Ginsenoside Rg1 Induces Autophagy in Colorectal Cancer through Inhibition of the Akt/mTOR/p70S6K Pathway.

This study aimed to elucidate the anti-colon cancer mechanism of ginsenoside Rg1 in vitro and in vivo. Cell viability rate was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tetrazolium assay. The inhibitory effect of ginsenoside Rg1 against CT26 cell proliferation gradually increased with increasing concentration. The in vivo experiments also demonstrated an antitumor effect. The monodansylcadaverine (MDC), transmission electron microscopy (TEM), and expression of autophagy marker proteins confirmed that ginsenoside Rg1 induced autophagy in vitro. Ginsenoside Rg1 induced autophagy death of CT26 cells, but this effect could be diminished by autophagy inhibitor (3-methyladenine, 3-MA). Additionally, in a xenograft model, immunohistochemical analysis of tumor tissues showed that the LC3 and Beclin-1 proteins were highly expressed in the tumors from the ginsenoside Rg1-treated nude mice, confirming that ginsenoside Rg1 also induced autophagy in vivo. Furthermoer, both in vivo and in vitro, the protein expressions of p-Akt, p-mTOR, and p-p70S6K were inhibited by ginsenoside Rg1, which was verified by Akt inhibitors. These results indicated that the mechanism of ginsenoside Rg1 against colon cancer was associated with autophagy through inhibition of the Akt/mTOR/p70S6K signaling pathway.

Efficacy and Safety of Huangqi Guizhi Wuwu Decoction for Oxaliplatin-Induced Peripheral Neurotoxicity: A Systematic Review and Meta-Analysis.

Objective: Oxaliplatin is a first-line chemotherapy drug for the treatment of colorectal cancer, but its induced oxaliplatin-induced peripheral neurotoxicity (OIPN) affect the chemotherapy process and quality of life of tumor patients. OIPN is a serious and potentially permanent side effect of cancer treatment. Currently, no unified standard has been established for preventing and treating OIPN in Western medicine. Therefore, it is very important to seek effective prevention and treatment measures. Many clinical trials have reported that Huangqi Guizhi Wuwu decoction can effectively prevent OIPN, but substantial evidence base to support this treatment is lacking. We collected existing literature and evaluated the clinical efficacy and safety of Huangqi Guizhi Wuwu decoction for OIPN by performing a meta-analysis. Methods: We systematically searched China National Knowledge Internet (CNKI), VIP, Wan Fang Database, Pubmed, EMBASE, and Cochrane Library from inception through to Oct 2022 to identify only randomized controlled trials examining the prevention of OIPN using Huangqi Guizhi Wuwu decoction. This search was supplemented by manual retrieval, including dissertations and conference papers. All data were analyzed using RevMan 5.3 software. Results: A total of 18 papers involving 564 patients in the treatment group and 523 patients in the control group were included. A total of 17 articles reported the overall incidence of peripheral neurotoxicity (I² = 0%), and the overall incidence of peripheral neurotoxicity in the treatment group was 0.27 times higher than in the control group (95% CI: 0.20-0.36). A total of 16 articles reported the incidence of level III-IV severe peripheral neurotoxicity (I² = 0%), which was 0.16 times higher in the treatment group than in the control group (95% CI: 0.09-0.32). In the Huangqi Guizhi Wuwu VS no-interference subgroup, it showed that the incidence of severe peripheral neurotoxicity in the treat group was significantly lower than in the control group (OR:0.13, 95% CI:0.06-0.28). But in the Huangqi Guizhi Wuwu VS west medicine therapy subgroup, no significant difference between Huangqi Quizhi Wuwu and conventional Western medicine was observed for the prevention and treatment of severe OIPN (OR:0.37, 95% CI:0.09-1.53). A total of 2 articles were reported median nerve conduction velocity (I² = 51.2%); and no significant difference was found between the treatment and control groups (SMD: 1.43; 95% CI: 0.80-2.08); 4 studies showed Huangqi Guizhi Wuwu decoction did not increase the incidence of chemotherapy-related adverse reactions and was safe. Conclusions: Our current findings support the application of Huangqi Guizhi Wuwu decoction for the clinical prevention and treatment of patients with OIPN. However, high-quality RCT research is still needed to further exploration. The potential impact of Huangqi Guizhi Wuwu decoction on the quality of life or treatment compliance of cancer patients needs further research.

Tanshinone IIA Alleviates the Biological Characteristics of Colorectal Cancer via Activating the ROS/JNK Signaling Pathway.

BACKGROUND: Tanshinone IIA (Tan IIA) exerts a significant inhibitory effect on various tumor cells since it induces cell apoptosis and affects the proliferation, differentiation, metastasis, and invasion of tumor cells. However, the mechanism underlying the antitumor activity of Tan IIA has not been totally elucidated. OBJECTIVE: This study aimed to uncover the role of Tan IIA in colorectal cancer (CRC) and its potential mechanism of action. METHODS: Cell proliferation was assessed using CCK-8 and colony formation assays. Western blot analysis was carried out to detect the expression of related proteins. Cell apoptosis was assessed using flow cytometry. Furthermore, tumor size and tumor weight of CRC xenograft mice were recorded before and after Tan IIA treatment. The production of reactive oxygen species (ROS) was measured by a ROS kit. RESULTS: The results revealed that Tan IIA induced autophagy and apoptosis via activating the ROS/JNK signaling pathway in CRC cells, thus inhibiting the progression of CRC in vivo. CONCLUSION: The aforementioned findings indicated that Tan IIA exerted an antiproliferative effect on CRC by inducing cell autophagy and apoptosis via activating the ROS/JNK signaling pathway. Therefore, Tan IIA may be considered a potential therapeutic agent for treating CRC.

Data mining analysis reveals key acupoints and meridians for the treatment of chemotherapy-induced peripheral neuropathy.

OBJECTIVE: To explore effective acupoints and combinations for the treatment of chemotherapy-induced peripheral neuropathy (CIPN) METHODS: Clinical controlled trials and randomized controlled trials of acupuncture for CIPN were sourced from PubMed, Embase, Web of Science, and Chinese databases, including the Wanfang database, VIP Journals database, and China National Knowledge Infrastructure database. The quality of eligible research was evaluated based on CONSORT and STRICTA statements. The common acupoints, meridians, and acupoint combinations were determined from acupuncture prescriptions reporting positive effects and were analyzed using SPSS 23.0 and SPSS Modeler 14.1. Finally, a complex network was constructed using Cytoscape 3.8.2 to explore the core acupoints. RESULTS: The quality of 24 clinical trials was evaluated, and 20 acupuncture prescriptions that reported positive outcomes were included in subsequent data mining analysis. The most frequently used acupoints are ST36, LI11, LI4, LR3, and SP6. Meanwhile, they are also the core acupoints in acupuncture prescriptions according to the complex network with 28 nodes and 177 edges. The most commonly used meridians were the large intestine, stomach, and spleen. Acupoint combinations of LI11 and ST36, SP6 and ST36 were frequently used. CONCLUSION: Our study provides a reference for the selection of effective acupoints for CIPN treatment and a basis for the effective use of this form of traditional Chinese medicine. Furthermore, we found limitations in the design and implementation of the available clinical research, which should be minimized in future studies.

Ginsenoside Rg3 nanoparticles with permeation enhancing based chitosan derivatives were encapsulated with doxorubicin by thermosensitive hydrogel and anti-cancer evaluation of peritumoral hydrogel injection combined with PD-L1 antibody.

BACKGROUND: Combination of chemotherapy and immune checkpoint inhibitor therapy has greatly improved the anticancer effect on multiple malignancies. However, the efficiency on triple-negative breast cancer (TNBC) is limited, since most patients bear "cold" tumors with low tumor immunogenicity. Doxorubicin (DOX), one of the most effective chemotherapy agents, can induce immunogenic cell death (ICD) and thus initiating immune response. METHODS: In this study, to maximize the ICD effect induced by DOX, chitosan and cell-penetrating peptide (R6F3)-modified nanoparticles (PNPs) loaded with ginsenoside Rg3 (Rg3) were fabricated using the self-assembly technique, followed by co-encapsulation with DOX based on thermo-sensitive hydrogel. Orthotopic tumor model and contralateral tumor model were established to observe the antitumor efficacy of the thermo-sensitive hydrogel combined with anti-PD-L1 immunotherapy, besides, the biocompatibility was also evaluated by histopathological. RESULTS: Rg3-PNPs strengthened the immunogenic cell death (ICD) effect induced by DOX. Moreover, the hydrogel co-loading Rg3-PNPs and DOX provoked stronger immune response in originally nonimmunogenic 4T1 tumors than DOX monotherapy. Following combination with PD-L1 blocking, substantial antitumor effect was achieved due to the recruitment of memory T cells and the decline of adaptive PD-L1 enrichment. CONCLUSION: The hydrogel encapsulating DOX and highly permeable Rg3-PNPs provided an efficient strategy for remodeling immunosuppressive tumor microenvironment and converting immune "cold" 4T1 into "hot" tumors.

A risk scoring system to predict the individual incidence of early-onset colorectal cancer.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is increasing at an alarming rate and further studies are needed to identify risk factors and to develop prevention strategies. METHODS: Risk factors significantly associated with EOCRC were identified using meta-analysis. An individual risk appraisal model was constructed using the Rothman-Keller model. Next, a group of random data sets was generated using the binomial distribution function method, to determine nodes of risk assessment levels and to identify low, medium, and high risk populations. RESULTS: A total of 32,843 EOCRC patients were identified in this study, and nine significant risk factors were identified using meta-analysis, including male sex, Caucasian ethnicity, sedentary lifestyle, inflammatory bowel disease, and high intake of red meat and processed meat. After simulating the risk assessment data of 10,000 subjects, scores of 0 to 0.0018, 0.0018 to 0.0036, and 0.0036 or more were respectively considered as low-, moderate-, and high-risk populations for the EOCRC population based on risk trends from the Rothman-Keller model. CONCLUSION: This model can be used for screening of young adults to predict high risk of EOCRC and will contribute to the primary prevention strategies and the reduction of risk of developing EOCRC.

A Prognostic Model Based on the Immune-Related lncRNAs in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors with a poor prognosis. At present, the pathogenesis is not completely clear. Therefore, finding reliable prognostic indicators for CRC is of important clinical significance. In this study, bioinformatics methods were used to screen the prognostic immune-related lncRNAs of CRC, and a prognostic risk scoring model based on immune-related lncRNAs signatures were constructed to provide a basis for prognostic evaluation and immunotherapy of CRC patients. METHODS: The clinical information and RNA-seq data of CRC patients were obtained from The Cancer Genome Atlas (TCGA) database. The information of immune-related lncRNA was downloaded from the immunology database and analysis portal. The differentially expressed immune-related lncRNAs (IRLs) were screened by the edgeR package of R software. The prognostic value of IRLs was studied. Based on Cox regression analysis, a prognostic index (IRLPI) based on IRLs was established, and the relationship between the risk score and the clinicopathological characteristics of CRC was analyzed to determine the effectiveness of the risk score model as an independent prognostic factor. RESULTS: A total of 240 differentially expressed IRLs were identified between normal colorectal cancer tissues and normal colorectal cancer tissues, in which 8 were significantly associated with the survival of CRC patients (P < 0.05), including LINC00461, LINC01055, ELFN1-AS1, LMO7-AS1, CYP4A22-AS1, AC079612.1, LINC01351, and MIR31HG. And most of the lncRNAs related to survival were risk factors for the prognosis of CRC. The index established based on the 7 survival-related IRLs found to be highly accurate in monitoring CRC prognosis. Besides, IRLPI was significantly correlated with a variety of pathological factors and immune cell infiltration. CONCLUSION: Eight immune-related lncRNAs closely related to the prognosis of CRC patients were identified from the TCGA database. At the same time, an independent IRLPI was constructed, which may be helpful for clinicians to assess the prognosis of patients with CRC and to formulate individualized treatment plans.

Human gut-microbiome interplay: Analysis of clinical studies for the emerging roles of diagnostic microbiology in inflammation, oncogenesis and cancer management.

Microorganisms have been known to coexist in various parts of human body including the gut. The interactions between microbes and the surrounding tissues of the host are critical for fine fettle of the gut. The incidence of such microorganisms tends to vary among specific type of cancer affected individuals. Such microbial communities of specific tumor sites in cancer affected individuals could plausibly be used as prognostic and/or diagnostic markers for tumors associated with that specific site. Microorganisms of intestinal and non-intestinal origins including Helicobacter pylori can target several organs, act as carcinogens and promote cancer. It is interesting to note that diets causing inflammation can also increase the cancer risk. Yet, dietary supplementation with prebiotics and probiotics can reduce the incidence of cancer. Therefore, both diet and microbial community of the gut have dual roles of prevention and oncogenesis. Hence, this review intends to summarize certain important details related to gut microbiome and cancer.

Catheter allotopia with totally implantable access port: A report of three cases and literature review.

Early detection and treatment are critical for preventing catheter allotopia in the totally implantable access ports and whenever possible, the right internal jugular vein should be selected as the first puncture point.

Platinum accumulation in oxaliplatin-induced peripheral neuropathy.

Oxaliplatin-induced peripheral neuropathy (OIPN) is a common and dose-limiting toxic effect that markedly limits the use of oxaliplatin and affects the quality of life. Although it is common, the underlying mechanisms of OIPN remain ambiguous. Recent studies have shown that the platinum accumulation in peripheral nervous system, especially in dorsal root ganglion, is a significant mechanism of OIPN. Several specific transporters, including organic cation transporters, high-affinity copper uptake protein1 (CTR1), ATPase copper transporting alpha (ATP7A) and multidrug and toxin extrusion protein 1 (MATE1), could be associated with this mechanism. This review summarizes the current research progress about the relationship between platinum accumulation and OIPN, as well as suggests trend for the future research.

Olfactory Dysfunction in Patients With Coronavirus Disease 2019: A Review.

The coronavirus disease 2019 (COVID-19) pandemic is wreaking havoc on public-health and economic systems worldwide. Among the several neurological symptoms of patients with COVID-19 reported in clinical practice, olfactory dysfunction (OD) is the most common. OD occurs as the earliest or the only clinical manifestation in some patients. Increasing research attention has focused on OD, which is listed as one of the main diagnostic symptoms of severe acute respiratory syndrome-coronavirus-2 infection. Multiple clinical and basic-science studies on COVID-19-induced OD are underway to clarify the underlying mechanism of action. In this review, we summarize the clinical characteristics, mechanisms, evaluation methods, prognosis, and treatment options of COVID-19-induced OD. In this way, we hope to improve the understanding of COVID-19-induced OD to aid early identification and precise intervention.

Bibliometric Analysis Reveals a 20-Year Research Trend for Chemotherapy-Induced Peripheral Neuropathy.

OBJECTIVE: A lot of research has focused on the field of chemotherapy-induced peripheral neuropathy (CIPN). In this study, we performed a bibliometric analysis of CIPN-related publications to identify the key research areas and trends over the last 20 years. METHODS: We searched the Web of Science core collection for publications related to CIPN that were published between January 2001 and September 2021. We then performed bibliometric analysis and visualization using Microsoft Excel 2019, VOSviewer, and the Bibliometric online analysis platform (https://bibliometric.com/). RESULTS: In total, we identified 2,188 eligible publications in the field of CIPN, with an increasing trend in the annual number of publications. The United States and Italy were dominant in the CIPN field. Supportive Care in Cancer was the most productive journal. G. Cavaletti and A.A. Argyriou published the largest number of papers. Of all institutions, the University of Milano-Bicocca, Italy, published the highest number of papers. Analysis of the co-occurrence of keywords revealed the specific characteristics relating to the four main clusters: oxaliplatin, paclitaxel, pain management, and quality of life (QOL). Newly emerging research focusses predominantly on neuroinflammatory mechanisms and non-pharmacological interventions for CIPN. CONCLUSION: This bibliometric study reviewed the evolutionary trends in CIPN research and identified current research hotspots and research trends. In addition, we identified journals, institutions, and authors, with the highest levels of impact to enhance the collaboration and learning.

Balanophorin B inhibited glycolysis with the involvement of HIF-1α.

AIMS: Cancer cells exhibit a metabolic change called aerobic glycolysis compared with normal cells. Balanophorin B is a terpenoid ingredient reported from the genus Balanophora. In this research, we studied the effect of balanophorin B on glycolysis of HepG2 cells and Huh-7 cells under hypoxia. MAIN METHODS: The Warburg effect was monitored by assessing glucose uptake, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Key enzymes in the glycolytic pathway and HIF-1α protein expression and degradation were analyzed by real-time PCR and western blotting. The anti-cancer effect of balanophorin B in vivo was also investigated. KEY FINDINGS: Balanophorin B inhibited the proliferation, glucose uptake, and ECAR in both HepG2 cells and Huh-7 cells. In addition, balanophorin B inhibited the protein level of HIF-1α and its downstream targets LDHA and HKII under hypoxia, whereas HIF-1α mRNA level did not change after balanophorin B treatment. The HIF-1α plasmid reversed the inhibition of balanophorin B on glycolysis, and the proteasome inhibitor MG132 attenuated the effect of balanophorin B on HIF-1α protein expression, suggesting that balanophorin B might post-transcriptionally affect HIF-1α. Moreover, balanophorin B increased the expression of VHL and PHD2. HIF-1α siRNA also greatly attenuated the inhibitory effect of balanophorin B on HepG2 cells glucose uptake. Balanophorin B significantly inhibited tumor growth in vivo, without causing obvious toxicity to mice. SIGNIFICANCE: These data suggest that balanophorin B inhibits glycolysis probably via an HIF-1α-dependent pathway, and the ubiquitin-proteasome pathway was greatly involved in the induction of balanophorin B on HIF-1α degradation.

Exploring the Possible Mechanism and Drug Targets of Huang-Qi-Gui-Zhi-Wu-Wu Decoction for the Treatment of Chemotherapy-Induced Peripheral Neuropathy on Network Pharmacology.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment, which may influence its successful completion. The Huang-Qi-Gui-Zhi-Wu-Wu decoction (HQGZWWD) has been widely used to treat CIPN in China although the pharmacological mechanisms involved have not been clarified. Using the network pharmacology approach, this study investigated the potential pathogenesis of CIPN and the therapeutic mechanisms exerted by the HQGZWWD herbal formula in CIPN. The targets of HQGZWWD were identified using traditional Chinese medicine (TCM) databases (TCMSP and ETCM) and prediction platforms (PharmMapper and TargetNet), and the genes of CIPN were collected by DisGeNET, GeneCards, and literature search. The common target interaction network between herbal formula and diseases was constructed by using Cytoscape. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal the mechanism and efficacy of HQGZWWD in the treatment of CIPN. A total of 153 CIPN-related genes were screened, and a protein-protein interaction (PPI) network with 96 nodes and 424 edges was constructed. Sixty-three active components were retrieved from HQGZWWD, with a herb-composite compound-target network including 748 nodes and 5448 edges. Forty-one targets belong to the above two networks. The analysis of network results and literature review shows that the main pathological processes of CIPN may be the inflammatory response and nerve injury, and HQGZWWD plays a therapeutic role in CIPN by regulating inflammatory response and repairing nerve injury, thus verifying the reliable efficacy of this herbal formula. In addition, we found two new potential therapeutic targets (CDK7 and GSTM2) warranting further investigation. This study fully illustrates that TCM has the characteristics of a multicompound, multitarget, and multipathway treatment, which is of great significance to study the curative effect of herbal formulations.

Curcumol improves cisplatin sensitivity of human gastric cancer cells through inhibiting PI3K/AKT pathway.

BACKGROUND: Curcumol was presented to unleash antitumor effects in a variety of cancers, including gastric cancer. However, the relevance between curcumol and cisplatin resistance in gastric cancer still remains unclear. Therefore, the current research was performed to survey the role of curcumol in cisplatin sensitivity in gastric cancer. METHODS: First, BGC-823 and BGC-823/DDP cells were incubated with cisplatin for 48 hr and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) analysis was applied to determine the inhibition rate of cell proliferation and the half-maximal inhibitory concentration (IC50 ) of cisplatin. In addition, BGC-823 and BGC-823/DDP cells were treated with curcumol for 48 hr followed with detection of cell viability and apoptosis using MTT and flow cytometry assay, respectively. Moreover, MTT analysis was applied to test the effects of curcumol on cisplatin sensitivity in gastric cancer cells. Lastly, Western blot assay and qRT-PCR analysis were utilized to check the functions of curcumol on PI3K/AKT pathway-related markers. RESULTS: We found that BGC-823/DDP cells exhibited stronger resistance to cisplatin compared with BGC-823 cells. Furthermore, curcumol evidently reduced cell proliferation and facilitated cell apoptosis in BGC-823/DDP and BGC-823 cells. Moreover, results from MTT assay demonstrated that curcumol notably promoted the suppression effect of cisplatin and decreased the IC50 of cisplatin in BGC-823/DDP and BGC-823 cells. It was also presented that curcumol suppressed the PI3K/AKT pathway dose-dependently in BGC-823/DDP and BGC-823 cells. CONCLUSION: The findings in the current research demonstrated that curcumol could promote the sensitivity of gastric cancer cells to cisplatin-based chemotherapies via inhibiting the phosphatidylinositol 3-kinase (PI3K)/Protein Kinase B (AKT) pathway.

Tanshinone IIA induces autophagy in colon cancer cells through MEK/ERK/mTOR pathway.

BACKGROUND: Colon cancer is a common malignancy of the digestive tract. The search for effective drugs to treat colon cancer has become the focus of current researches. Tanshinone IIA (Tan IIA) is a fat-soluble component extracted from tanshinone, a traditional Chinese medicine. Tan IIA can modulate the occurrence and development of tumors, but its effect on autophagy in colon cancer cells has not been reported. METHODS: Two types of colon cancer cell lines were selected and different concentrations of Tan IIA were used to treat cells at different time points. Cell Counting Kit-8 assay (CCK-8) was used to detect the effect of Tan IIA on cell proliferation; transmission electron microscopy was used to observe the formation of autophagosomes; reverse transcription-polymerase chain reaction (RT-qPCR) and western blot were used to detect the expression of autophagy related genes and proteins. Cell transfection was used to interfere with MEK (mitogen-activated extracellular signal-regulated kinase) expression, and RT-qPCR and western blot were used to detect the expression of MEK/ERK/mTOR pathway-related proteins. RESULTS: Tan IIA resulted in a significant reduction in the viability of the two kinds of colon cancer cells. The number of autophagosomes increased significantly after the treatment of Tan IIA into these cells. Addition of autophagy inhibitor 3-MA (3-Methyladenine) improved the increase of autophagosomes in cells induced by Tan IIA. At the same time, Tan IIA induced the expression of autophagy-related proteins in the two colon cancer cell lines. When Tan IIA induced autophagy in colon cancer cells, the expression of MEK/ERK/mTOR pathway-related proteins increased significantly. After interfering with the expression of MEK, the expression of autophagy decreased significantly, indicating that Tan IIA promoted autophagy of colon cancer cells through MEK/ERK/mTOR pathway. CONCLUSIONS: Tan IIA stimulates autophagy in colon cancer cells through MEK/ERK/mTOR pathway, hence inhibiting the growth of colon cancer cells.

Bronchopleural fistula in squamous cell lung cancer following anlotinib treatment: A case report.

Anlotinib is a multi-target tyrosine kinase inhibitor and has been approved for the treatment of patients with advanced non-small cell lung cancer. The most common adverse events of this treatment include hypertension, fatigue, thyroid-stimulating hormone elevation, hypertriglyceridemia, hand-foot syndrome and hypercholesterolemia. The present study reported the case of a 69-year-old man with squamous cell lung cancer that experienced disease progression following first-line and second-line chemotherapy. Subsequently, anlotinib was administered as a third-line therapy. Following the second cycle of oral targeted therapy, the patient was admitted to the hospital with a one-week history of chest tightnesss, shortness of breath and cough blood-stained sputum and necrosis. Computed tomography scan showed: Bronchopleural fistula (BPF) complicating lung cancer. However, symptoms were not relieved following anti-infective treatment and the patient subsequently died of respiratory failure. To the best of our knowledge, this is the first case of bronchopleural fistula associated with the use of anlotinib in a patient with squamous cell lung cancer.

Self-assembled naphthalimide derivatives as an efficient and low-cost electron extraction layer for n-i-p perovskite solar cells.

Based on self-assembly, novel electron extraction layers (EELs) composed of naphthalimide (NPI) derivatives are constructed for application in n-i-p perovskite solar cells. Upon molecular energy level modulation, the power conversion efficiencies have been largely improved from 5.4% to 16%. Such low-cost and highly regulable EELs are promising for future commercial applications.

FuFangChangTai Decoction Activates Macrophages via Inducing Autophagy.

The traditional Chinese medicine decoction FuFangChangTai (FFCT) has been used in the therapy of colon cancer clinically, yielding alleviated toxicity and enhanced immunity. In our previous study, FFCT exerted its antitumor activity not only by inducing apoptosis but also by activating autophagy to eliminate tumor cells. However, its mechanism is not well understood. The purpose of this study was to investigate the relationship between macrophages activation and FFCT-induced autophagy. Results showed that FFCT could induce autophagy in colon cancer, as demonstrated by increased level of intracellular autophagy marker LC3 II in CT26.WT cells by fluorescence microscope and western blot assay. FFCT also facilitated numbers of vesicular bodies with bilayer membrane in CT26.WT cells, which were indicative of autophagosomes formation. Autophagosomes secreted by FFCT-treated CT26.WT cells can activate M1 type macrophages, accompanied with increased expression of costimulatory molecules CD86 and CD40 on the surface of RAW264.7 cells, and more inflammatory cytokines secretion, such as TNF-α, IL-6, MCP-1, and IL-1ß. mRNA expressions of M2 macrophages markers, such as IL-10, CD206, Arg-1, and FIZZ-1, were downregulated. And this process helps regulate the polarization of macrophages and promote the immune response. These findings support a mechanism of FFCT-induced autophagy and provide novel evidence demonstrating that macrophages are involved in FFCT-induced autophagy progression.

Reversal effect of ginsenoside Rh2 on oxaliplatin-resistant colon cancer cells and its mechanism.

Chemotherapy is an important treatment modality for colon cancer, however, drug resistance is the main factor leading to treatment failure. Ginsenoside Rh2 (G-Rh2), the main bioactive metabolite of ginseng, is known to possess the ability to potently induce cell apoptosis, inhibit cell proliferation and reverse multidrug resistance in a variety of cancer cells. The present study examined the effect of G-Rh2 on oxaliplatin (L-OHP)-resistant colon cancer cells and its potential mechanism. L-OHP-resistant colon cancer cells (LoVo/L-OHP) and LoVo cells were used in the present study. The effect of G-Rh2 on LoVo/L-OHP and LoVo cell proliferation was measured using a 3-(4,5 dimethylthiazol-z-yl)-3,5-diphenyltetrazolium bromide assay. The effects of G-Rh2 on LoVo/L-OHP and LoVo cell apoptosis were detected by flow cytometry. The mRNA and protein expression of apoptosis-related genes Bax, Bcl-2 and caspase-3, drug resistance-related genes P-glycoprotein (P-gp) and Smad4, were determined in LoVo/L-OHP and LoVo cells treated with G-Rh2 by reverse transcription-quantitative polymerase chain reaction and western blot analyses. G-Rh2 treatment significantly inhibited the proliferation and induced the apoptosis of LoVo/L-OHP and LoVo cells. In addition, G-Rh2 treatment resulted in a significant increase in pro-apoptotic factors, Bax and caspase-3, and decrease in anti-apoptotic factor Bcl-2 in the LoVo/L-OHP and LoVo cells. Furthermore, G-Rh2 treatment significantly decreased the levels of P-gp and increased the levels of Smad4 in the LoVo/L-OHP and LoVo cells. It was found that L-OHP had no significant effects on LoVo/L-OHP cell proliferation or apoptosis, whereas G-Rh2 + L-OHP treatment significantly inhibited LoVo/L-OHP cell proliferation and induced apoptosis. L-OHP had no significant effects on the expression of P-gp, Smad4, Bcl-2, Bax or caspase-3 in LoVo/L-OHP cells. Treatment with G-Rh2 + L-OHP significantly reduced the expression of P-gp and Bcl-2, and enhanced the expression levels of Smad4, Bax and caspase-3. These findings demonstrated that G-Rh2 reversed the drug resistance of LoVo/L-OHP cells to L-OHP, and this may be mediated by inhibiting cell proliferation and promoting apoptosis and regulating the expression of drug resistance genes. These results suggest that G-Rh2 may function as a potent anticancer drug for drug resistance in colon cancer treatment.