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Xihuang pill has been utilized to treat cancer for more than three hundred years in China. The molecular mechanisms of Xihuang pill in treating glioblastoma remains unclear. This study aimed to explore the core molecular mechanisms of Xihuang pill in treating glioblastoma by an integrative pharmacology-based investigation. The main active compounds of Xihuang pill were identified from TCMSP, BATMAN-TCM, TCMID and CNKI. Glioblastoma-related therapeutic targets were retrieved from GeneCards and UniProt. Subsequently, a protein-protein interaction (PPI) network analysis was constructed using STRING. GO and KEGG enrichment were performed to analyze the intersection targets between the active compounds of Xihuang pill and glioblastoma. Based on the above analysis, we built a CTP network. The in vitro and in vivo experiments were further performed to validate the crucial molecular targets of Xihuang pill for the treatment of glioblastoma. A total of sixty active compounds of Xihuang pill and ten potential targets related to glioblastoma were found. Based on topological analysis, fourteen ingredients were selected as the main active compounds, and MY11 might be the most important metabolite in Xihuang pill. PI3K/Akt signaling pathway and receptor tyrosine kinases were considered as crucial targets for Xihuang pill against glioblastoma through KEGG enrichment and CTP analysis. The present experiments indicated that Xihuang pill suppressed the activation of PI3K/Akt/mTOR signaling pathway in glioblastoma cells and mouse xenografts via modulating the expression of PTEN and Rheb proteins, the interaction between TSC2 and Rheb, and the production of PIP3. Meanwhile, after glioblastoma cells treatment with Xihuang pil, the release of IL-1β, INF-γ was increased and the production of IL-10, TGF-β1 was decreased in glioblastoma cells after incubated with Xihuang pill. In addition, the activation of the upstream positive modulators of PI3K/Akt/mTOR pathway including PDGF/PDGFR and FGF/FGFR signaling were down-regulated in glioblastoma cells and mouse xenografts after treatment with Xihuang pill. Taken together, Xihuang pill inhibiting glioblastoma cell growth might be partly through down-regulating the activation of PDGF/PDGFR or FGF/FGFR-PI3K/Akt/mTOR signaling axis and improving immuno-suppressive micro-environment of glioblastoma. [Display omitted] • Glioblastoma with activated RTKs-PI3K/Akt/mTOR signaling has poor prognosis. • Xihuang pill (XHP) has been used for cancer treatment in China since 18th century. • XHP inhibits the activation of PDGF/PDGFR and FGF/FGFR signaling in glioblastoma. • XHP regulates PTEN expression, TSC2-Rheb interaction and PIP3 release in glioblastoma. • XHP induces IL-1β, INF-γ release and reduces IL-10, TGF-β1 production in glioblastoma. [ABSTRACT FROM AUTHOR]

Xihuang pill as a famous traditional Chinese formula has long been used as an adjuvant therapy for cancer. This study is aimed at summarizing recent advances in research of Xihuang pill's anti-cancer efficacies from the theoretical basis of traditional Chinese medicine, pharmacological activities, chemical components and its clinical application. The literature information was obtained from several authoritative databases including PubMed, Embase, Cochrane Library, CNKI and Wan Fang before April 30, 2023. We also analyzed the representatively chemical compounds of Xihuang pill in vivo experiments using HPLC-Q/TOF-MS. The present study indicated that Xihuang pill, a classic anti-tumor prescription, had efficacies of strengthening body resistance, clearing heat and detoxification, and promoting blood circulation for removing blood stasis. Modern basic researches showed that Xihuang pill played anti-cancer roles through inducing cancer cell apoptosis, inhibiting cell proliferation, migration, invasion and angiogenesis, improving immune function and tumor microenvironment, and regulating related signaling pathways. Its chemical components are primarily consisted of amino acids, terpenoids, fatty acids, fatty acid esters, phenolics, bile acids, bile pigments and volatile oil. Clinically, Xihuang pill, as an adjuvant drug for cancer treatment, was mostly combined with chemotherapy, which could prolong survival, enhance response rate, improve patients' life quality, regulate immune function and alleviate chemotherapy-induced toxicities. This present study suggests that Xihuang pill may be a promising adjuvant therapy for cancer, and proposes the possibility of future research directions for Xihuang pill based on the current research status. [Display omitted] • Xihuang pill is a famous TCM formula used as an adjuvant therapy for cancer. • This study first comprehensive summarized Xihuang pill's anti-cancer efficacy. • Xihuang pill could improve the efficacy of west medicine and alleviate toxicities. • Xihuang pill might be a promising adjuvant therapy for cancer. • This study also proposed the future research directions for Xihuang pill. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy and safety of ultrasound-guided local injection of methotrexate (MTX) in the treatment of cesarean scar pregnancy (CSP) diagnosed in the first trimester.Study Design: The clinical and imaging data of 101 CSP patients who received ultrasound-guided local injection of MTX in our hospital between January 2007 and December 2018 were retrospectively analyzed. The decline in serum β human chorionic gonadotropin (βHCG) level, size and blood flow of lesions, vaginal bleeding, liver/kidney functions, and other indicators were observed or tested after treatment on a weekly basis.Results: The duration of amenorrhea was 6.1 ± 0.8 weeks (range: 5.7-8.1 weeks) and the initial serum βHCG level was 20,321 ± 965 U/L in 97 patients, The mean time t to βHCG normalization was 40 ± 14 days (range: 21-140 days), Minor intermittent vaginal bleeding occurred after local MTX injection, lasting 25 ± 17 days (range: 10-61 days), and the lesions at the scar sites had completely disappeared with an average interval of 39 ± 29 days ; The treatment failed in four patients. The average duration of amenorrhea was 7.5 weeks and the average initial serum βHCG level was 91,359 U/L.Conclusion: Ultrasound-guided local injection of MTX is an effective and minimally invasive treatment for CSP. However, it is not feasible for patients with long-term amenorrhea (>8 weeks) and markedly increased blood βHCG level. [ABSTRACT FROM AUTHOR]

Abstract: Aim of study: There are multimodal and multidisciplinary approaches to treat diabetic peripheral neuropathy (DPN). However, the intractable adverse effects limited their widespread use. Chinese herbal medicine (CHM) is increasingly used for the treatment of DPN. The aim of this study was to review existing evidence on the effectiveness of CHM for the treatment of DPN. Materials and methods: Searches were performed with Medline, Embase, Cochrane Central Register of Controlled Trials, CNKI, CBM and Wangfan databases. Controlled trials comparing CHM with other medicine for the treatment of DPN were analyzed. Results: Eighteen trials met the inclusion criteria. All trials used vitamin B12 and/or B1 as control. Clinical therapeutic effect, divided by three grades including marked effective, effective and ineffective according to the improved degree of subjective symptom, tendon reflex, and nerve conduction velocity, was the only end point reported in all trials, and thus evaluated. The results showed CHM treatment was associated with a superiority in marked effective (odds ratio [OR], 2.40; 95% confidence interval [CI]: 0.94 to 2.97; p<0.001), and effective (OR, 1.39; 95% CI: 1.16 to 1.67; p<0.001). Patients who received CHM treatment was associated with a less likely to report ineffective (OR, 0.26; 95% CI: 0.21 to 0.33, p<0.001). No adverse events were reported in any of the included trials. Conclusions: According to the pooled results of our study and the poor quality of the included trials, it might be uncertainty that there was a superiority of CHM for treating DPN. More rigorous controlled trials are required to substantiate or refute these early findings. [Copyright &y& Elsevier]

Chronic kidney disease can be caused by numerous diseases including obesity and hyperuricemia (HUA). Obesity may exacerbate the renal injury caused by HUA. Red ginseng, a steamed products of Panax ginseng Meyer root, is known for its remarkable efficacy in improving metabolic syndrome, such as maintaining lipid metabolic balance. However, the role of red ginseng on hyperuricemia-induced renal injury in obese cases remains unclear. This study aimed to investigate the action of red ginseng extract (RGE) on lipotoxicity-induced renal injury in HUA mice. A high-fat diet (HFD)-induced obesity model was employed to initially investigate the effects of RGE on body weight, TC, OGTT, renal lipid droplets, and renal function indices such as uric acid, creatinine, and urea nitrogen. Renal structural improvement was demonstrated by H&E staining. Subsequently, an animal model combining obesity and HUA was established to further study the impact of RGE on OAT1 and ACC1 expression levels. The mechanisms underlying renal injury regulation by RGE were postulated on the basis of RNA sequencing, which was verified by immunohistochemical (including F4/80, Ki67, TGF-β1, α-SMA, and E-cadherin), Masson, and Sirius red staining. RGE modulated HFD-induced weight gain, glucose metabolism, and abnormalities of uric acid, urea nitrogen, and creatinine. RGE alleviated the more severe renal histopathological changes induced by obesity combined with HUA, with down-regulated the protein levels of ACC1, F4/80, Ki67, TGF-β1, and α-SMA, and up-regulated OAT1 and E-cadherin. RGE has ameliorative effects on chronic kidney disease caused by obesity combined with HUA by maintaining lipid balance and reducing renal inflammation and fibrosis. [Display omitted] • RGE improved metabolic disorders and renal injury induced by obesity and obesity combination with hyperuricemia. • RGE ameliorated obesity-induced lipid accumulation in the kidney. • RGE improved renal inflammation and fibrosis exacerbated by lipotoxicity. [ABSTRACT FROM AUTHOR]

• It is confirmed for the first time that valproic acid has a harmful effect on the stability of titanium implant under the condition of osteoporosis. • Studies have confirmed that simvastatin can reverse the osseointegration of titanium implants treated with valproic acid in the state of osteoporosis. • It is confirmed that valproic acid can inhibit the proliferation and differentiation of osteoblasts, while simvastatin can reverse the harmful effect of valproic acid on osteoblasts. The present work was aimed to evaluate the effect of valproic acid(VPA), simvastatin (SIM)+VPA on Ti(titanium) rods osseointegration in ovariectomized(OVX) rats and further investigation of the possible mechanism. The MC3T3-E1 cells were co-cultured with VPA, SIM + VPA and induced to osteogenesis, and the cell viability, mineralization ability were observed by MTT and ALP staining, Alizarin Red staining and Western blotting. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: group OVX and VPA, SIM + VPA, and all the rats received Ti implants and animals belong to group VPA, SIM + VPA received valproic acid(300 mg/kg/day), valproic acid(300 mg/kg/day) plus SIM (25 mg/kg/day), respectively, treatment until death at 12 weeks. Micro-CT, histology, biomechanical testing, bone metabolism index and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to observe the therapeutic effect and explore the possible mechanism. Results shown that VPA decreased new bone formation around the surface of titanium rods and push-out force other than group OVX. Histology, Micro-CT and biochemical analysis results showed combined application of systemic VPA showed harmful effects than OVX group on bone formation in osteopenic rats, with the worse effects on CTX-1, P1NP and microarchitecture as well as biomechanical parameters by down-regulated gene expression of Runx2, OCN, Smad1, BMP-2 and OPG, while up-regulated RANKL. However, after SIM treatment, the above indicators were significantly improved. The present study suggests that systemic use of VPA may bring harm to the stability of titanium implants in osteoporosis, SIM can reverse the negative effect of VPA on the osseointegration of titanium rods in ovariectomized rats. [ABSTRACT FROM AUTHOR]

A widely used traditional prescription, Yi-Gan San (YGS) is a remedy for neurodegenerative disorders. The formulation consists of seven Chinese medicinal materials in specific proportions, namely Uncariae Ramulus cum Uncis (Uncaria rhynchophylla (Miq.) Miq. ex Havil.), Bupleuri Radix (Bupleurum chinense DC.), Angelicae Sinensis Radix (Angelica sinensis (Oliv.) Diels), Chuanxiong Rhizoma (Ligusticum wallichii Franch.), Poria (Poria cocos (Schw.) Wolf), Atractylodis Macrocephalae Rhizoma (Atractylodes macrocephala Koidz.) and Glycyrrhizae Radix et Rhizoma (Glycyrrhiza uralensis Fisch.). Using YGS has been shown to alleviate various behavioural and psychological symptoms of dementia (BPSD). The goal of this review is to give up-to-date information about the traditional uses, chemistry, pharmacology and clinical efficacy of YGS based on the scientific literature and to learn the current focus and provide references in the next step. The database search room was accessed using the search terms "Yi-Gan San" and "Yokukansan" to obtain results from resources such as Web of Science, PubMed, Google Scholar and Sci Finder Scholar. We not only consulted the literature of fellow authors for this review but also explored classical medical books. YGS has been used to cure neurosis, sleeplessness, night weeping and restlessness in infants. Its chemical components primarily consist of triterpenes, flavonoids, phenolics, lactones, alkaloids and other types of compounds. These active ingredients displayed diverse pharmacological activities to ameliorate BPSD by regulating serotonergic, glutamatergic, cholinergic, dopaminergic, adrenergic, and GABAergic neurotransmission. In addition, YGS showed neuroprotective, antistress, and anti-inflammatory effects. The majority of cases of neurodegenerative disorders are treated with YGS, including Alzheimer's disease and dementia with Lewy bodies. Based on previous studies, YGS has been used as a traditional prescription in East Asia, such as Japan, Korea and China, and it has diverse chemical compounds and multiple pharmacological activities. Nevertheless, few experimental studies have focused on chemical and quantitative YGS studies, suggesting that further comprehensive research on its chemicals and quality assessments is critical for future evaluations of drug efficacy. [Display omitted] • Traditional uses, chemical compounds, pharmacological activities and clinical studies of Yi-Gan San (YGS) were concluded. • The research status about the traditional uses of YGS was presented in this review. • All know chemical constituents isolated from YGS and their chemical structures were proposed in this review. • The research on pharmacological effects and underlying mechanisms of YGS were summarized. • The clinical curative effects of YGS were outlined in detail. [ABSTRACT FROM AUTHOR]

Nanoparticle mediated photothermal ablation of cancerous tissue shows promising results and applicability as a highly efficacious treatment method. As a majority of the photothermal work has been conducted with minimal attenuation of the laser before reaching the nanoparticles within surface seeded tumors in-vivo or through buffered media in-vitro , it is important to understand the effects of greater laser attenuation on photothermal efficacy mediated by changes in the scattering and absorption of the laser. Photothermal efficacy using a near infrared (NIR) 785 nm laser irradiating polystyrene (PS) stabilized magnetite (Fe 3 O 4 ) nanoparticles (PS-Fe 3 O 4 ) is examined on MDA-MB-231 human mammary gland adenocarcinoma in-vitro . Agarose gel columns of various heights were created to simulate soft tissue and subsequently used for NIR laser attenuation. Polystyrene was found to significantly improve magnetite nanoparticle stability in serum containing media and modified Hank's Balanced Salt Solution and was able to induce significant hyperthermic ablation at mass concentrations which also did not elicit significant innate toxicity. Furthermore it was found that the polystyrene coating significantly reduced innate toxicity over 48 h compared to uncoated magnetite. Agar gel layers provided similar optical attenuation in the NIR region to skin and prostate. [ABSTRACT FROM AUTHOR]

Xiaojin Pills is a classic prescription for the treatment of mammary glands hyperplasia with a history of nearly 300 years, and is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinic. Clinical and animal studies have shown that Xiaojin Pills has the effects of anti-mammary glands hyperplasia, promoting blood circulation, anti-inflammation and analgesia. However, its initial administration method was "taking orally after soaked with Chinese Baijiu", the modern method was changed to "taking orally with water" in recent 20 years. Whether there is any difference in the efficacy of the two administration methods is still unknown. To reveal the difference in efficacy and metabolic mechanism of anti-mammary gland hyperplasia between the oral administration of Xiaojin Pills accompanied with Chinese Baijiu (XJP&B) and water (XJP&W). COX-2 inhibition rate test and anti-platelet aggregation activity test were used to investigate the efficacy difference between the 40 vol% Chinese Baijiu and water extracts of Xiaojin Pills on anti-inflammatory and blood-activating in vitro. Kunming male mice (20 ± 5 g) and SD female rats (200–220 g) were orally treated with XJP&B and XJP&W, respectively. Then the difference in anti-inflammatory and analgesic effects between XJP&B and XJP&W were evaluated via xylene-induced ear swelling test, formaldehyde-induced pain test, and acetic acid-induced writhing test in mice. Determination of nipple diameter, pathological examination of mammary gland tissue, determination of serum E 2 , P and FSH content and hemorheological parameters of rats with mammary gland hyperplasia were performed to explore the efficacy difference in anti-mammary gland hyperplasia between XJP&B and XJP&W. Metabolomics was used to study the difference of anti-mammary gland hyperplasia mechanism between XJP&B and XJP&W. The results showed that the effect of XJP&B was superior to that of XJP&W in anti-platelet aggregation, inhibition of inflammation and pain, and anti-mammary gland hyperplasia. Interestingly, the advantages were more significant under low-dose condition. In addition, the mechanism of the two combinations against mammary gland hyperplasia was indeed different. Their common metabolic pathways include tryptophan metabolism and alanine, aspartic acid and glutamic acid metabolism. However, Chinese Baijiu and XJP&B also have additional regulatory effects on linoleic acid metabolic pathway. In brief, this research demonstrated that the efficacy of XJP&B was better than that of XJP&W in activating the blood, anti-inflammation, analgesia and anti-mammary gland hyperplasia, which means that XJP&B has synergistic and superior effects. The special dose-effect relationship under the condition of XJP&B was also found, laying the foundation for clinical treatment to reduce the dosage and shorten the medication cycle, which is beneficial to reduce the economic burden of patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) play an important role in tumor metastasis and may be a target for metastasis prevention. The traditional Chinese medicine Jinfukang functions to improve immunity, prevent metastasis, and prolong lung cancer patient survival periods. Yet, whether Jinfukang prevents metastasis by regulating immune cells to clearance CTCs is still unknown. To explore the anti-metastasis mechanism of Jinfukang from the perspective of regulating NK cells to clear CTCs. CTC-TJH-01 cell was treated with Jinfukang. Cytokine chip was used to detect cytokines in cell culture supernatant. Lymphocyte recruitment assay was detected by Transwell and flow cytometry. Protein expression was analysis by Western blot. LDH kit was used to detect cytotoxicity. NOD-SCID mice used for tail vein injection to study lung metastasis. Jinfukang could promote the expression and secretion of the chemokine CX3CL1 by CTCs. In addition, Jinfukang could promote the recruitment of natural killer (NK) cells by CTCs and significantly increase the cytotoxic effect of NK cells on CTCs. Moreover, Jinfukang could upregulate the expression of FasL and promote the secretion of TNF-α by NK cells and that NK cells could induce the apoptosis of CTCs through the Fas/FasL signaling pathway. Finally, we confirmed that Jinfukang could promote NK cells to kill CTCs and then inhibit lung cancer metastasis in vivo. The above effects of Jinfukang could be partially reversed by an anti-CX3CL1 mAb. These results suggest that Jinfukang may prevent lung cancer metastasis by enhancing the clearance of CTCs in the peripheral blood by NK cells, providing evidence for the anti-metastasis effect of Jinfukang. [Display omitted] [ABSTRACT FROM AUTHOR]

Tripterygium wilfordii Hook F. (TwHF), a traditional Chinese herb medicine, has been widely used for clinical treatment of various rheumatic immune diseases. Tripterygium glycosides (TG) extracted from TwHF has been verified to process multiple bioactivities, including immunosuppressive, anti-inflammatory and anti-cancer effects. However, the clinical application of TG is limited due to its severe toxicity and narrow therapeutic window. For the clinical safety of TG usage, attenuation of toxicity is the key issue to be solved. Tripterygium glycoside fraction n2 (TG-n2) is a detoxified mixture obtained from TG using a new preparation method. In our previous study, we have demonstrated that TG-n2 has a lower toxicity than TG. The aim of the present study was to screen the renal protective effect of TG-n2 in nephrotic syndrome (NS) induced by adriamycin (ADR) in rats and its effect on apoptosis, as well as the effective difference between TG-n2 and TG. The ADR-induced NS rat model was established. Rats were intravenously injected with ADR (6 mg/kg), then treated with either TG-n2 (10 mg/kg/day) or TG (10 mg/kg/day) by oral gavage for 4 weeks. Clinical indexes in each group were determined. HE staining and electron microscopic analysis were used to evaluate renal histopathological damage. Caspase-3 activity reagent and TUNEL staining were used to estimate renal apoptosis. Protein levels of caspase-3, caspase-9, caspase-8, caspase-12, Bax, Bcl-2, p53, TNF-R1, FLIP and podocin were measured by Western Blot. TG-n2 and TG intervention ameliorated renal function as assessed by the levels of 24-h proteinuria, Cr, BUN, TC, TG, ALB and LDL-c. TG-n2 and TG alleviated the decrease of podocin protein expression and morphological injury of podocyte as screened by Western Blot and electron microscopic analysis. Besides, renal tubular injury was reduced as inspected by light microscopic analysis. TG-n2 and TG could significantly inhibit the apoptosis and activity of caspase-3 in kidney tissues as examined by fluorescence microscopic analysis and reagent. After intervention of TG-n2 and TG, protein levels of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax, p53 and TNF-R1 in renal issues were significantly decreased compared with ADR group. In contrast, protein level of Bcl-2 was elevated remarkedly. Our data suggested that attenuated TG-n2 may have a similar protective effect with TG in ADR-induced NS in rats by inhibiting activation of apoptosis. Image 1 • First report on protective effect of Tripterygium glycoside fraction n2 in adriamycin-induced nephrotic syndrome in rats. • Apoptosis was adaptively reduced by treatment of Tripterygium glycoside fraction n2. • Tripterygium glycoside fraction n2 shares similar curative effect of nephrotic syndrome with Tripterygium glycosides. [ABSTRACT FROM AUTHOR]