Ultrahigh Enzyme Loading Metal-Organic Frameworks for Deep Tissue Pancreatic Cancer Photoimmunotherapy.

Protein drugs hold promise in treating multiple complex diseases, including cancer. The priority of protein drug application is precise delivery of substantial bioactive protein into tumor site. Metal-organic-framework (MOF) is widely considered as a promising carrier to encapsulate protein drug owing to the noncovalent interaction between carrier and protein. However, limited loading efficiency and potential toxicity of metal ion in MOF restrict its application in clinical research. Herein, a tumor targeted collagenase-encapsulating MOF via protein-metal ion-organic ligand coordination (PMOCol ) for refining deep tissue pancreatic cancer photoimmunotherapy is developed. By an expedient method in which the ratio of metal ion, histidine residues of protein and ligand is precisely controlled, PMOCol is constructed with ultrahigh encapsulation efficiency (80.3 wt%) and can release collagenase with high enzymatic activity for tumor extracellular matrix (ECM) regulation after reaching tumor microenvironment (TME). Moreover, PMOcol exhibits intensively poorer toxicity than the zeolitic imidazolate framework-8 biomineralized protein. After treatment, the pancreatic tumor with abundant ECM shows enhanced immunocyte infiltration owing to extracellular matrix degradation that improves suppressive TME. By integrating hyperthermia agent with strong near-infrared absorption (1064 nm), PMOCol can induce acute immunogenicity to host immunity activation and systemic immune memory production to prevent tumor development and recurrence.

GARP-mediated active TGF-ß1 induces bone marrow NK cell dysfunction in AML patients with early relapse post-allo-HSCT.

Relapse is a leading cause of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML). However, the underlying mechanisms remain poorly understood. Natural killer (NK) cells play a crucial role in tumor surveillance and cancer immunotherapy, and NK cell dysfunction has been observed in various tumors. Here, we performed ex vivo experiments to systematically characterize the mechanisms underlying the dysfunction of bone marrow-derived NK (BMNK) cells isolated from AML patients experiencing early relapse after allo-HSCT. We demonstrated that higher levels of active transforming growth factor ß1 (TGF-ß1) were associated with impaired effector function of BMNK cells in these AML patients. TGF-ß1 activation was induced by the overexpression of glycoprotein A repetitions predominant on the surface of CD4+ T cells. Active TGF-ß1 significantly suppressed mTORC1 activity, mitochondrial oxidative phosphorylation, the proliferation, and cytotoxicity of BMNK cells. Furthermore, pretreatment with the clinical stage TGF-ß1 pathway inhibitor, galunisertib, significantly restored mTORC1 activity, mitochondrial homeostasis, and cytotoxicity. Importantly, the blockade of the TGF-ß1 signaling improved the antitumor activity of NK cells in a leukemia xenograft mouse model. Thus, our findings reveal a mechanism explaining BMNK cell dysfunction and suggest that targeted inhibition of TGF-ß1 signaling may represent a potential therapeutic intervention to improve outcomes in AML patients undergoing allo-HSCT or NK cell-based immunotherapy.

Unimolecular Cascaded Multienzyme Conjugates Modulate the Microenvironment of Diabetic Wound to Promote Healing.

An abnormal microenvironment underlies poor healing in chronic diabetic chronic wounds. However, effectively modulating the microenvironment of the diabetic wound remains a great challenge due to sustained oxidative stress and chronic inflammation. Here, we present a unimolecular enzyme-polymer conjugate that demonstrates excellent multienzymatic cascade activities. The cascaded enzyme conjugates (CECs) were synthesized by grafting poly(N-acryloyl-lysine) (pLAAm) from the glycan moieties of glucose oxidase (GOx) via glycan-initiated polymerization. The resulting CECs exhibited multiple enzymatic properties of GOx, superoxide dismutase mimic, and catalase mimic activities simultaneously. The CECs facilitated the depletion of high blood glucose, ROS scavenging, bacteria-killing, anti-inflammatory effects, and sustained oxygen generation, which restored the microenvironment in diabetic wounds. In vivo results from a diabetic mouse model confirmed the capacity and efficiency of the cascade reaction for diabetic wound healing. Our findings demonstrate that the three-in-one enzyme-polymer conjugates alone can modulate the diabetic microenvironment for wound healing.

Glutamine attenuates bisphenol A-induced intestinal inflammation by regulating gut microbiota and TLR4-p38/MAPK-NF-κB pathway in piglets.

Bisphenol A (BPA), as a kind of widely exerted environmental hazardous material, brings toxicity to both humans and animals. This study aimed to investigate the role of glutamine (Gln) in intestinal inflammation and microbiota in BPA-challenged piglets. Thirty-two piglets were randomly divided into four groups according to 2 factors including BPA (0 vs. 0.1%) and Gln (0 vs. 1%) supplemented in basal diet for a 42-day feeding experiment. The results showed BPA exposure impaired piglet growth, induced intestinal inflammation and disturbed microbiota balance. However, dietary Gln supplementation improved the growth performance, while decreasing serum pro-inflammatory cytokine levels in BPA-challenged piglets. In addition, Gln attenuated intestinal mucosal damage and inflammation by normalizing the activation of toll-like receptor 4 (TLR4)-p38/MAPK-nuclear factor-kappa B (NF-κB) pathway caused by BPA. Moreover, dietary Gln supplementation decreased the abundance of Actinobacteriota and Proteobacteria, and attenuated the decreased abundance of Roseburia, Prevotella, Romboutsia and Phascolarctobacterium and the content of short-chain fatty acids in cecum contents caused by BPA exposure. Moreover, there exerted potential relevance between the gut microbiota and pro-inflammatory cytokines and cecal short-chain fatty acids. In conclusion, Gln is critical nutrition for attenuating BPA-induced intestinal inflammation, which is partially mediated by regulating microbial balance and suppressing the TLR4/p38 MAPK/NF-κB signaling.

Treatment of immune thrombocytopenia with hetrombopag olamine tablets in a Kabuki syndrome patient with new KMT2D mutations.

Kabuki syndrome (KS) is a rare multisystem-affecting genetic disorder, and usually accompanied with autoimmune disorders such as immune thrombocytopenic purpura (ITP). Here, we report a 16-year-old patient with Kabuki syndrome with ITP and observe the therapeutic effect of TPO agonist hetrombopag olamine tablets. The duration of maintenance therapy and follow up were both 17 months. Whole exon sequencing (WES) of the patient's peripheral blood showed c.5775_5778del (p. Leu1926LysfsTer120) heterozygous mutation in the KMT2D gene, which was not reported before.

Acute liver injury induced by carbon tetrachloride reversal by Gandankang aqueous extracts through nuclear factor erythroid 2-related factor 2 signaling pathway.

The aims of this study were to evaluated the effect and underlying mechanism of Gandankang (GDK) aqueous extract in alleviating the acute liver injury induced by carbon tetrachloride (CCl4) in vivo and in vitro. Mice were divided into 5 groups (n = 8) for acute (Groups: control, 0.3 % CCl4, BD (Bifendate), 1.17, 2.34 and 4.68 mg/kg GDK) liver injury study. 10 µL/g CCl4 with corn oil were injected interperitoneally (i.p) expect the control group. HepG2 cells were used in vitro study. The results showed GDK can effectively inhibit liver damage and restore the structure and function of the liver. In mechanism, GDK inhibited CCl4-induced liver fibrosis and blocked the NF-κB pathway to effectively inhibit the hepatic inflammatory response; and inhibited CCl4-induced oxidative stress by upregulating the Keap1/Nrf2 pathway-related proteins and promoting the synthesis of several antioxidants. Additionally, it inhibited ferroptosis in the liver by regulating the expression of ACSl4 and GPX4. GDK reduced lipid peroxide generation in vitro by downregulating the production of reactive oxygen species and Fe2+ aggregation, thereby inhibiting ferroptosis and alleviating CCl4-induced hepatocyte injury. In conclusion, we describe the potential complex mechanism underlying the effect of GDK against acute liver injury.

Multimodal Sentiment Analysis Representations Learning via Contrastive Learning with Condense Attention Fusion.

Multimodal sentiment analysis has gained popularity as a research field for its ability to predict users' emotional tendencies more comprehensively. The data fusion module is a critical component of multimodal sentiment analysis, as it allows for integrating information from multiple modalities. However, it is challenging to combine modalities and remove redundant information effectively. In our research, we address these challenges by proposing a multimodal sentiment analysis model based on supervised contrastive learning, which leads to more effective data representation and richer multimodal features. Specifically, we introduce the MLFC module, which utilizes a convolutional neural network (CNN) and Transformer to solve the redundancy problem of each modal feature and reduce irrelevant information. Moreover, our model employs supervised contrastive learning to enhance its ability to learn standard sentiment features from data. We evaluate our model on three widely-used datasets, namely MVSA-single, MVSA-multiple, and HFM, demonstrating that our model outperforms the state-of-the-art model. Finally, we conduct ablation experiments to validate the efficacy of our proposed method.

[Overview of Status of Medical Device Registration and Quality Evaluation Requirements for Clinical Mass Spectrometry].

Mass spectrometry technology is becoming an important tool for clinical analysis due to its high specificity, high sensitivity and high multi-component detection capability. The current applications of this technology are mainly in liquid chromatography-tandem mass spectrometry (LC-MS/MS), matrix-assisted laser desorptionionization time-of-flight mass spectrometry (MALDI-TOF-MS), inductively coupled plasma mass spectrometry (ICP-MS), gas chromatography-mass spectrometry (GC-MS) and the related in vitro diagnostic kits. At present, the number of medical device (MD) based on mass spectrometry technology is growing rapidly, especially the number of LC-MS/MS and MALDI-TOF-MS registered MD products, and the standardization of relevant product quality requirements is also being effectively carried out. In general, clinical mass spectrometry equipment is still mainly imported, and the equipment price is relatively high. The development of mass spectrometry kits is mainly based on imported platforms, and domestic equipment is still in its infancy; the further promotion of clinical application of mass spectrometry also depends on the progress of the automation and standardization of the analysis procedure. To investigate the detection performance of mass spectrometry systems, it is necessary to fully consider the characteristics of mass spectrometry technology itself.

Postpartum Levothyroxine Adjustment and Its Impact Factors in Women With Hypothyroidism in Pregnancy.

OBJECTIVE: Women with hypothyroidism need to increase exogenous thyroid hormone levels during pregnancy to reduce adverse outcomes. Few studies have reported the effect of gestational levothyroxine (LT4) variations on postpartum LT4 treatment. METHODS: Women were classified as having subclinical hypothyroidism (SCH) (n = 101), overt hypothyroidism (OH) caused by autoimmune thyroiditis (AIT-OH), OH following thyroidectomy for benign thyroid disease (BA-OH) (n = 66), and OH after surgery for papillary thyroid cancer (PTC-OH) (n = 46). Thyroid function was monitored, and LT4 therapy was adjusted accordingly. RESULTS: After delivery, all women with SCH stopped LT4 treatment, and 57.4% of them restarted LT4 treatment in the following 1 year, independently of the gestational LT4 variations. Among patients with OH, after adjusted by gestational body weight, 49.1% of them had LT4 doses less than the prepregnancy dose (baseline) in late pregnancy, leading to LT4 reduction in postpartum. The LT4 dose was reduced to approximately 50% baseline for women with AIT-OH and BA-OH and reduced by 27% for women with PTC-OH. The reduction reasons for AIT-OH and BA-OH were thyroid-stimulating hormone levels of <2.5 mU/L during pregnancy and postpartum thyrotoxicosis occurrence (39.4%), and for PTC-OH, the reason was thyroid-stimulating hormone overinhibition (<1.0 mU/L) before delivery. CONCLUSION: For patients with SCH, postpartum LT4 treatment could initially be suspended. For women with OH, if the LT4 dose in late pregnancy was less than baseline, a prepregnancy dose reduced by 50%, 50%, and 27% should be applied after delivery for women with AIT-OH, BA-OH, and PTC-OH, respectively.

Mori fructus aqueous extracts attenuate carbon tetrachloride-induced renal injury via the Nrf2 pathway and intestinal flora.

Mori fructus aqueous extracts (MFAEs) have been used as a traditional Chinese medicine for thousands of years with the function of strengthening the liver and tonifying the kidney. However, its inner mechanism to alleviative renal injury is unclear. To investigate the attenuation of MFAEs on nephrotoxicity and uncover its potential molecular mechanism, we established a nephrotoxicity model induced by carbon tetrachloride (CCl4). The mice were randomly divided into control group, CCl4 model group (10% CCl4), CCl4 + low and high MFAEs groups (10% CCl4 + 100 mg/kg and 200 mg/kg MFAEs). We found that MFAEs decreased the kidney index of mice, restored the pathological changes of renal structure induced by CCl4, reduced cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (Kim-1) blood urea nitrogen and creatinine contents in serum, promoted the nuclear transportation of Nrf2 (nuclear factor erythroid derived 2 like 2), elevated the expression of HO-1 (heme oxygenase 1), GPX4 (glutathione peroxidase 4), SLC7A11 (solute carrier family 7 member 11), ZO-1 (zonula occludens-1) and Occludin, suppressed the expression of Keap1 (kelch-like ECH-associated protein 1), HMGB1 (High Mobility Group Protein 1), ACSL4 (acyl-CoA synthetase long chain family member 4) and TXNIP (thioredoxin interacting protein), upregulated the flora of Akkermansia, Anaerotruncus, Clostridium_sensu_stricto, Ihubacter, Alcaligenes, Dysosmobacter, and downregulated the flora of Clostridium_XlVa, Helicobacter, Paramuribaculum. Overlapped with Disbiome database, Clostridium_XlVa, Akkermansia and Anaerotruncus may be the potential genera treated with renal injury. It indicated that MFAEs could ameliorate kidney injury caused by CCl4 via Nrf2 signaling.

Improving Hybrid CTC/Attention Architecture for Agglutinative Language Speech Recognition.

Unlike the traditional model, the end-to-end (E2E) ASR model does not require speech information such as a pronunciation dictionary, and its system is built through a single neural network and obtains performance comparable to that of traditional methods. However, the model requires massive amounts of training data. Recently, hybrid CTC/attention ASR systems have become more popular and have achieved good performance even under low-resource conditions, but they are rarely used in Central Asian languages such as Turkish and Uzbek. We extend the dataset by adding noise to the original audio and using speed perturbation. To develop the performance of an E2E agglutinative language speech recognition system, we propose a new feature extractor, MSPC, which uses different sizes of convolution kernels to extract and fuse features of different scales. The experimental results show that this structure is superior to VGGnet. In addition to this, the attention module is improved. By using the CTC objective function in training and the BERT model to initialize the language model in the decoding stage, the proposed method accelerates the convergence of the model and improves the accuracy of speech recognition. Compared with the baseline model, the character error rate (CER) and word error rate (WER) on the LibriSpeech test-other dataset increases by 2.42% and 2.96%, respectively. We apply the model structure to the Common Voice-Turkish (35 h) and Uzbek (78 h) datasets, and the WER is reduced by 7.07% and 7.08%, respectively. The results show that our method is close to the advanced E2E systems.

Full-Length Transcriptome Characterization and Functional Analysis of Pathogenesis-Related Proteins in Lilium Oriental Hybrid 'Sorbonne' Infected with Botrytis elliptica.

Gray mold (Botrytis elliptica) causes a deleterious fungal disease that decreases the ornamental value and yield of lilies. Lilium oriental hybrid 'Sorbonne' is a variety that is resistant to gray mold. Understanding the mechanism of resistance against B. elliptica infection in 'Sorbonne' can provide a basis for the genetic improvement in lily plants. In this study, a PacBio Sequel II system was used to sequence the full-length transcriptome of Lilium 'Sorbonne' after inoculation with B. elliptica. A total of 46.64 Gb subreads and 19,102 isoforms with an average length of 1598 bp were obtained. A prediction analysis revealed 263 lncRNAs, and 805 transcription factors, 4478 simple sequence repeats, and 17,752 coding sequences were identified. Pathogenesis-related proteins (PR), which may play important roles in resistance against B. elliptica infection, were identified based on the full-length transcriptome data and previously obtained second-generation transcriptome data. Nine non-redundant potential LhSorPR proteins were identified and assigned to two groups that were composed of two LhSorPR4 and seven LhSorPR10 proteins based on their genetic relatedness. The real-time quantitative reverse transcription PCR (qRT-PCR) results showed that the patterns of expression of nine differentially expressed PR genes under B. elliptica stress were basically consistent with the results of transcriptome sequencing. The pattern of expression of LhSorPR4s and LhSorPR10s genes in different tissues was analyzed, and the expression of each gene varied. Furthermore, we verified the function of LhSorPR4-2 gene in Lilium. The expression of LhSorPR4-2 was induced by phytohormones such as methyl jasmonate, salicylic acid, and ethephon. Moreover, the promoter region of LhSorPR4-2 was characterized by several functional domains associated with phytohormones and stress response. The overexpression of LhSorPR4-2 gene in 'Sorbonne' increased the resistance of the lily plant to B. elliptica and correlated with high chitinase activity. This study provides a full-length transcript database and functionally analyzed the resistance of PR gene to B. elliptica in Lilium, thereby introducing the candidate gene LhSorPR4-2 to breed resistance in Lilium.

Oxidative stress-modulating drugs have preferential anticancer effects - involving the regulation of apoptosis, DNA damage, endoplasmic reticulum stress, autophagy, metabolism, and migration.

To achieve preferential effects against cancer cells but less damage to normal cells is one of the main challenges of cancer research. In this review, we explore the roles and relationships of oxidative stress-mediated apoptosis, DNA damage, ER stress, autophagy, metabolism, and migration of ROS-modulating anticancer drugs. Understanding preferential anticancer effects in more detail will improve chemotherapeutic approaches that are based on ROS-modulating drugs in cancer treatments.

Impact of hydrogen dopant incorporation on InGaZnO, ZnO and In2O3 thin film transistors.

In this work, hydrogen (H) plasma treatment is implemented to dope indium gallium zinc oxide (InGaZnO), zinc oxide (ZnO), and indium oxide (In2O3) thin-film transistors (TFTs). We systematically analyze the active defect states inside these n-type metal oxides and reveal how they are impacted by H dopant incorporation, combining the device transfer characteristics (including the threshold voltage, subthreshold slope, and carrier mobility), the X-ray photoelectron spectra, and numerical and theoretical investigations. An increase of the field-effect mobility of these TFTs is mainly attributed to the decreased interface and bulk tail-distributed traps, after an appropriate amount of H dopants is incorporated. In ZnO, hydrogen exclusively acts as a shallow donor during the plasma treatment, while the zinc vacancies Zn(Vac) cannot be passivated by the H dopants as no improvement of the subthreshold slope (SS) is observed in the hydrogenated ZnO TFT. The H interstitials (Hi) incorporated into In2O3 are stable in the + charge state at equilibrium, then change into the - charge state as the Fermi level energy EF gets closer to the bottom of the conduction band. Due to the H insertion into an oxygen vacancy VO, the VOH complex (acting as an acceptor) is formed in InGaZnO with increased H plasma treatment duration, leading to the degraded SS. This paper clarifies the H dopants' role and the different dominant defects inside the three types of TFTs, which may benefit systematic understanding and exploration of H dopant incorporation into InGaZnO, ZnO and In2O3 films for TFT improvement and optimization.

Antimycin A shows selective antiproliferation to oral cancer cells by oxidative stress-mediated apoptosis and DNA damage.

The antibiotic antimycin A (AMA) is commonly used as an inhibitor for the electron transport chain but its application in anticancer studies is rare. Recently, the repurposing use of AMA in antiproliferation of several cancer cell types has been reported. However, it is rarely investigated in oral cancer cells. The purpose of this study is to investigate the selective antiproliferation ability of AMA treatment on oral cancer cells. Cell viability, flow cytometry, and western blotting were applied to explore its possible anticancer mechanism in terms of both concentration- and exposure time-effects. AMA shows the higher antiproliferation to two oral cancer CAL 27 and Ca9-22 cell lines than normal oral HGF-1 cell lines. Moreover, AMA induces the production of higher reactive oxygen species (ROS) levels and pan-caspase activation in oral cancer CAL 27 and Ca9-22 cells than in normal oral HGF-1 cells, providing the possible mechanism for its selective antiproliferation effect of AMA. In addition to ROS, AMA induces mitochondrial superoxide (MitoSOX) generation and depletes mitochondrial membrane potential (MitoMP). This further supports the AMA-induced oxidative stress changes in oral cancer CAL 27 and Ca9-22 cells. AMA also shows high expressions of annexin V in CAL 27 and Ca9-22 cells and cleaved forms of poly (ADP-ribose) polymerase (PARP), caspase 9, and caspase 3 in CAL 27 cells, supporting the apoptosis-inducing ability of AMA. Furthermore, AMA induces DNA damage (γH2AX and 8-oxo-2'-deoxyguanosine [8-oxodG]) in CAL 27 and Ca9-22 cells. Notably, the AMA-induced selective antiproliferation, oxidative stress, and DNA damage were partly prevented from N-acetylcysteine (NAC) pretreatments. Taken together, AMA selectively kills oral cancer cells in an oxidative stress-dependent mechanism involving apoptosis and DNA damage.

Twelve Chinese herbal preparations for the treatment of depression or depressive symptoms in cancer patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients with cancer are vulnerable to depression or other depressive conditions. The aim of this paper was to evaluate the efficacy and safety of Chinese herbal medicine (CHM) for the treatment of depression or depressive symptoms in cancer patients. METHODS: CENTRAL, MEDLINE, EMBASE, PsycINFO, CNKI, VIP, SinoMed, and online clinical trial registry websites were searched for relevant RCTs until May 2017. The methodological quality of each included study was assessed with the "risk of bias" tool. Review Manager 5.3.5 was used to analyze the data. RESULTS: We identified 18 RCTs that included data from 1441 participants. Twelve different types of Chinese herbal preparations were investigated by these studies, and they showed a better therapeutic effect in most comparisons when measured in terms of depression rating scale scores, with SMDs (95% CI) of - 2.30 (- 3.54, - 1.05) (CHM versus no treatment), - 0.61 (- 1.03, - 0.18) (CHM versus antidepressants), and - 0.55 (- 1.07, - 0.02) (CHM plus psychological treatments versus psychological treatments), or when measured in terms of treatment response rate, with RRs (95% CI) of 1.65 (1.19, 2.29) (CHM versus no treatment), 1.15 (1.03, 1.28) (CHM versus psychological treatments), 1.32 (1.07, 1.63) (CHM plus antidepressants versus antidepressants), and 1.70 (1.02, 2.85) (CHM plus psychological treatments versus psychological treatments). Compared with antidepressants, these CHMs showed borderline superiority for improving the response rate, with an RR (95% CI) of 1.08 (0.93, 1.26). Subgroup analysis based on psychiatric diagnosis (depression versus depressive symptoms) did not modify the direction of these estimates and neither could it explain the high level of heterogeneity. Patients in the CHM group experienced fewer adverse events of cardiac toxicity (P = 0.02), functional gastrointestinal disorders (P = 0.008), sleep disturbances (P = 0.02), blurred vision (P = 0.02) and fatigue (P = 0.03) than the patients in the no treatment group or the antidepressants group. CONCLUSIONS: According to the investigation of the twelve herbal preparations, the CHM intervention appears to alleviate depressive symptoms in cancer patients, either alone or combined with antidepressants or psychological treatments. However, a high risk of bias and high heterogeneity made the mean estimates uncertain. Well-designed trials with comprehensive and transparent reporting are warranted in the future.

LY303511 displays antiproliferation potential against oral cancer cells in vitro and in vivo.

LY303511 was developed as a negative control of LY294002 without pan-phosphoinositide 3-kinase (PI3K) inhibition. We hypothesize LY303511 generate reactive oxygen species (ROS) to induce apoptosis for killing oral cancer cells. In MTS assay, LY303511 dose-responsively decreases survival in three kinds of oral cancer cells but little damage to normal oral cells (HGF-1). Two oral cancer cells (CAL 27 and SCC-9) with highly sensitivity to LY303511 were used. In 7-aminoactinomycin D (7AAD) assay, LY303511 slightly increases subG1 population in oral cancer cells. In annexin V/7AAD and/or pancaspase assays, LY303511 induces apoptosis in oral cancer cells but HGF-1 cells remains in basal level. In oxidative stress, LY303511 induces ROS and mitochondrial superoxide in oral cancer cells. In 8-oxo-2'-deoxyguanosine assay, LY303511 induces oxidative DNA damage in oral cancer cells. In zebrafish model, LY303511 inhibits CAL 27-xenografted tumor growth. Therefore, LY303511 displays antiproliferation potential against oral cancer cells in vitro and in vivo.

4ß-Hydroxywithanolide E selectively induces oxidative DNA damage for selective killing of oral cancer cells.

Reactive oxygen species (ROS) induction had been previously reported in 4ß-hydroxywithanolide (4ßHWE)-induced selective killing of oral cancer cells, but the mechanism involving ROS and the DNA damage effect remain unclear. This study explores the role of ROS and oxidative DNA damage of 4ßHWE in the selective killing of oral cancer cells. Changes in cell viability, morphology, ROS, DNA double strand break (DSB) signaling (γH2AX foci in immunofluorescence and DSB signaling in western blotting), and oxidative DNA damage (8-oxo-2'deoxyguanosine [8-oxodG]) were detected in 4ßHWE-treated oral cancer (Ca9-22) and/or normal (HGF-1) cells. 4ßHWE decreased cell viability, changed cell morphology and induced ROS generation in oral cancer cells rather than oral normal cells, which were recovered by a free radical scavenger N-acetylcysteine (NAC). For immunofluorescence, 4ßHWE also accumulated more of the DSB marker, γH2AX foci, in oral cancer cells than in oral normal cells. For western blotting, DSB signaling proteins such as γH2AX and MRN complex (MRE11, RAD50, and NBS1) were overexpressed in 4ßHWE-treated oral cancer cells in different concentrations and treatment time. In the formamidopyrimidine-DNA glycolyase (Fpg)-based comet assay and 8-oxodG-based flow cytometry, the 8-oxodG expressions were higher in 4ßHWE-treated oral cancer cells than in oral normal cells. All the 4ßHWE-induced DSB and oxidative DNA damage to oral cancer cells were recovered by NAC pretreatment. Taken together, the 4ßHWE selectively induced DSB and oxidative DNA damage for the ROS-mediated selective killing of oral cancer cells.

A systematic review and meta-analysis of randomized controlled trials: Skin-patch of Chinese herbal medicine for patients with acute gouty arthritis.

AIMS: To evaluate the evidence of the effectiveness and safety of Chinese herbal medicine skin-patches for patients with acute gouty arthritis. BACKGROUND: Acute gouty arthritis is a problem that can limit the level of activity and impair the quality of life. In China, many clinical studies have demonstrated that skin-patches of Chinese herbal medicines benefit patients with acute gouty arthritis. However, the reported clinical effects vary. DESIGN: A systematic review and meta-analysis of randomized controlled trials. DATA SOURCES: Three English databases including CENTRAL (1993 to February 2017), PubMed (1966 to February 2017) and EMBASE (1974 to February 2017) and four Chinese databases including Chinese National Knowledge Infrastructure, Chinese VIP Information, SinoMed and Wanfang (all, 1949 - February 2017) were searched. Randomized controlled trials that compared skin-patches of Chinese herbal medicine with or without conventional treatments to conventional treatments, no treatment or a placebo treatment for patients with acute gouty arthritis were included. REVIEW METHODS: We conducted a systematic review and meta-analysis following the Cochrane process. Two authors selected the studies, extracted the data and evaluated the risk of bias of the included trials. RESULTS: Nineteen studies met our inclusion criteria. After synthesizing the data, the results showed that skin-patches of CHM combined with Western medicine seemed to be more effective than Western medicine alone for pain relief in patients with acute gouty arthritis and had fewer adverse events. CONCLUSION: Due to the quality of the data, larger and more rigorously designed clinical trials with proper outcome measures are necessary.

Correction: Huang, H.W.; et al. Sinularin Selectively Kills Breast Cancer Cells Showing G2/M Arrest, Apoptosis, and Oxidative DNA Damage. Molecules 2018, 23, 849.

The authors wish to make the following correction to their paper [1].[...].