[Mechanism of Shenling Baizhu Powder on treatment of alcoholic liver disease by regulating TLR4/NLRP3 pathway].

This study aims to investigate the regulatory effects of Shenling Baizhu Powder(SBP) on cellular autophagy in alcoholic liver disease(ALD) and its intervention effect through the TLR4/NLRP3 pathway. A rat model of chronic ALD was established by gavage of spirits. An ALD cell model was established by stimulating BRL3A cells with alcohol. High-performance liquid chromatography(HPLC) was utilized for the compositional analysis of SBP. Liver tissue from ALD rats underwent hematoxylin-eosin(HE) and oil red O staining for pathological evaluation. Enzyme-linked immunosorbent assay(ELISA) was applied to quantify lipopolysaccharides(LPS), tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1ß), and interleukin-18(IL-18) levels. Quantitative reverse transcription polymerase chain reaction(qRT-PCR) was conducted to evaluate the mRNA expression of myeloid differentiation factor 88(MyD88) and Toll-like receptor 4(TLR4). The effect of different drugs on BRL3A cell proliferation activity was assessed through CCK-8 analysis. Western blot analysis was performed to examine the protein expression of NOD-like receptor pyrin domain-containing 3(NLRP3), nuclear factor-kappa B P65(NF-κB P65), phosphorylated nuclear factor-kappa B P65(p-P65), caspase-1, P62, Beclin1, and microtubule-associated protein 1 light chain 3(LC3Ⅱ). The results showed that SBP effectively ameliorated hepatic lipid accumulation, reduced liver function, mitigated hepatic tissue inflammation, and reduced levels of LPS, TNF-α, IL-1ß, and IL-18. Moreover, SBP exhibited the capacity to modulate hepatic autophagy induced by prolonged alcohol intake through the TLR4/NLRP3 signaling pathway. This modulation resulted in decreased expression of LC3Ⅱ and Beclin1, an elevation in P62 expression, and the promotion of autolysosome formation. These research findings imply that SBP can substantially enhance liver function and mitigate lipid irregularities in the context of chronic ALD. It achieves this by regulating excessive autophagic responses caused by prolonged spirit consumption, primarily through the inhibition of the TLR4/NLRP3 pathway.

Association of 25-hydroxyvitamin D levels with lipid profiles in osteoporosis patients: a retrospective cross-sectional study.

BACKGROUND: In the literature, scarce data investigate the link between 25-hydroxyvitamin D (25[OH]D) and blood lipids in the osteoporosis (OP) population. 25(OH)D, as a calcium-regulating hormone, can inhibit the rise of parathyroid hormone, increase bone mineralization to prevent bone loss, enhance muscle strength, improve balance, and prevent falls in the elderly. This retrospective cross-sectional study aimed to investigate the association between serum 25(OH)D levels and lipid profiles in patients with osteoporosis, with the objective of providing insight for appropriate vitamin D supplementation in clinical settings to potentially reduce the incidence of cardiovascular disease, which is known to be a major health concern for individuals with osteoporosis. METHODS: This is a retrospective cross-sectional study from the Affiliated Kunshan Hospital of Jiangsu University, including 2063 OP patients who received biochemical blood analysis of lipids during hospitalization from January 2015 to March 2022. The associations between serum lipids and 25(OH)D levels were examined by multiple linear regression. The dependent variables in the analysis were the concentrations of serum lipoprotein, total cholesterol (TC), triglycerides (TGs), apolipoprotein-A, lipoprotein A, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (LDL-C). The independent variable was the concentration of blood serum 25(OH)D. At the same time, age, body mass index, sex, time and year of serum analysis, primary diagnosis, hypertension, diabetes, statins usage, beta-C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide were covariates. Blood samples were collected in the early morning after the overnight fasting and were analyzed using an automated electrochemiluminescence immunoassay on the LABOSPECT 008AS platform (Hitachi Hi-Tech Co., Ltd., Tokyo, Japan). The generalized additive model was further applied for nonlinear associations. The inception result for smoothing the curve was evaluated by two-piecewise linear regression exemplary. RESULTS: Our results proved that in the OP patients, the serum 25(OH)D levels were inversely connected with blood TGs concentration, whereas they were positively associated with the HDL, apolipoprotein-A, and lipoprotein A levels. In the meantime, this research also found a nonlinear relationship and threshold effect between serum 25(OH)D and TC, LDL-C. Furthermore, there were positive correlations between the blood serum 25(OH)D levels and the levels of TC and LDL-C when 25(OH)D concentrations ranged from 0 to 10.04 ng/mL. However, this relationship was not present when 25(OH)D levels were higher than 10.04 ng/mL. CONCLUSIONS: Our results demonstrated an independent relationship between blood lipids and vitamin D levels in osteoporosis patients. While we cannot establish a causal relationship between the two, our findings suggest that vitamin D may have beneficial effects on both bone health and blood lipid levels, providing a reference for improved protection against cardiovascular disease in this population. Further research, particularly interventional studies, is needed to confirm these associations and investigate their underlying mechanisms.

Discovery of Novel Chinese Medicine Compounds Targeting 3CL Protease by Virtual Screening and Molecular Dynamics Simulation.

The transmission and infectivity of COVID-19 have caused a pandemic that has lasted for several years. This is due to the constantly changing variants and subvariants that have evolved rapidly from SARS-CoV-2. To discover drugs with therapeutic potential for COVID-19, we focused on the 3CL protease (3CLpro) of SARS-CoV-2, which has been proven to be an important target for COVID-19 infection. Computational prediction techniques are quick and accurate enough to facilitate the discovery of drugs against the 3CLpro of SARS-CoV-2. In this paper, we used both ligand-based virtual screening and structure-based virtual screening to screen the traditional Chinese medicine small molecules that have the potential to target the 3CLpro of SARS-CoV-2. MD simulations were used to confirm these results for future in vitro testing. MCCS was then used to calculate the normalized free energy of each ligand and the residue energy contribution. As a result, we found ZINC15676170, ZINC09033700, and ZINC12530139 to be the most promising antiviral therapies against the 3CLpro of SARS-CoV-2.

Treatment strategies and pharmacist-led medication management for Helicobacter pylori infection.

Half of the world's population is Helicobacter pylori carrier. Updated guidelines and consensus have been issued across regions with the main aim of reducing social transmission and increasing H. pylori eradication rate. Although alternative therapies including traditional Chinese medicine and probiotics have also been used to improve H. pylori eradication rate in clinical practice, current mainstream treatment is still dependent on triple and quadruple therapies that includes antibacterial agents (e.g., amoxicillin and furazolidone) and proton pump inhibitor. Researches also assessed the eradication rate of optimized high-dose dual therapy in treating H. pylori infection. With the increase of antibiotic resistance rate, the treatment strategies for H. pylori infection are constantly adjusted and improved. Besides, low medication compliance is another key influencing factor for H. pylori treatment failure. Emerging studies indicate that pharmacists' intervention and new pharmaceutical care methods can enhance patient medication compliance, reduce adverse drug reactions, and improve H. pylori eradication rate. The purpose of this review is to summarize the advances in treating H. pylori infection and highlight the necessity of developing novel strategies to cope with the increasing challenges and to achieve personalized medication. Also, this review attaches great importance to pharmacists in optimizing H. pylori treatment outcomes as a routine part of therapy.

Association between vitamin D and zoledronate-induced acute-phase response fever risk in osteoporotic patients.

Objectives: To elucidate the independent correlation between vitamin D content and zoledronate (ZOL)-triggered acute-phase response (APR) fever risk in osteoporotic (OP) patients, and to examine the potential threshold for optimal vitamin D concentrations that prevent the occurrence of ZOL-induced fever. Methods: This retrospective investigation was based on a prospectively documented database compiled at the Affiliated Kunshan Hospital of Jiangsu University between January 2015 and March 2022. In total, 2095 OP patients, who received ZOL during hospitalization, were selected for analysis. The primary endpoint was the presence (>37.3°C) or absence (≤37.3°C) of fever, quantified by the maximum body temperature, measured within 3 days of ZOL infusion. The exposure variable was the baseline serum 25-hydroxyvitamin D (25[OH]D) levels. Results: The OP patients with fever exhibited markedly reduced 25(OH)D content than those without fever. Upon adjusting for age, gender, order of infusion of ZOL, main diagnosis, season of blood collection, year of blood collection, calcitonin usage, and beta-C-terminal telopeptide of type I collagen (ß-CTX) levels, a 10 ng/mL rise in serum 25(OH)D content was correlated with a 14% (OR, 0.86; 95% CI, 0.76 to 0.98, P-value = 0.0188) decrease in the odds of ZOL-induced fever. In addition, a non-linear relationship was also observed between 25(OH)D levels and fever risk, and the turning point of the adjusted smoothed curve was 35 ng/mL of serum 25(OH)D content. Conclusions: Herein, we demonstrated the independent negative relationship between serum 25(OH)D content and ZOL-induced fever risk. According to our analysis, 25(OH)D above 35 ng/mL may be more effective in preventing ZOL-induced APR. If this is confirmed, a "vitamin D supplemental period" is warranted prior to ZOL infusion, particularly the first ZOL infusion, to ensure appropriate 25(OH)D levels that protect against ZOL-induced fever.

[Pharmacodynamic material basis and anti-inflammatory mechanism of Chrysanthemum morifolium cv. Fubaiju based on UPLC-Q-TOF-MS/MS combined with network pharmacology].

The chemical components in rats after oral administration of the water extract of Chrysanthemum morifolium cv. Fubaiju(CMF) were analyzed by UPLC-Q-TOF-MS/MS technique. Forty-four compounds were identified from the water extract of CMF and 11 components were identified from the rat serum. A total of 264 potential anti-inflammatory targets were identified by network pharmacology based on serum components. The "component-target" network and protein-protein interaction(PPI) network were constructed, and GO function enrichment and KEGG pathway enrichment analyses were performed. The molecular docking was carried out to validate the results of network pharmacology. The results showed that CMF might act on AKT1, TNF, TP53, IL6, INS, and other core targets through apigenin, luteolin, acacetin, diosmetin, 3,4-O-dicaffeoylquinic acid, and other active components, and exert anti-inflammatory effects by regulating PI3 K-AKT signaling pathway, FoxO signaling pathway, cAMP signaling pathway, Ras signaling pathway, and other pathways. The pharmacodynamic materials basis of CMF was identified by UPLC-Q-TOF-MS/MS technology, and the core anti-inflammatory targets and the underlying mechanism of action were analyzed by network pharmacology and molecular docking, which provided a reference for comprehensively clarifying the pharmacodynamic materials basis and quality control of CMF.

Gingko biloba-inspired lactone prevents osteoarthritis by activating the AMPK-SIRT1 signaling pathway.

BACKGROUND: Uncoupled extracellular matrix (ECM) causes cartilage degeneration and osteoarthritis (OA) by suppressing the synthesis and activating the degradation of ECM components. Gingko biloba is a natural Chinese herb with a variety of biological functions; however, the extent to which it can protect against OA and the mechanisms involved are unknown. METHODS: In our study, using bioinformatics tools, we were able to identify an important lactone, bilobalide (BB), from Gingko biloba. In vitro experiments were performed to evaluate the potential therapeutic effects of BB on ECM homeostasis. In vivo experiments were conducted to assess the protection of systemic administration of BB on cartilage degeneration. Molecular mechanisms underlying BB-regulated anti-arthritic role were further explored. RESULTS: In interleukin-1ß-incubated human chondrocytes, in vitro treatment with BB increased the expression of cartilage anabolic proteins, while inhibiting the activities of ECM degrading enzymes. In a mice model, systemic administration of BB, in vivo, prevented post-traumatic cartilage erosion and attenuated the formation of abnormal osteophytes in the subchondral bone. Mechanistically, the activation of the adenosine 5'-monophosphate-activated protein kinase (AMPK)-sirtuin 1 (SIRT1) signaling pathway was involved in the anti-arthritic effects of BB. In vitro, blocking BB's chondroprotection with the AMPK-specific inhibitor Compound C abrogated it. CONCLUSIONS: These results demonstrated that BB extracted from Gingko biloba regulates ECM balance to prevent OA by activating the AMPK-SIRT1 signaling pathway. This study proposed the monomer BB, a traditional Chinese medicine, as a de novo therapeutic insight for OA. Schematic representation of the experimental design. Based on the bioinformatic analysis, bilobalide (BB), a natural herb Gingko biloba-derived ingredient, was identified as a candidate for treating osteoarthritis. In vitro, BB treatment not only facilitates cartilage extracellular matrix synthesis but also inhibits proteolytic enzyme activities. In vivo intraperitoneal injection of BB improves cartilage degeneration and subchondral bone sclerosis. BB, in particular, had anti-arthritic effects by activating the AMPK-SIRT1 signaling pathway.

Remove Non-hydrated Phospholipids in Okra Seed Oil by Silicon Dioxide.

Water degumming, mainly removes hydrated phospholipids, is the most common method applying in traditional edible oil production. Silicon dioxide (SiO2) adsorption has been proved as a green and efficient method for removing phospholipids from rapeseed oil. But both methods exhibited poor effect on okra seed oil. Based on a hypothesis that SiO2 can adsorb non-hydrated phospholipids, removal effect of non-hydrated phospholipids in okra seed oil was studied. Single factor test and response surface design were used to optimize the SiO2 adsorbing process in water-degummed oil. Meanwhile, the qualities and flavor changes of okra seed oil before and after degumming were compared and analyzed. The results showed that the optimized degumming procedure was: 1.43% (w/w) of SiO2 added into the water-degummed oil, and the mixture was stirred at 33.52℃ for 30.47 min. The maximum non-hydrated phospholipids removal rate reached 43.3%. Comparing with crude okra seed oil, the optimal degumming method resulted in the increase of peroxide value and the decrease of induction period (IP) of the oil. However, it had the same safety as the water and the SiO2 degumming methods. It could retain 62% of total phenols, which was less than the water and the SiO2 degumming methods (both about 79%). The differences of E-nose sensors among oils were most likely caused by the pyrazines. It is necessary to study the composition and properties of phospholipids and develop new methods to further improve the phospholipids removal rate of okra seed oil.

Combinatory therapy of MRP1-targeted photoimmunotherapy and liposomal doxorubicin promotes the antitumor effect for chemoresistant small cell lung cancer.

Small cell lung cancer (SCLC), considered a mortal recalcitrant cancer, is a severe healthcare issue because of its poor prognosis, early metastasis, drug resistance and limited clinical treatment options. In our previous study, we established a MRP1-targeted antibody-IR700 system (Mab-IR700) for near infrared photoimmunotherapy (NIR-PIT) which exhibited a promising therapeutic effect on drug resistant H69AR cells both in vitro and in vivo, though the tumor growth suppression effect did not last long with a single round of PIT treatment. To achieve a better anticancer effect, we have combined Mab-IR700-mediated NIR-PIT with liposomal doxorubicin (Doxil®) and investigated the in vitro and in vivo cytotoxicity by using a H69AR/3T3 cell co-culture model in which 3T3 cells were used to mimic stromal cells. Cytotoxicity experiments demonstrated the specificity of Mab-IR700 to H69AR cells, while cytotoxicity and flow cytometry experiments confirmed that H69AR cells were doxorubicin-resistant. Compared with Mab-IR700-mediated PIT or Doxil-mediated chemotherapy, the combination therapy exhibited the best cell killing effect in vitro and superior tumor growth inhibition and survival prolongation effect in vivo. Super enhanced permeability and retention (SUPR) effect was observed in both co-culture spheroids and tumor-bearing mice. Owing to an approximately 9-fold greater accumulation of Doxil within the tumors, NIR-PIT combined with Doxil resulted in enhanced antitumor effects compared to NIR-PIT alone. This photoimmunochemotherapy is a practical strategy for the treatment of chemoresistant SCLC and should be further investigated for clinical translation.

Microwave ablation combined with lipiodol-microsphere mixed or conventional transarterial chemoembolization for the treatment of colorectal liver metastases: A retrospective study.

PURPOSE: To investigate the clinical outcomes of microwave ablation (MWA) combined with lipiodol-microsphere mixed transarterial chemoembolization (mTACE) or conventional TACE (cTACE) for patients with colorectal liver metastases (CRLM). MATERIALS AND METHODS: This retrospective study evaluated the medical records of patients with CRLM who underwent MWA combined with mTACE or cTACE from January 2018 to September 2021. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated during the follow-up. In addition, prognostic factors affecting survival were analyzed by univariate and multivariate methods. RESULTS: A total of 79 patients with CRLM were enrolled in the study (MWA-mTACE group, n = 38; MWA-cTACE group, n = 41). The patients who underwent MWA-mTACE had higher DCR (86.8% vs. 65.9%, P = 0.029) and better PFS (median, 8.1 vs. 5.5 months, P = 0.018) than those who underwent MWA-cTACE, but no significant difference was found in ORR (34.2% vs. 22.0%, P = 0.225) and OS (median, 15.7 vs. 13.0 months, P = 0.231). Further univariate and multivariate analyses indicated that MWA-mTACE was an independent positive factor for PFS, and abnormal carcinoembryonic antigen level was a hazard factor for OS. The postoperative laboratory tests and complications in patients who underwent MWA-mTACE were similar to those who underwent MWA-cTACE. CONCLUSION: Lipiodol-microsphere mixed TACE might be an effective and safe treatment to combine with microwave ablation for patients with colorectal liver metastases.

Arctiin-reinforced antioxidant microcarrier antagonizes osteoarthritis progression.

Loss of extracellular matrix (ECM) of cartilage due to oxidative stress injury is one of the main characteristics of osteoarthritis (OA). As a bioactive molecule derived from the traditional Chinese Burdock, arctiin exerts robust antioxidant properties to modulate redox balance. However, the potential therapeutic effects of arctiin on OA and the underlying mechanisms involved are still unknown. Based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) tool, Burdock-extracted small molecule arctiin was identified as a potential anti-arthritic component. In vitro, treatment using arctiin rescued the interleukin (IL)-1ß-induced activation of proteinases and promoted the cartilage ECM synthesis in human chondrocytes. In vivo, intraperitoneal injection of arctiin ameliorated cartilage erosion and encountered subchondral bone sclerosis in the post-traumatic OA mice. Transcriptome sequencing uncovered that arctiin-enhanced cartilage matrix deposition was associated with restricted oxidative stress. Mechanistically, inhibition of nuclear factor erythroid 2-related factor 2 (NRF2) abolished arctiin-mediated anti-oxidative and anti-arthritic functions. To further broaden the application prospects, a gellan gum (GG)-based bioactive gel (GG-CD@ARC) encapsulated with arctiin was made to achieve long-term and sustained drug release. Intra-articular injection of GG-CD@ARC counteracted cartilage degeneration in the severe (12 weeks) OA mice model. These findings indicate that arctiin may be a promising anti-arthritic agent. Furthermore, GG-modified bioactive glue loaded with arctiin provides a unique strategy for treating moderate to severe OA.

Mechanism of Ba Zhen Tang Delaying Skin Photoaging Based on Network Pharmacology and Molecular Docking.

Purpose: To study the efficacy of Ba Zhen Tang in delaying skin photoaging and its potential mechanism based on network pharmacology and molecular docking. Methods: First, we screened the active components and targets of Ba Zhen Tang by Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and The Universal Protein Resource (UniProt). The target genes of skin photoaging were obtained from GeneCards and GeneMap database. Then, we analyzed the protein-protein interaction (PPI) by STRING database. The network map was constructed by Cytoscape. Finally, we performed Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis by Metascape database. The molecular docking via Autodock Vina and Pymol. Furthermore, skin photoaging cellular models were established, and the effects of Ba Zhen Tang on ameliorating skin photoaging were investigated. Results: A total of 160 active ingredients in Ba Zhen Tang and 60 targets of Ba Zhen Tang for delaying skin photoaging were identified. By GO enrichment analysis, 1153 biological process entries, 45 cellular component entries and 89 molecular functional entries were obtained. A total of 155 signal pathways were obtained by KEGG analysis. Ba Zhen Tang is related to MAPK signaling pathway, TNF signaling pathway and AGE-RAGE signaling pathway in diabetic complications, etc., which directly affect the key nodes of photoaging. The molecular docking results showed that there was a certain affinity between the main compounds (kaempferol, quercetin, ß-sitosterol, naringenin) and core target genes (PTGS2, CASP3, MAPK1, MAPK3, TP53). Ba Zhen Tang-treated mouse serum inhibited the senescence and p16INK4a expression of human immortalized keratinocyte (HaCaT) cells irradiated by ultraviolet-B (UVB). Conclusion: Our study elucidated the potential pharmacological mechanism of Ba Zhen Tang in the treatment of photoaging through multiple targets and pathways. The therapeutic effects of Ba Zhen Tang on skin photoaging were validated in cellular models.

A network pharmacology-based study of the potential targets and mechanisms of action of Qibao Meiran Dan in delaying skin aging.

OBJECTIVE: The aim of this study was to use network pharmacology to explore the potential targets and mechanisms of action of Qibao Meiran Dan in relation to delaying skin aging. METHODS: The traditional Chinese medicine systems pharmacology database and analysis platform, and the traditional Chinese medicine integrated database, were used to screen the active ingredients and targets of Qibao Meiran Dan. The human gene database GeneCards and the gene database of the National Center for Biotechnology Information were jointly adopted to obtain skin aging-related target genes. The search tool for the retrieval of interacting genes/proteins (STRING) database was used for core analysis of protein-protein interaction. RESULTS: In total, 72 effective active ingredients, 273 action targets, 234 skin aging target genes, and 64 intersecting core targets were identified. GO enrichment analysis provided 393 biological process entries, and the KEGG analysis was represented by the tumor necrosis factor (TNF) signaling pathway, where the core targets of TNF-α and matrix metalloproteinase-1 (MMP-1) were enriched. The experimental results showed that cell morphology was clearer and more refractive in the Qibao Meiran Dan group than in the model group. CONCLUSION: Qibao Meiran Dan may regulate oxidative stress injury and collagen metabolism by downregulating the expression of TNF-α and MMP-1, thus slowing skin aging.

Rare cytochalasans isolated from the mangrove endophytic fungus Xylaria arbuscula.

Four new cytochalasans, arbuschalasins A-D (1-4), along with thirteen known analogues (5-17), were isolated from the solid rice medium of endophytic fungus Xylaria arbuscula. Arbuschalasins A-B feature a rare 5/6/6/6 fused ring system while arbuschalasin D was characterized as the first example of natural cytochalasans that possesses a 5/5/11 fused scaffold. The structures of 1-4 were assigned by spectroscopic data, with their absolute structures being determined by electronic circular dichroism (ECD) calculations. All of the isolates were evaluated against the human colorectal adenocarcinoma cell lines (HCT15). Compounds 6 and 7 showed significant inhibitory effects (IC50 values were 13.5 and 13.4 µM, respectively), being more active than those of the positive control, fluorouracil (103.1 µM).

[Advances of using photoimmunotherapy for anticancer treatment].

Photoimmunotherapy (PIT) is an emerging tumor-targeted phototherapy that combines the tumor specificity of monoclonal antibodies with the phototoxicity of light absorbers to rapidly and selectively induce the immunogenic death of target tumor cells. PIT has minimal side effects due to its high specificity. The immunogenic cell death induced by PIT results in rapid maturation of immature dendritic cells proximal to dying tumor cells. Subsequently, the mature dendritic cells present the tumor antigens to CD8+ T cells and induce their activation and proliferation, thus enhancing the antitumor immune response of the host. PIT can also improve the anticancer efficacy by enhancing the penetration of nanomedicines into tumor tissues. In view of the excellent application prospects of PIT, this review summarizes the advances in the immune activation mechanism of PIT, the superenhanced permeability and retention effect, and the new strategies for combinatory therapy, providing references for future research and clinical translation.

MRP1-targeted near infrared photoimmunotherapy for drug resistant small cell lung cancer.

Small cell lung cancer (SCLC), one of the most aggressive cancers, has a high mortality rate and poor prognosis, and the clinical therapeutic outcomes of multidrug resistant SCLC are even worse. Multidrug resistance protein 1 (MRP1), one of the ATP-binding cassette (ABC) transporter proteins that cause decreased drug accumulation in cancer cells, is overexpressed in drug resistant SCLC cells and could be a promising target for treating the patients suffering from this illness. Near infrared photoimmunotherapy (NIR-PIT) is a newly developed approach for targeted cancer treatment which uses a conjugate of a monoclonal antibody and photoabosorber IR700 followed by NIR light irradiation to induce rapid cancer cell death. In the present study, an anti-MRP1 antibody (Mab) -IR700 conjugate (Mab-IR700) was synthesized, purified and used to treat chemoresistant SCLC H69AR cells that overexpressed MRP1, while non-MRP1-expressing H69 cells were used as a control. Then, the photokilling and tumor suppression effect were separately evaluated in H69AR cells both in vitro and in vivo. Higher cellular delivery of Mab-IR700 was detected in H69AR cells, whereas there was little uptake of IgG-IR700 in both H69 and H69AR cells. Due to the targeting activity of Mab, stronger photokilling effect was found both in H69AR cells and spheroids treated with Mab-IR700, while superior tumor suppression effect was also observed in the mice treated with Mab-IR700 and light illumination. Photoacoustic imaging results proved that oxygen was involved in NIR-PIT treatment, and TUNEL staining images showed the occurrence of cell apoptosis, which was also testified by HE staining. This research provides MRP1 as a novel target for PIT and presents a prospective way for treating drug resistant SCLC and, thus, should be further studied.

Combining transcatheter arterial embolization with iodized oil containing Apatinib inhibits HCC growth and metastasis.

Transcatheter arterial embolization (TAE) plays an important role in clinical liver tumor therapy. However, hypoxia after TAE limit the medium-long term efficacy of TAE. Thus, in our study, we explored the treatment effect and mechanism of combining transcatheter arterial embolization with adopted iodized oil containing Apatinib on suppressing tumor growth and metastasis. We simulated the changing of tumor microenvironment before and after TAE both in vitro and in vivo models. The anti-angiogenic effect of Apatinib was explored by bioassays in human umbilical vein endothelial cells (HUVECs), including cell migration, invasion and apoptosis, tube formation, and wound healing. Further experiments showed that Apatinib inhibited tumor microangiogenesis to achieve the aims of inhibiting tumor growth and recurrence by means of down-regulating the phosphorylation of the RAF-mek-erk, PI3K-akt and P38MAPK pathways. The antitumor growth and anti-angiogenic effect of Apatinib was further validated by the animal experiment. Taken together, we concluded that Apatinib inhibits the angiogenesis and growth of liver cancer by down-regulating the PI3K-akt, RAF-mek-erk and P38MAPK pathways, and has a stronger inhibitory effect in hypoxic environments. Combining TAE with adopted iodized oil containing Apatinib has a stronger inhibitory effect in VX2 liver tumor growth and metastasis, which suggesting such combinations may provide a new target and strategy for interventional therapy of liver cancer.

Effects of keto acid supplements on Chinese patients receiving maintenance hemodialysis: a prospective, randomized, controlled, single-center clinical study.

BACKGROUND: The effects of keto acid (KA) supplements on Chinese patients receiving maintenance hemodialysis (MHD) are unclear. This study aimed to evaluate the effects of KA supplementation on nutritional status, inflammatory markers, and bioelectric impedance analysis (BIA) parameters in a cohort of Chinese patients with MHD without malnutrition. METHODS: This was a prospective, randomized, controlled, single-center clinical study conducted in 2011 till 2014. Twenty-nine patients with MHD were randomly assigned to a control (n = 14) or a KA (n = 15) group. The control group maintained a dietary protein intake of 0.9 g/kg/day. The KA group received additional KA supplement (0.1 g/kg/day). BIA was used to determine the lean tissue mass, adipose tissue mass, and body cell mass. The patients' nutritional status, dialysis adequacy, and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test. RESULTS: The daily total energy intake for both groups was about 28 kcal/kg/day. After 6 months, the Kt/V (where K is the dialyzer clearance of urea, t is the dialysis time, and V is the volume of the distribution of urea) was 1.33 ±â€Š0.25 in KA group, and 1.34 ±â€Š0.25 in the control group. The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group. In addition, the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group. There were no significant differences between the groups with respect to the anthropometry parameters, dialysis adequacy, serum calcium and phosphorus levels, inflammatory markers, and amino-acid profiles, or in relation to the parameters determined by BIA. Both groups achieved dialysis adequacy and maintained nutritional status during the study. CONCLUSIONS: In this cohort of Chinese patients with MHD, the patients in the control group whose dietary protein intake was 0.9 g/kg/day and total energy intake was 28 kcal/kg/day, maintained well nutritional status during study period. The KA supplement (0.1 g/kg/day) did not improve the essential amino acid/non-essential amino acid ratio, nor did it change the patients' mineral metabolism, inflammatory parameters, or body compositions.

Effects of keto acid supplements on Chinese patients receiving maintenance hemodialysis: a prospective, randomized, controlled, single-center clinical study / 中华医学杂志(英文版)

BACKGROUND@#The effects of keto acid (KA) supplements on Chinese patients receiving maintenance hemodialysis (MHD) are unclear. This study aimed to evaluate the effects of KA supplementation on nutritional status, inflammatory markers, and bioelectric impedance analysis (BIA) parameters in a cohort of Chinese patients with MHD without malnutrition.@*METHODS@#This was a prospective, randomized, controlled, single-center clinical study conducted in 2011 till 2014. Twenty-nine patients with MHD were randomly assigned to a control (n = 14) or a KA (n = 15) group. The control group maintained a dietary protein intake of 0.9 g/kg/day. The KA group received additional KA supplement (0.1 g/kg/day). BIA was used to determine the lean tissue mass, adipose tissue mass, and body cell mass. The patients' nutritional status, dialysis adequacy, and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test.@*RESULTS@#The daily total energy intake for both groups was about 28 kcal/kg/day. After 6 months, the Kt/V (where K is the dialyzer clearance of urea, t is the dialysis time, and V is the volume of the distribution of urea) was 1.33 ± 0.25 in KA group, and 1.34 ± 0.25 in the control group. The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group. In addition, the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group. There were no significant differences between the groups with respect to the anthropometry parameters, dialysis adequacy, serum calcium and phosphorus levels, inflammatory markers, and amino-acid profiles, or in relation to the parameters determined by BIA. Both groups achieved dialysis adequacy and maintained nutritional status during the study.@*CONCLUSIONS@#In this cohort of Chinese patients with MHD, the patients in the control group whose dietary protein intake was 0.9 g/kg/day and total energy intake was 28 kcal/kg/day, maintained well nutritional status during study period. The KA supplement (0.1 g/kg/day) did not improve the essential amino acid/non-essential amino acid ratio, nor did it change the patients' mineral metabolism, inflammatory parameters, or body compositions.

In vitro and in vivo assessment of the proresolutive and antiresorptive actions of resolvin D1: relevance to arthritis.

BACKGROUND: Resolvin D1 (RvD1), an important member of resolvins, exerts a wide spectrum of biological effects, including resolution of inflammation, tissue repair, and preservation of cell viability. The aim of the present study is to investigate the anti-arthritic potential and clarify the bone protective actions of RvD1 in vitro and in vivo. METHODS: RAW264.7 cells were treated with 50 ng/ml LPS for 72 h in the presence or absence of RvD1 (0-500 nM). Primary human monocytes were treated with M-CSF + RANKL for 14 days ± RvD1 (0-500 nM) with or without siRNA against RvD1 receptor FPR2. Expressions of inflammatory mediators, degrading enzymes, osteoclasts (OC) formation, and bone resorption were analyzed. The therapeutic effect of RvD1 (0-1000 ng) was carried out in murine collagen antibody-induced arthritis. Arthritis scoring, joint histology, and inflammatory and bone turnover markers were measured. RESULTS: RvD1 is not toxic and inhibits OC differentiation and activation. It decreases bone resorption, as assessed by the inhibition of TRAP and cathepsin K expression, hydroxyapatite matrix resorption, and bone loss. In addition, RvD1 reduces TNF-α, IL-1ß, IFN-γ, PGE2, and RANK and concurrently enhances IL-10 in OC. Moreover, in arthritic mice, RvD1 alleviates clinical score, paw inflammation, and bone and joint destructions. Besides, RvD1 reduces inflammatory mediators and markedly decreases serum markers of bone and cartilage turnover. CONCLUSION: Our results provide additional evidence that RvD1 plays a key role in preventing bone resorption and other pathophysiological changes associated with arthritis. The study highlights the clinical relevance of RvD1 as a potential compound for the treatment of inflammatory arthritis and related bone disorders.