>1.0, p < 0.05, RSD%<20%) were identified in the Model rats, and 27 metabolites (VIP>1.0, p < 0.05, RSD%<20%) were identified in the XFZY-H rats. The results of the pathway analysis indicated that the XFZY capsules treated CHD primarily by regulating cardiac energy, phospholipid, polyunsaturated fatty acid (PUFA) and amino acid metabolism. In addition, blood viscosity and serum lipid assays suggested that XFZY capsules could decrease serum triglycerides, total cholesterol, low-density lipoprotein cholesterol and whole blood viscosity at a low shear rate. CONCLUSION: This study demonstrated that the XFZY capsule effectively decreases serum lipids and whole blood viscosity in CHD with BSS. The underlying metabolic mechanism mainly included improving cardiac energy supply, reducing phospholipid peroxide, maintaining the PUFA metabolic balance and regulating amino acid metabolism.

Jianpi Jiedu decoction, a traditional Chinese medicine formula, inhibits tumorigenesis, metastasis, and angiogenesis through the mTOR/HIF-1α/VEGF pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine has been utilized for the treatment of cancer. Jianpi Jiedu decoction (JPJD), a traditional Chinese medicine formula, has been used for the treatment of colorectal cancer for decades. However, the underlying molecular mechanistic basis for the effect of JPJD on colorectal cancer is poorly understood. AIM OF THE STUDY: The aim of this study was to identify the effects of JPJD on human colon cancer cells in vitro as well as in vivo and to investigate the mechanistic basis for the anticancer effect of JPJD. MATERIALS AND METHODS: The in vitro antitumor activity of JPJD was assessed by MTT assay, flow cytometric analysis, wound-healing assay, transwell assays, and tube formation assays in order to assess cell activity, apoptosis, migration, invasion, and angiogenesis, respectively. The anticancer properties of JPJD in vivo were assessed by immunohistochemistry in a nude mouse xenograft model of HCT116 cells. In addition, the level of mTOR/HIF-1α/VEGF signaling pathway proteins in HCT116 cells and tumor tissue was evaluated by immunoblotting. RESULTS: In vitro, JPJD significantly inhibited colorectal cancer cell lines viability and proliferation. Flow cytometry analysis demonstrated JPJD to induce HCT116 cell apoptosis. Additionally, JPJD effectively suppressed tumor cell migration, invasion, and angiogenesis by inhibiting the mTOR/HIF-1α/VEGF signaling pathway. In vivo, JPJD significantly inhibited HCT116 tumor growth in athymic nude mice, decreased the levels of CD34 as well as VEGF, and downregulated the mTOR/HIF-1α/VEGF pathway. CONCLUSIONS: JPJD treatment produced anti-colorectal tumor effects by inhibiting tumorigenesis, metastasis, as well as angiogenesis through the mTOR/HIF-1α/VEGF pathway. Thus, these results provide a strong rationale for the therapeutic use of JPJD in cancer treatment. Further studies are required to investigate the mechanisms underlying anti-CRC effect of JPJD.

iTRAQ-Based Quantitative Proteomics Analysis of the Protective Effect of Yinchenwuling Powder on Hyperlipidemic Rats.

Yinchenwuling powder (YCL) is an effective traditional Chinese medicine formula to modulate lipid levels. In this study, we established hyperlipidemic rat models and treated them with YCL. The serum concentrations of lipid, malondialdehyde (MDA), endothelin-1 (ET-1), and calcitonin gene-related peptide (CGRP) were measured. Adventitia-free vascular proteins between hyperlipidemic rats and YCL-treated rats were identified using iTRAQ-based quantitative proteomics research approach. Proteins with 1.3-fold difference were analyzed through bioinformatics, and proteomic results were verified by Western blot. The results showed that the serum levels of TC, TG, LDL-C, ET-1, and MDA were significantly decreased, whereas the HDL-C and CGRP levels were significantly increased in the YCL-treated group. Proteomics technology identified 4,382 proteins, and 15 proteins were selected on the basis of their expression levels and bioinformatics. Of these proteins, 2 (Adipoq and Gsta1) were upregulated and 13 (C3, C4, C6, Cfh, Cfp, C8g, C8b, Lgals1, Fndc1, Fgb, Fgg, Kng1, and ApoH) were downregulated in the YCL-treated rats. Their functions were related to immunity, inflammation, coagulation and hemostasis, oxidation and antioxidation, and lipid metabolism and transport. The validated results of ApoH were consistent with the proteomics results. This study enhanced our understanding on the therapeutic effects and mechanism of YCL on hyperlipidemia.

Melanin nanoparticles derived from a homology of medicine and food for sentinel lymph node mapping and photothermal in vivo cancer therapy.

The use of non-toxic or low toxicity materials exhibiting dual functionality for use in sentinel lymph node (SLN) mapping and cancer therapy has attracted considerable attention during the past two decades. Herein, we report that the natural black sesame melanin (BSM) extracted from black sesame seeds (Sesamum indicum L.) shows exciting potential for SLN mapping and cancer photothermal therapy. Aqueous solutions of BSM under neutral and alkaline conditions can assemble into sheet-like nanoparticles ranging from 20 to 200 nm in size. The BSM nanoparticles were encapsulated by liposomes to improve their water solubility and the encapsulated and bare BSM nanoparticles were both non-toxic to cells. Furthermore, the liposome-encapsulated BSM nanoparticles (liposome-BSM) did not exhibit any long-term toxicity in mice. The liposome-BSM nanoparticles were subsequently used to passively target healthy and tumor-bearing mice SLNs, which were identified by the black color of the nanoparticles. BSM also strongly absorbed light in the near-infrared (NIR) range, which was rapidly converted to heat energy. Human esophagus carcinoma cells (Eca-109) were killed efficiently by liposome-BSM nanocomposites upon NIR laser irradiation. Furthermore, mouse tumor tissues grown from Eca-109 cells were seriously damaged by the photothermal effects of the liposome-BSM nanocomposites, with significant tumor growth suppression compared with controls. Given that BSM is a safe and nutritious biomaterial that can be easily obtained from black sesame seed, the results presented herein represent an important development in the use of natural biomaterials for clinical SLN mapping and cancer therapy.

A Multimodal System with Synergistic Effects of Magneto-Mechanical, Photothermal, Photodynamic and Chemo Therapies of Cancer in Graphene-Quantum Dot-Coated Hollow Magnetic Nanospheres.

In this study, a multimodal therapeutic system was shown to be much more lethal in cancer cell killing compared to a single means of nano therapy, be it photothermal or photodynamic. Hollow magnetic nanospheres (HMNSs) were designed and synthesized for the synergistic effects of both magneto-mechanical and photothermal cancer therapy. By these combined stimuli, the cancer cells were structurally and physically destroyed with the morphological characteristics distinctively different from those by other therapeutics. HMNSs were also coated with the silica shells and conjugated with carboxylated graphene quantum dots (GQDs) as a core-shell composite: HMNS/SiO2/GQDs. The composite was further loaded with an anticancer drug doxorubicin (DOX) and stabilized with liposomes. The multimodal system was able to kill cancer cells with four different therapeutic mechanisms in a synergetic and multilateral fashion, namely, the magnetic field-mediated mechanical stimulation, photothermal damage, photodynamic toxicity, and chemotherapy. The unique nanocomposites with combined mechanical, chemo, and physical effects will provide an alternative strategy for highly improved cancer therapy efficiency.