Partial Alleviation of Homologous Superinfection Exclusion of SeMNPV Latently Infected Cells by G1 Phase Infection and G2/M Phase Arrest.

Viral infection can regulate the cell cycle, thereby promoting viral replication. Hijacking and altering the cell cycle are important for the virus to establish and maintain a latent infection. Previously, Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV)-latently infected P8-Se301-C1 cells, which grew more slowly than Se301 cells and interfered with homologous SeMNNPV superinfection, were established. However, the effects of latent and superinfection with baculoviruses on cell cycle progression remain unknown. In this study, the cell cycle profiles of P8-Se301-C1 cells and SeMNPV or Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-infected P8-Se301-C1 cells were characterized by flow cytometry. The results showed that replication-related genes MCM4, PCNA, and BAF were down-regulated (p < 0.05) in P8-Se301-C1 cells, and the S phase of P8-Se301-C1 cells was longer than that of Se301 cells. P8-Se301-C1 cells infected with SeMNPV did not arrest in the G2/M phase or affect the expression of Cyclin B and cyclin-dependent kinase 1 (CDK1). Furthermore, when P8-Se301-C1 cells were infected with SeMNPV after synchronized treatment with hydroxyurea and nocodazole, light microscopy and qRT-PCR analysis showed that, compared with unsynchronized cells and S and G2/M phase cells, SeMNPV-infected P8-Se301-C1 cells in G1 phase induced G2/M phase arrest, and the amount of virus adsorption and intracellular viral DNA replication were significantly increased (p < 0.05). In addition, budded virus (BV) production and occlusion body (OB)-containing cells were both increased at 120 h post-infection (p < 0.05). The expression of Cyclin B and CDK1 was significantly down-regulated at 48 h post-infection (p < 0.05). Finally, the arrest of SeMNPV-infected G1 phase cells in the G2/M phase increased BV production (p < 0.05) and the number of OB-containing cells. In conclusion, G1 phase infection and G2/M arrest are favorable to SeMNPV proliferation in P8-Se301-C1 cells, thereby alleviating the homologous superinfection exclusion. The results contribute to a better understanding of the relationship between baculoviruses and insect cell cycle progression and regulation.

Cucurbitacin B suppresses hepatocellular carcinoma progression through inducing DNA damage-dependent cell cycle arrest.

BACKGROUND: The mortality rate of liver cancer ranks third in the world, and hepatocellular carcinoma (HCC) is a malignant tumor of the digestive tract. Cucurbitacin B (CuB), a natural compound extracted from Cucurbitaceae spp., is the main active component of Chinese patent medicine the Cucurbitacin Tablet, which has been widely used in the treatment of various malignant tumors in clinics, especially HCC. PURPOSE: This study explored the role and mechanism of CuB in the suppression of liver cancer progression. METHODS: Cell Counting Kit-8 (CCK-8) and colony formation assays were used to detect the inhibitory function of CuB in Huh7, Hep3B, and Hepa1/6 hepatoma cells. Calcein-AM/propidium iodide (PI) staining and lactate dehydrogenase (LDH) measurement assays were performed to determine cell death. Mitochondrial membrane potential (Δψm) was measured, and flow cytometry was performed to evaluate cell apoptosis and cell cycle. Several techniques, such as proteomics, Western blotting (WB), and ribonucleic acid (RNA) interference, were utilized to explore the potential mechanism. The animal experiment was performed to verify the results of in vitro experiments. RESULTS: CuB significantly inhibited the growth of Huh7, Hep3B, and Hepa1/6 cells and triggered the cell cycle arrest in G2/M phage without leading to cell death, especially apoptosis. Knockdown of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a target of CuB, did not reverse CuB elicited cell cycle arrest. CuB enhanced phosphorylated ataxia telangiectasia mutated (p-ATM) and phosphorylated H2A histone family member X (γ-H2AX) levels. Moreover, CuB increased p53 and p21 levels and decreased cyclin-dependent kinase 1 (CDK1) expression, accompanied by improving phosphorylated checkpoint kinase 1 (p-CHK1) level and suppressing cell division cycle 25C (CDC25C) protein level. Interestingly, these phenomena were partly abolished by a deoxyribonucleic acid (DNA) protector methylproamine (MPA). Animal studies showed that CuB also significantly suppressed tumor growth in BALB/c mice bearing Hepa1/6 cells. In tumor tissues, CuB reduced the expression levels of proliferating cell nuclear antigen (PCNA) and γ-H2AX but did not change the terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) level. CONCLUSION: This study demonstrated for the first time that CuB could effectively impede HCC progression by inducing DNA damage-dependent cell cycle arrest without directly triggering cell death, such as necrosis and apoptosis. The effect was achieved through ataxia telangiectasia mutated (ATM)-dependent p53-p21-CDK1 and checkpoint kinase 1 (CHK1)-CDC25C signaling pathways. These findings indicate that CuB may be used as an anti-HCC drug, when the current findings are confirmed by independent studies and after many more clinical phase 1, 2, 3, and 4 testings have been done.

Compound-composed Chinese medicine of Huachansu triggers apoptosis of gastric cancer cells through increase of reactive oxygen species levels and suppression of proteasome activities.

BACKGROUND: Huachansu (HCS), a known Chinese patent drug extracted from the Chinese toad skin, is frequently used for the treatment of various advanced cancers, especially gastric cancer, due to the good therapeutic effect. However, it is rather difficult to clarify the active substances and molecular mechanisms involved owing to the lack of appropriate research strategies. We recently proposed the concept and research ideas of compound-composed Chinese medicine formula. PURPOSE: To discover compound-composed Chinese medicine from Huachansu and to explore its mechanism of action in inducing apoptosis of gastric cancer cells. METHOD: Network pharmacology combined with serum pharmacochemistry was utilized to screen the predominant active constituents from HCS against gastric cancer. Then, the compound-composed Chinese medicine of HCS (CCMH) was prepared according to their relative contents in serum. The pharmacological effects and potential mechanisms for CCMH were investigated by assays for cell viability, cell cycle, apoptosis, mitochondrial membrane potential (MMP), proteomics, reactive oxygen species (ROS), N-Acetylcysteine (NAC) antagonism, proteasome activity, and western blot. RESULTS: CCMH was comprised of arenobufagin (11.14%), bufalin (18.67%), bufotalin (7.33%), cinobufagin (16.67%), cinobufotalin (16.74%), gamabufotalin (8.45%), resibufogenin (12.03%), and telocinobufagin (8.97%). CCMH evidently induced proliferation inhibition, cell cycle arrest, apoptosis, and MMP collapse in gastric cancer cells, possessing the better activities than HCS. Proteomic analysis showed that CCMH influenced ROS pathway, ubiquitin proteasome system, and PI3K/Akt and MAPK signaling pathways. CCMH markedly enhanced intracellular ROS levels in gastric cancer cells, which was reversed by NAC. Accordingly, NAC antagonized the apoptosis-inducing effect of CCMH. Significantly decreased proteasome 20S activity by CCMH was observed in gastric cancer cells. CCMH also regulated the expression of key proteins in PI3K/Akt and MAPK signaling pathways. CONCLUSION: CCMH possesses more significant apoptotic induction effects on gastric cancer cells than HCS, which is achieved primarily through suppression of proteasome activities and increase of ROS levels, followed by regulating PI3K/Akt and MAPK signaling pathways. Network pharmacology combined with serum pharmacochemistry is an effective strategy for discovering compound-composed Chinese medicine from traditional Chinese medicine, which can help clarify the pharmacological substances and mechanisms of action for traditional Chinese medicine.

CXCL6: A potential therapeutic target for inflammation and cancer.

Chemokines were originally defined as cytokines that affect the movement of immune cells. In recent years, due to the increasing importance of immune cells in the tumor microenvironment (TME), the role of chemokines has changed from a single "chemotactic agent" to a key factor that can regulate TME and affect the tumor phenotype. CXCL6, also known as granulocyte chemoattractant protein-2 (GCP-2), can recruit neutrophils to complete non-specific immunity in the process of inflammation. Cancer-related genes and interleukin family can promote the abnormal secretion of CXCL6, which promotes tumor growth, metastasis, epithelial mesenchymal transformation (EMT) and angiogenesis in the TME. CXCL6 also has a role in promoting fibrosis and tissue damage repair. In this review, we focus on the regulatory network affecting CXCL6 expression, its role in the progress of inflammation and how it affects tumorigenesis and progression based on the TME, in an attempt to provide a potential target for the treatment of diseases such as inflammation and cancer.

Immuno-genomic-radiomics to predict response of biliary tract cancer to camrelizumab plus GEMOX in a single-arm phase II trial.

Background & Aims: Immunotherapy is an option for the treatment of advanced biliary tract cancer (BTC), although it has a low response rate. In this post hoc analysis, we investigated the predictive value of an immuno-genomic-radiomics (IGR) analysis for patients with BTC treated with camrelizumab plus gemcitabine and oxaliplatin (GEMOX) therapy. Methods: Thirty-two patients with BTC treated with camrelizumab plus GEMOX were prospectively enrolled. The relationship between high-throughput computed tomography (CT) radiomics features with immuno-genomic expression was tested and scaled with a full correlation matrix analysis. Odds ratio (OR) of IGR expression for objective response to camrelizumab plus GEMOX was tested with logistic regression analysis. Association of IGR expression with progression-free survival (PFS) and overall survival (OS) was analysed with a Cox proportional hazard regression. Results: CT radiomics correlated with CD8+ T cells (r = -0.72-0.71, p = 0.004-0.047), tumour mutation burden (TMB) (r = 0.59, p = 0.039), and ARID1A mutation (r = -0.58-0.57, p = 0.020-0.034). There was no significant correlation between radiomics and programmed cell death protein ligand 1 expression (p >0.96). Among all IGR biomarkers, only four radiomics features were independent predictors of objective response (OR = 0.09-3.81; p = 0.011-0.044). Combining independent radiomics features into an objective response prediction model achieved an area under the curve of 0.869. In a Cox analysis, radiomics signature [hazard ratio (HR) = 6.90, p <0.001], ARID1A (HR = 3.31, p = 0.013), and blood TMB (HR = 1.13, p = 0.023) were independent predictors of PFS. Radiomics signature (HR = 6.58, p <0.001) and CD8+ T cells (HR = 0.22, p = 0.004) were independent predictors of OS. Prognostic models integrating these features achieved concordance indexes of 0.677 and 0.681 for PFS and OS, respectively. Conclusions: Radiomics could act as a non-invasive immuno-genomic surrogate of BTC, which could further aid in response prediction for patients with BTC treated with immunotherapy. However, multicenter and larger sample studies are required to validate these results. Impact and implications: Immunotherapy is an alternative for the treatment of advanced BTC, whereas tumour response is heterogeneous. In a post hoc analysis of the single-arm phase II clinical trial (NCT03486678), we found that CT radiomics features were associated with the tumour microenvironment and that IGR expression was a promising marker for tumour response and long-term survival. Clinical trial number: Post hoc analysis of NCT03486678.

Natural products targeting macrophages in tumor microenvironment are a source of potential antitumor agents.

BACKGROUND: Macrophages are one of the major cell types in the immune system and are closely related to tumor development, which can be polarized into M1 type with anti-tumor activity or M2 type with pro-tumor activity. The infiltration of more macrophages into tumor predicts poorer prognosis due to their more exhibition of M2 phenotype under the influence of many factors in the tumor microenvironment (TME). Therefore, reverse of M2 macrophage polarization in TME is conducive to the suppression of tumor deterioration and understanding the influencing factors of macrophage polarization is helpful to provide new ideas for the subsequent targeting macrophages for tumor therapy. PURPOSE: This review summarizes the effects of TME on macrophage polarization and natural products against M2 macrophage polarization, which may provide some directions for tumor therapy. METHODS: The search of relevant literature was conducted using the PubMed, Science Direct, CNKI and Web of Science databases with the search terms "macrophage", "tumor microenvironment", "natural product" and "tumor". RESULTS: The mutual transformation of M1 and M2 phenotypes in macrophages is influenced by many factors. Tumor cells affect the polarization of macrophages by regulating the expression of genes and proteins and the secretion of cytokines. The expression of some genes or proteins in macrophages is also related to their own polarization. Many natural products can reverse M2 polarization of macrophages which has been summarized in this review. CONCLUSION: Regulation of macrophage polarization in TME can inhibit tumor development, and natural products have the potential to impede tumor development by regulating macrophage polarization.

Effectiveness of peripheral defocus spectacle lenses in myopia control: a Meta-analysis and systematic review.

AIM: To evaluate the effectiveness of peripheral defocus spectacle lenses (PDLs) in myopia control. METHODS: Literature retrieval on PubMed, Cochrane Library, Embase, and Web of Science databases, and the search time limit was from the establishment of each database to December 29, 2021 were conducted. Change of spherical equivalent refraction (SER) and axial change (AL) were extracted from the literatures that met the inclusion criteria, and RevMan5.3 software was used for Meta-analysis. RESULTS: A total of 4 randomized controlled trials (RCTs) were included in this Meta-analysis, involving 770 myopic children. The results showed that PDLs could delay the progression of myopia in children with myopia compared with single vision spectacle lenses (SVLs; WMD=0.21 D, 95%CI: 0.01, 0.41, P=0.04). However, there was no significant difference in controlling the growth of axial length (AL) in myopic children (WMD=-0.10 mm, 95%CI: -0.21, 0.01, P=0.07). The results of the effectiveness of myopia control between the two spectacle lenses showed that PDLs were more effective in controlling the progression of myopia (OR=5.73, 95%CI: 2.58, 12.70, P<0.001) and delaying the growth of AL (OR=44.25, 95%CI: 8.84, 221.58, P<0.001) than SVLs, and the differences were statistically significant. CONCLUSION: PDLs can control the progression of myopia compared with SVLs, but cannot delay the growth of AL, and the effectiveness of PDLs in myopia control better than SVLs.

TED: Two-stage expert-guided interpretable diagnosis framework for microvascular invasion in hepatocellular carcinoma.

Microvascular invasion (MVI) has been clinically recognized as a prognostic factor for hepatocellular carcinoma (HCC) after surgical treatment. Detection of MVI before surgical operation greatly benefit patients' prognosis and survival. Most of the existing methods for automatic diagnosis of MVI directly use deep neural networks to make predictions, which do not take into account clinical knowledge and lack of interpretability. To simulate the radiologists' decision process, this paper proposes a Two-stage Expert-guided Diagnosis (TED) framework for MVI in HCC. Specifically, the first stage aims to predict key imaging attributes for MVI diagnosis, and the second stage leverages these predictions as a form of attention as well as soft supervision through a variant of triplet loss, to guide the fitting of the MVI diagnosis network. The attention and soft supervision are expected to jointly guide the network to learn more semantically correlated representations and thereafter increase the interpretability of the diagnosis network. Extensive experimental analysis on a private dataset of 466 cases has shown that the proposed method achieves 84.58% on AUC and 84.07% on recall, significantly exceeding the baseline methods.

LiSNet: An artificial intelligence -based tool for liver imaging staging of hepatocellular carcinoma aggressiveness.

BACKGROUND: Presurgical assessment of hepatocellular carcinoma (HCC) aggressiveness can benefit patients' treatment options and prognosis. PURPOSE: To develop an artificial intelligence (AI) tool, namely, LiSNet, in the task of scoring and interpreting HCC aggressiveness with computed tomography (CT) imaging. METHODS: A total of 358 patients with HCC undergoing curative liver resection were retrospectively included. Three subspecialists were recruited to pixel-wise annotate and grade tumor aggressiveness based on CT imaging. LiSNet was trained and validated in 193 and 61 patients with a deep neural network to emulate the diagnostic acumen of subspecialists for staging HCC. The test set comprised 104 independent patients. We subsequently compared LiSNet with an experience-based binary diagnosis scheme and human-AI partnership that combined binary diagnosis and LiSNet for assessing tumor aggressiveness. We also assessed the efficiency of LiSNet for predicting survival outcomes. RESULTS: At the pixel-wise level, the agreement rate of LiSNet with subspecialists was 0.658 (95% confidence interval [CI]: 0.490-0.779), 0.595 (95% CI: 0.406-0.734), and 0.369 (95% CI: 0.134-0.566), for scoring HCC aggressiveness grades I, II, and III, respectively. Additionally, LiSNet was comparable to subspecialists for predicting histopathological microvascular invasion (area under the curve: LiSNet: 0.668 [95% CI: 0.559-0.776] versus subspecialists: 0.699 [95% CI: 0.591-0.806], p > 0.05). In a human-AI partnered diagnosis, combining LiSNet and experience-based binary diagnosis can achieve the best predictive ability for microvascular invasion (area under the curve: 0.705 [95% CI: 0.589-0.820]). Furthermore, LiSNet was able to indicate overall survival after surgery. CONCLUSION: The designed LiSNet tool warrants evaluation as an alternative tool for radiologists to conduct automatic staging of HCC aggressiveness at the pixel-wise level with CT imaging. Its prognostic value might benefit patients' treatment options and survival prediction.

Comparison of intravitreal aflibercept and dexamethasone implant in the treatment of macular edema associated with diabetic retinopathy or retinal vein occlusion: a Meta-analysis and systematic review.

AIM: To compare the efficacy and safety of intravitreal aflibercept with dexamethasone implant in the treatment of macular edema (ME) associated with diabetic retinopathy (DR) or retinal vein occlusion (RVO). METHODS: A comprehensive search of studies comparing dexamethasone and aflibercept in patients with ME was conducted at PubMed, Embase, and Cochrane Central Register of Controlled Trials from the beginning of library to April 16, 2021. Extracting the data including best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of injections and serious adverse events (SAEs) from the final qualified articles. RevMan 5.3 software was used for Meta-analysis of the included studies. RESULTS: Totally 7 studies with 369 eyes were included. The causes of ME in the final screening study included RVO and DR. Compared with the aflibercept treatment group, the BCVA of the dexamethasone implant treatment group showed no significant difference in the follow-up for 3mo [mean difference (MD): -0.05, 95% confidence interval (CI): -0.11, 0.02; P=0.17] and 12mo (MD: -0.01, 95%CI: -0.38, 0.37; P=0.98), but it was slightly worse than the aflibercept group at 6mo (MD: 0.12, 95%CI: 0.03, 0.21; P=0.008). In terms of CRT reduction, there was no significant difference between the two groups at 3mo (MD: -28.14, 95%CI: -79.95, 23.67; P=0.29), 6mo (MD: 27.67, 95%CI: -84.89, 140.24; P=0.63), and 12mo (MD: -59.00, 95%CI: -127.37, 9.37; P=0.09). However, dexamethasone implant had fewer injections, but more adverse events such as elevated intraocular pressure (IOP) and cataract. CONCLUSION: Intravitreal injection of aflibercept and dexamethasone implant can both effectively increase BCVA and reduce CRT. Compared with aflibercept, dexamethasone implant is not inferior in improving vision and reducing CRT in the initial treatment period (3mo) and long-term treatment period (12mo). Besides, it has fewer injections and more likely to cause elevated IOP and cataract.

Forsythiasides: A review of the pharmacological effects.

Forsythiasides are a kind of phenylethanol glycosides existing in Forsythia suspensa (Thunb.) Vahl, which possesses extensive pharmacological activities. According to the different groups connected to the nucleus, forsythiasides can be divided into A-K. In recent years, numerous investigations have been carried out on forsythiasides A, B, C, D, E, and I, which have the effects of cardiovascular protection, anti-inflammation, anti-oxidation, neuroprotection, et al. Mechanistically, forsythiasides regulate toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappaB (NF-κB), nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and other signaling pathways, as well as the expression of related cytokines and kinases. Further exploration and development may unearth more treatment potential of forsythiasides and provide more evidence for their clinical applications. In summary, forsythiasides have high development and application value.

Bie-Jia-Ruan-Mai-Tang, a Chinese Medicine Formula, Inhibits Retinal Neovascularization in Diabetic Mice Through Inducing the Apoptosis of Retinal Vascular Endothelial Cells.

Proliferative diabetic retinopathy (PDR) is one of the main complications of diabetes, mainly caused by the aberrant proliferation of retinal vascular endothelial cells and the formation of new blood vessels. Traditional Chinese medicines possess great potential in the prevention and treatment of PDR. Bie-Jia-Ruan-Mai-Tang (BJ), a Chinese medicine formula, has a good therapeutic effect on PDR clinically; however, the mechanism of action involved remains unclear. Therefore, we investigated the effect of BJ on PDR through in vitro and in vivo experiments. A diabetic mouse model with PDR was established by feeding a high-fat-high-glucose diet combined with an intraperitoneal injection of streptozotocin (STZ), while high-glucose-exposed human retinal capillary endothelial cells (HRCECs) were employed to mimic PDR in vitro. The in vivo experiments indicated that BJ inhibited the formation of acellular capillaries, decreased the expression of VEGF, and increased the level of ZO-1 in diabetic mice retina. In vitro experiments showed that high glucose significantly promoted cell viability and proliferation. However, BJ inhibited cell proliferation by cycle arrest in the S phase, thus leading to apoptosis; it also increased the production of ROS, decreased the mitochondrial membrane potential, reduced the ATP production, and also reduced the expressions of p-PI3K, p-AKT, and Bcl-xL, but increased the expressions of Bax and p-NF-κB. These results suggest that BJ induces the apoptosis of HRCECs exposed to high glucose through activating the mitochondrial death pathway by decreasing the PI3K/AKT signaling and increasing the NF-κB signaling to inhibit the formation of acellular capillaries in the retina, thus impeding the development of PDR.

Efficacy evaluation of intravitreal ranibizumab therapy for three types of retinopathy of prematurity.

AIM: To evaluate efficacy of intravitreal ranibizumab (IVR) therapy for aggressive posterior retinopathy of prematurity (ROP), threshold ROP disease and type 1 pre-threshold ROP. METHODS: A retrospective analysis was performed on 40 patients (76 eyes) who had IVR as the primary treatment for ROP from April 2017 to January 2018. According to disease pathogenic features, the 76 eyes were divided into three groups: aggressive posterior ROP (AP-ROP) group (16 eyes), threshold ROP group (28 eyes) and type 1 pre-threshold ROP group (32 eyes). The characteristics of patients and lesions situation before the first intravitreal injection, and posttreatment fundus outcomes determined by wide-angle RetCam fundus imaging were recorded. RESULTS: The birth weight and postmenstrual age of first IVR treatment in AP-ROP, threshold ROP, and type 1 pre-threshold ROP groups were significant difference (1087.50±246.78, 1103.75±168.30, 1257.03±210.82 g, P=0.005; 34.50±1.46, 36.89±2.97, 36.50±2.36wk, P=0.008), while the gestational age was not difference (28.00±2.00, 28.54±1.90, 28.59±1.43wk, P=0.510). The retina hemorrhage ratio (with/without: 14/2, 8/20, 5/27), iris neovascularization or vascular engorgement ratio (with/without: 12/4, 11/17, 6/26), and the zone I (inside/outside: 16/0, 2/26, 5/27) in AP-ROP, threshold ROP, and type 1 pre-threshold ROP group were difference significantly (all P<0.05). The regression rates were 37.5%, 92.86%, and 100%, and the recurrence rates were 62.5%, 7.14%, and 0 in AP-ROP, threshold ROP, and type 1 pre-threshold ROP group, respectively (both P<0.05). The recurrence eyes were cured by secondary IVR or retinal laser photocoagulation. CONCLUSION: IVR is an effective treatment for all types of ROP. The regression of AP-ROP is significantly lower than type 1 pre-threshold and threshold disease. Birth weight, retinal hemorrhage, iris neovascularization or vascular engorgement and lesions located in zone I may be associated with AP-ROP recurrence and retreatment, which should be noted in follow-up.

Ginsenoside Rd: A promising natural neuroprotective agent.

BACKGROUND: Neurological diseases seriously affect human health, which are arousing wider attention, and it is a great challenge to discover neuroprotective drugs with minimal side-effects and better efficacies. Natural agents derived from herbs or plants have become unparalleled resources for the discovery of novel drug candidates. Panax ginseng C. A. Meyer, a well-known herbal medicine in China, occupies a very important position in traditional Chinese medicines (TCMs) with a long history of clinical application. Ginsenoside Rd is the active compound in P. ginseng known to have broad-spectrum pharmacological effects to reduce neurological damage that can lead to neurological diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, depression, cognitive impairment, and cerebral ischemia. PURPOSE: To review and discuss the effects and mechanisms of ginsenoside Rd in the treatment of neurological diseases. STUDY DESIGN & METHODS: The related information was compiled by the major scientific databases, such as Chinese National Knowledge Infrastructure (CNKI), Elsevier, ScienceDirect, PubMed, SpringerLink, Web of Science, and GeenMedical. Using 'Ginsenoside Rd', 'Ginsenosides', 'Anti-inflammation', 'Antioxidant', 'Apoptosis' and 'Neuroprotection' as keywords, the correlated literature was extracted and conducted from the databases mentioned above. RESULTS: Through summarizing the existing research progress, we found that the general effects of ginsenoside Rd are anti-inflammatory, antioxidant, anti-apoptosis, inhibition of Ca2+ influx and protection of mitochondria, and through these pathways, the compound can inhibit excitatory toxicity, regulate nerve growth factor, and promote nerve regeneration. CONCLUSION: Ginsenoside Rd is a promising natural neuroprotective agent. This review would contribute to the future development of ginsenoside Rd as a novel clinical candidate drug for treating neurological diseases.

Radiomics analysis of pretreatment MRI in predicting tumor response and outcome in hepatocellular carcinoma with transarterial chemoembolization: a two-center collaborative study.

BACKGROUND AND OBJECTIVE: To develop a machine-learning model by integrating clinical and imaging modalities for predicting tumor response and survival of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE). METHODS: 140 HCC patients with TACE were retrospectively included from two centers. Tumor response were evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Response-related radiomics scores (Rad-scores) were constructed on T2-weighted images (T2WI) and dynamic contrast-enhanced (DCE) imaging separately, and then integrated with conventional clinic-radiological variables into a logistic regression (LR) model for predicting tumor response. LR model was trained in 94 patients in center 1 and independently tested in 46 patients in center 2. RESULTS: Among 4 MRI sequences, T2WI achieved better performance than DCE (area under the curve [AUC] 0.754 vs 0.602 to 0.752). LR model by combining Rad-score on T2WI with Barcelona Clinic Liver Cancer (BCLC) stage and albumin-bilirubin (ALBI) grade resulted in an AUC of 0.813 in training and 0.781 in test for predicting tumor response. In survival analysis, progression-free survival (PFS) and overall survival (OS) presented significant difference between LR-predicted responders and non-responders. The ALBI grade and BCLC stage were independent predictors of PFS; and LR-predicted response, ALBI grade, satellite node, and BCLC stage were independent predictors of OS. The resulting Cox model produced concordance-indexes of 0.705 and 0.736 for predicting PFS and OS, respectively. CONCLUSIONS: The model combined MRI radiomics with clinical factors demonstrated favorable performance for predicting tumor response and clinical outcomes, thus may help personalized clinical management.

Circular RNA-CDR1as is involved in lung injury induced by long-term formaldehyde inhalation.

OBJECTIVE: Formaldehyde (FA) is known to induce lung injury, but the underlying molecular mechanism remains largely unclear. CDR1as is an important member of the circular RNAs (circRNAs) family and functions as miRNA sponges with gene-regulatory potential. Our earlier circRNA microarray data showed CDR1as was highly expressed in lung tissue exposed to FA. However, the mechanism of circRNA-CDR1as mediates the FA-exposed lung injury is still unclear. This study aimed to explore the role of CDR1as in lung injury. MATERIALS AND METHODS: In this study, FA was inhaled at doses of 0.5, 2.46, and 5 mg/m3, respectively. After exposure 8 weeks, lung histopathological examination, lung injury score, and IL-1ß in bronchoalveolar lavage fluid (BALF) were determined. The expressions of CDR1as, rno-miR-7b and Atg7 were detected and the potential interaction of circRNA/miRNA/mRNA was predicted by bioinformatics analysis, including drawing circRNA/miRNA/mRNA interaction network, GO and KEGG analysis. RESULTS: Our results indicated FA inhalation upregulated the expression of CDR1as in lung tissues in a dose-dependent manner while the expression of rno-miR-7b decreased and Atg7 increased. Moreover, the alteration of CDR1as was positively correlated with lung injury. DISCUSSION AND CONCLUSIONS: CircRNA/miRNA/mRNA prediction further explained the possible effect mechanisms of CDR1as. These data implicated that CDR1as might be a critical regulator involved in lung injury induced by FA.

LncRNAs in tumor microenvironment: The potential target for cancer treatment with natural compounds and chemical drugs.

It was thought that originally long non-coding RNAs (lncRNAs) were a kind of RNAs without any encoding function. Recently, a variety of studies have shown that lncRNAs play important roles in many life activities. The abnormal expression of lncRNAs in tumor microenvironment (TME) usually promotes the proliferation, migration, and drug resistance of tumor cells through direct or indirect effects, which also usually predicts the poor prognosis. The regulation of lncRNAs expression in TME could significantly inhibit tumor progress. However, the interaction between lncRNAs and TME has not been fully defined at present. Therefore, this paper provided the systemic summary of their interaction and natural products and chemicals targeting lncRNAs in cancer treatment. Currently, the strategies of cancer treatment still have their limits. Understanding the relationship between TME and lncRNAs can help us to realize breakthrough strategy for tumor treatment.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

Natural products are an important source for proteasome regulating agents.

BACKGROUND: Natural medicines have a long history in the prevention and treatment of various diseases in East Asian region, especially in China. Modern research has proved that the pharmacological effects of numerous natural medicines involve the participation of ubiquitin proteasome system (UPS). UPS can degrade the unwanted and damaged proteins widely distributed in the nucleus and cytoplasm of various eukaryotes. PURPOSE: The objective of the present study was to review and discuss the regulatory effects of natural products and extracts on proteasome components, which may help to find new proteasome regulators for drug development and clinical applications. METHODS: The related information was compiled using the major scientific databases, such as CNKI, Elsevier, ScienceDirect, PubMed, SpringerLink, Wiley Online, and GeenMedical. The keywords "natural product" and "proteasome" were applied to extract the literature. Nature derived extracts, compounds and their derivatives involved in proteasome regulation were included, and the publications related to synthetic proteasome agents were excluded. RESULTS: The pharmacological effects of more than 80 natural products and extracts derived from phytomedicines related to the proteasome regulation were reviewed. These natural products were classified according to their chemical properties. We also summarized some laws of action of natural products as proteasome regulators in the treatment of diseases, and listed the action characteristics of the typical natural products. CONCLUSION: Natural products derived from nature can induce the degradation of damaged proteins through UPS or act as regulators to directly regulate the activity of proteasome. But few proteasome modulators are applied clinically. Summary of known rules for proteasome modulators will contribute to discover, modify and synthesize more proteasome modulators for clinical applications.