Aims: High-Density Lipoprotein (HDL) is a complex structure unique to the human body. ApoA-1 protein is a significant structural/functional protein of HDL and provides a natural interaction with the SR-B1 receptors on the cell membrane. The overexpression of the SR-B1 receptor in the membrane of malignant cells suggests that targeting cancer cells can be possible using HDL. The objective of this study was to prepare HDL-conjugated chitosan nanoparticles containing a genetic material that can be used for liver cancer. Methods: HDL used in the preparation of the formulations have been obtained by isolating from blood samples taken from healthy volunteers. Bcl-2 siRNA inhibiting BCL-2 oncogene was selected as the genetic material. Chitosan nanoparticles were prepared using the ionic gelation method utilizing low molecular weight chitosan. Physicochemical properties of formulations, transfection efficacy, and cytotoxicity of them on 3T3 and HepG2 cell lines were examined. Results: The average diameters of the selected formulations were below 250 nm with a positive zeta potential value between +36 ± 0.1 and +34 ± 0.5 mV. All formulations protected Bcl-2 siRNA from enzymatic degradation in the presence of serum. Cellular uptake ratios of particles by HepG2 cells were found to be between 76% and 98%. HDL/chitosan nanoparticles/Bcl-2 siRNA complex was found to be more toxic when compared to chitosan nanoparticles/Bcl-2 siRNA complex and naked Bcl-2 siRNA. Conclusion: According to attained results, the HDL-conjugated chitosan nanoparticles can bring advantages for targeted siRNA delivery to malignant cells that overexpress SR-B1 receptors, such as HepG2.

Background: The improvements in the treatment of colorectal cancer (CRC) and prolongation of survival time have improved the incidence of bone metastasis. Forkhead box D3 (FOXD3) is involved in the development of CRC. However, the role and mechanism of FOXD3 in CRC bone metastases development are unknown. Objective: Using the combined bioinformatics and cytology experimental analyses, this study aimed to explore the mechanistic role of FOXD3 in the bone metastasis of colon cancer, thereby aiding in the treatment of colon cancer bone metastasis and identification of drug-targeting markers. Methods: First, the changes in the expression levels of the FOXD3 gene and differentially expressed genes (DEGs) between the colon cancer samples and colon cancer metastases were obtained from The Cancer Genome Atlas (TCGA) database. Then, the correlations of the FOXD3 gene with the DEGs were identified. Next, the effects of the FOXD3 on the proliferation and invasion abilities of colon cancer bone metastatic cells were identified using Cell Counting Kit-8 (CCK8) and Transwell cell migration assays, respectively. In addition, Western blot analysis was used to identify the expression levels of the proteins related to the EGFR/Ras/Raf/MEK/ERK(EGFR/ERK) signaling pathway and epithelial-to-mesenchymal transition (EMT). Results: FOXD3 was downregulated in colon cancer and could interact with multiple DEGs in colon cancer bone metastases. FOXD3 gene knockdown could increase the proliferation of human colon cancer bone metastatic cells and their invasive ability. FOXD3 gene knockdown could activate the expression of EGFR/ERK signaling pathway-related proteins and inhibit/promote the expression of EMT-related proteins, which in turn promoted the proliferation and metastasis of LoVo cells from colon cancer bone metastases. Conclusion: Overall, this study demonstrated that the downregulation of the FOXD3 gene might promote the proliferation of colon cancer bone metastatic cell lines through the EGFR/ERK pathway and promote their migration through EMT, thereby serving as a promising therapeutic target.

Aims: The study explains the production of useful liquid hydrocarbons by thermo-acidic catalytic thermal degradation of waste high-density polyethylene. A comparative study of the liquid samples with or without catalysts. Background: Energy demand is high in the world. Waste plastic conversion is nowadays a concern of interest research for scientists. HDPE (High-density polyethylene) is the most common plastic used in households. Different types of catalysts and techniques have been used in the alteration process of waste HDPE. This paper deals with the kandite group of catalyst kaolin and the montmorillonite group of catalyst sodium bentonite in acid-activated mutated form. Objective: This paper aims to explore the prominent utilization of kaolin clay and sodium bentonite clay minerals as a catalyst for the alteration of waste HDPE into fuel resources and to develop a cost-effective recycling experimental set-up for plastic waste conversion. Method: Thermo-catalytic acid activation has been done for clay mutation. Hydrochloric acid-activated catalysts have been used in this study. FT-IR (Fourier Transform Infrared Spectroscopy) and GC-MS (Gas Chromatography and Mass Spectrometer) techniques have been used to explore the prominent compounds in the product samples. Result: Maximum energy per photon for RO (Parent Oil/Raw Oil) and AO(Acid treated thermo-catalytic oil) samples are respectively 58034.01×1024 Joules and 59271.40×1024 Joules concerning wave numbers 2921.42 and 2983.71 cm-1. Compounds of functional groups C-CH3, CH2, alkenes, and CH3 have been identified for RO and AO samples. Less gaseous hydrocarbons 31.79% (outcomes) or 29.66 % (production yield) and 150.06 % of increment in wax have been calculated after using acid-treated catalysts. Aliphatic compounds like alkanes and alkenes are present in the samples. Conclusion: A mixture of acid-treated kaolin and acid-treated sodium bentonite as the catalysts for degrading waste HDPE into liquid oil greatly reduces wax formation. Average outcomes and production of liquid hydrocarbons are good results with the acid-treated catalytic degradation of HDPE waste. One remarkable fact is that the yield percentage of liquid products is higher in acid-activated catalytic thermal degradation.

Introduction: Cervical cancer is one of the malignant cancers with high mortality among women worldwide. Although vaccines and early detection have reduced cervical cancer mortality, it remains a malignancy with a high mortality rate in women. Objective: We aimed to develop a novel integrated strategy that combines metabolomics with network pharmacology to explore the therapeutic mechanisms of naringin in cervical cancer. The mechanism of naringin intervention in cervical cancer was initially clarified by metabolomics and network pharmacology. Methods: The method of LC-MS and network pharmacology for the detection and identification of potential biomarkers and the mechanisms of action of naringin was used. The metabolites were detected and identified based on ultra-high-performance liquid chromatography coupled with Quadrupole-Exactive Orbitrap MS (UHPLC-Q-Exactive Orbitrap MS) and followed by the network pharmacology analysis. Results: In network pharmacology, naringin played a synergetic role through regulatory shared pathways, such as steroid hormone biosynthesis, sphingolipid signaling pathway and arachidonic acid metabolism, etc. Besides, the metabolomics analysis showed that 20 differential metabolites and 10 metabolic pathways were mainly involved in the therapeutic effect of naringin on cervical cancer. The result showed that naringin treatment for cervical cancer mainly occurs through the following metabolic pathways: amino acid metabolism and arachidonic acid metabolism. Conclusion: This work provided valuable information and a scientific basis for further studies of naringin in the treatment of cervical cancer.

: Drug degradation is a process that can render pharmaceuticals inactive without causing any visible distortion. This can disrupt the therapeutic process, and on occasion, when the process produces toxic metabolites, it can have much more fatal consequences. Light is one of the most significant components that might cause deterioration, and several attempts have been made to improve and increase the practical photosensitizing of nano-scaled pharmaceuticals. Considering this, the insolubility and aggregating qualities of fullerenes have received significant attention. Fullerene is considered to have a unique carbon structure. In order to gain improved water solubility and biocompatible properties, fullerenes have been combined with water-soluble, biodegradable, and adjustable polymers. More specifically, these linkers exhibit increased tumor cell identification and greater tumor cell suppression when linked to therapeutic ligands (tumor-targeting) or stimuli-responsive polymers. According to scientific studies, fullerene-drug combinations can be used in certain complex diseases, like infectious and viral types. Several studies have combined fullerenes into nano-emulsions or liposomes for various pharmacological objectives. In the current work, fullerene/polymer nanomaterials are discussed for potential therapeutic techniques for the treatment of various diseases, particularly cancer and AIDS. According to the research studies, fullerene is a suitable element with outstanding physical and chemical properties that has a wide range of potential applications in the pharmaceutical industry, including drug delivery system design, photodynamic cancer therapy, and antioxidant therapy.

: Resveratrol is one of the most interesting naturally-occurring nonflavonoid phenolic compounds with various biological activities, such as anticancer, neuroprotection, antibacterial, and anti-inflammatory. However, there is no clinical usage of resveratrol due to either its poor activity or poor pharmacokinetic properties. Heteroarenes-modified resveratrol is one pathway to improve its biological activities and bioavailability, and form more modification sites. In this review, we present the progress of heteroaryl analogues of resveratrol with promising biological activities in the latest five years, ranging from the synthesis to the structure-activity relationship and mechanism of actions. Finally, introducing heteroarenes into resveratrol is an effective strategy, which focuses on the selectivity of structure-activity relationship in vivo.

Introduction: Zhilong Huoxue Tongyu capsule (ZLHX) is a traditional Chinese medicinal compound preparation, which exhibits obvious therapeutic effects on aspirin resistance (AR). However, the mechanism of ZLHX on AR is rarely reported. Objectives: This study aimed to explore the therapeutic effects of AR and the underlying mechanisms of ZLHX on AR rats. Methods: An AR model was established through treatment with a high-fat, high-sugar, and high-salt diet for 12 weeks and oral administration of aspirin (27 mg/kg/day) and ibuprofen (36 mg/kg/day) in weeks 9–12. The rats were administrated with ZLHX (225, 450, and 900 mg/kg) from week 12 to week 16. Blood samples were collected after the experiment. Thromboelastography analysis was performed, and the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined. Furthermore, the levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were determined with commercial ELISA kits. Finally, the gene expressions of microRNA-126-3p (miRNA-126-3p) and miRNA-34b-3p were detected through a real-time quantitative polymerase chain reaction. Results: Results demonstrated that ZLHX significantly inhibited platelet aggregation in the AR rats. Moreover, ZLHX markedly decreased the levels of TC, TG, and LDL-C and increased the level of HDL-C. Meanwhile, ELISA results confirmed that ZLHX can elevate the expression levels of TXB2 and 6-keto-PGF1α. Further studies suggested that ZLHX significantly downregulated the expression levels of miRNA-126-3p and miRNA-34b-3p. Conclusion: This study revealed that the therapeutic effect of ZLHX might be related to the regulation of lipid metabolism and the miRNA pathway.

Background: An endophytic fungal strain Penicillium crustosum was isolated from the seagrass Posidonia oceanica and investigated to identify its antimicrobial constituents and characterize its metabolome composition. The ethyl acetate extract of this fungus exhibited antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) as well as an anti-quorum sensing effect against Pseudomonas aeruginosa. Methods: The crude extract was profiled by UHPLC-HRMS/MS and the dereplication was assisted by feature-based molecular networking. As a result, more than twenty compounds were annotated in this fungus. To rapidly identify the active compounds, the enriched extract was fractionated by semi-preparative HPLC-UV applying a chromatographic gradient transfer and dry load sample introduction to maximise resolution. The collected fractions were profiled by 1H-NMR and UHPLC-HRMS. Results: The use of molecular networking-assisted UHPLC-HRMS/MS dereplication allowed preliminary identification of over 20 compounds present in the ethyl acetate extract of P. crustosum. The chromatographic approach significantly accelerated the isolation of the majority of compounds present in the active extract. The one-step fractionation allowed the isolation and identification of eight compounds (1-8). Conclusion: This study led to the unambiguous identification of eight known secondary metabolites as well as the determination of their antibacterial properties.

Background: The microplate benchtop brine shrimp test (BST) has been widely used for screening and bio-guided isolation of many active compounds, including natural products. Although the interpretation given to the results appears dissimilar, our findings suggest a correlation between positive results with a specific mechanism of action. Objective: This study aimed to evaluate drugs belonging to fifteen pharmacological categories having diverse mechanisms of action and carry out a bibliometric analysis of over 700 citations related to microwell BST. Methods: Test compounds were evaluated in a serial dilution on the microwell BST using healthy nauplii of Artemia salina and after 24 hrs of exposition, the number of alive and dead nauplii was determined, and the LC50 was estimated. A metric study regarding the citations of the BST miniaturized method, sorted by type of documents cited, contributing country, and interpretation of results was conducted on 706 selected citations found in Google Scholar. Results: Out of 206 drugs tested belonging to fifteen pharmacological categories, twenty-six showed LC50 values <100 µM, most of them belonging to the category of antineoplastic drugs; compounds with different therapeutical uses were found to be cytotoxic as well. A bibliometric analysis showed 706 documents citing the miniaturized BST; 78% of them belonged to academic laboratories from developing countries located on all continents, 63% interpreted their results as cytotoxic activity and 35% indicated general toxicity assessment. Conclusion: BST is a simple, affordable, benchtop assay, capable of detecting cytotoxic drugs with specific mechanisms of action, such as protein synthesis inhibition, antimitotic, DNA binding, topoisomerase I inhibitors, and caspases cascade interfering drugs. The microwell BST is a technique that is used worldwide for the bio-guided isolation of cytotoxic compounds from different sources.

Background: Ischemic stroke comprises 75% of all strokes and it is associated with a great frailty and casualty rate. Certain data suggest multiple long non-coding Ribonucleic Acids (lncRNAs) assist the transcriptional, post-transcriptional, and epi-genetic regulation of genes expressed in the CNS (Central Nervous System). However, these studies generally focus on differences in the expression patterns of lncRNAs and Messenger Ribonucleic Acids (mRNAs) in tissue samples before and after cere-bral ischemic injury, ignoring the effects of age. Methods: In this study, differentially expressed lncRNA analysis was performed based on RNA-seq data from the transcriptomic analysis of murine brain microglia related to cerebral ischemia injury in mice at different ages (10 weeks and 18 months). Results: The results showed that the number of downregulate differentially ex-pressed genes (DEGs) in aged mice was 37 less than in young mice. Among them, lncRNA Gm-15987, RP24-80F7.5, XLOC_379730, XLOC_379726 were significant-ly down-regulated. Then, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these specific lncRNAs were mainly related to inflammation. Based on the lncRNA/mRNA co-expression network, the mRNA co-expressed with lncRNA was mainly enriched in pathways, such as im-mune system progression, immune response, cell adhesion, B cell activation, and T cell differentiation. Our results indicate that the downregulation of lncRNA, such as Gm-15987, RP24-80F7.5, XLOC_379730, and XLOC_379726 in aged mice may attenuate microglial-induced inflammation via the progress of immune system progression im-mune response, cell adhesion, B cell activation, and T cell differentiation. Conclusion: The reported lncRNAs and their target mRNA during this pathology have potentially key regulatory functions in the cerebral ischemia in aged mice while being important for diagnosing and treating cerebral ischemia in the elderly.

Background: Fuzi-Gancao herb couple is one of the most common herb couples involved in the TCM formula, which was used for the treatment of chronic diseases. The herb couple has a hepatoprotective effect. However, its main components and therapeutic mechanism are not yet clear. This study aims to elucidate the therapeutic effect and mechanism of the Fuzi-Gancao herb couple on NAFLD from animal experiments, network pharmacology, and molecular docking. Methods: 60 Male C57BL/6 mice (20 g ± 2 g) were randomly divided into six groups including the blank group (n=10) and NALFD group (n=50). The mice of the NALFD group were fed with a high-fat diet for 20 weeks to establish the NAFLD model and the NALFD mice were randomly divided into five groups including positive group (berberine), model group and F-G groups with three dosages (0.257, 0.514, 0.771 g/kg) (n=10). After 10 weeks of administration, the serum was collected for the analysis of ALT, AST, LDL-c, HDL-c, and TC, and liver tissues were collected for pathological analysis. The TCMAS database was used to collect the main components and targets of the Fuzi-Gancao herb couple. The GeneCards database was used to collect NAFLD-related targets, and the key targets were obtained by intersecting with herbal targets. The disease-component-target relationship diagram was constructed by Cytoscape 3.9.1. The obtained key targets were imported into the String database to obtain the PPI network, and imported into the DAVID database for KEGG pathway analysis and GO analysis. Finally, the key targets and key gene proteins were imported into Discovery Studio 2019 for molecular docking verification. Results: In this study, H-E staining indicated the pathological changes of liver tissue in Fuzi-Gancao groups were significantly improved, and the levels of AST, ALT, TC, HDL-c, and LDL-c in serum of Fuzi-Gancao groups decreased in a dose-dependent manner, compared with the model group. 103 active components and 299 targets in the Fuzi-Gancao herb couple were confirmed in the TCMSP database and 2062 disease targets in NAFLD were obtained. 142 key targets and 167 signal pathways were screened, such as the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and so on. The main bioactive ingredients of Fuzi-Gancao herb couple in the treatment of NAFLD are quercetin, kaempferol, naringenin, inermine, (R)-norcoclaurine, isorhamnetin, ignavine, 2,7-Dideacetyl-2,7-dibenzoyl-taxayunnanine F, glycyrol mainly involving IL6, AKT1, TNF, TP53, IL1B, VEGFA and other core targets. Molecular docking analysis indicated that there is a good affinity between the key components and the key targets. Conclusion: This study preliminarily explained the main components and mechanism of the Fuzi-Gancao herb couple in the treatment of NAFLD and provided an idea for subsequent research.

Background: Melanoma is the deadliest form of skin cancer. Heat shock protein 90 (Hsp90) is highly expressed in human melanoma. Hsp90 inhibitors can suppress the growth of human melanoma A375 cells; however, the underlying mechanism remains unclear. Methods: A375 cells were treated with SNX-2112, an Hsp90 inhibitor, for 48 h, and whole-transcriptome sequencing was performed. Results: A total of 2,528 differentially expressed genes were identified, including 895 upregulated and 1,633 downregulated genes. Pathway enrichment analyses of differentially expressed mRNAs identified the extracellular matrix (ECM)-receptor interaction pathway as the most significantly enriched pathway. The ECM receptor family mainly comprises integrins (ITGs) and collagens (COLs), wherein ITGs function as the major cell receptors for COLs. 19 upregulated miRNAs were found to interact with 6 downregulated ITG genes and 8 upregulated miRNAs were found to interact with 3 downregulated COL genes. 9 differentially expressed circRNAs in SNX-2112-treated A375 cells were identified as targets of the ITG- and COL-related miRNAs. Based on the differentially expressed circRNAs, miRNAs, and mRNAs, ITGs- and COL-based circRNA-miRNA-mRNA regulatory networks were mapped, revealing a novel regulatory mechanism of Hsp90-regulated melanoma. Conclusion: Targeting the ITG-COL network is a promising approach to the treatment of melanoma.

Aim: This study aimed to investigate how ω-9 MUFAs in fat emulsion affect serum IL-6 levels in rats with lipopolysaccharide (LPS)-induced lung injury. Background: Research suggests that acute lung injury (ALI) develops acute respiratory distress syndrome (ARDS) due to the activation of many inflammatory factors. ALI may be treated by reducing inflammation. Fat emulsion is used in parenteral nutrition for critically ill patients to regulate the body's inflammatory response. It is mostly made up of ω-9 MUFAs (Clinoleic), which can regulate the inflammatory response. Objective: The effect of ω-9MUFAs on the secretion of IL-6 in ALI rats was studied in order to provide a basis for the rational use of fat emulsion in clinical practice and provide new ideas for the diagnosis and treatment of ALI. Methods: The control, model, and -9MUFAs groups consisted of 18 female Sprageue-Dawley (SD) young rats (180 ± 20 g). The SD young rats received normal saline and were not operated. LPS-induced ALI animals received tail vein injections of normal saline. SD young rats were first triggered with acute lung injury by LPS (3 mg/kg) and then injected with 3 mg/kg of ω-9MUFAs via the tail vein. The expression levels of IL-6, an activator of signal transduction transcription 3 (STAT3), transforming growth factor-β (TGF-β), and glycoprotein 130 (GP130) in serum and lung tissues were determined by ELISA and Western blot methods. Results: Compared with the model group, the survival rate of rats in the ω-9 MUFAs group was significantly increased, and the difference was statistically significant (p<0.05). Compared with the model group, the lung pathology of rats in the ω-9 MUFAs group was significantly improved, and the expression levels of IL-6, TGF-β1, GP130, IL-1 and other proteins were significantly decreased. The difference was statistically significant (p<0.05). Conclusion: In LPS-induced lung injury, ω-9MUFAs may alleviate symptoms by inhibiting the IL-6/GP130/STAT3 pathway.

Background: Evidence of type 2 diabetes mellitus (T2DM) associated with hippocampal atrophy is reported by researchers all around the globe. The majority of such studies were conducted among the geriatric and elderly populations with other substantial co-morbid diseases. Hence, the present study aims to evaluate the hippocampal volume of T2DM subjects below 60 years without any concomitant disorders and assess the declarative memory. Materials and Methods: The cross-sectional observational study was conducted among the ethnic population of Manipur. A total of 17 T2DM subjects and 17 healthy controls, who are apparently healthy, matched by age, sex, and comparable education, were enrolled in the study. Magnetic Resonance Imaging (MRI) of high-resolution sagittal structural T1-weighted anatomical sequence was acquired using a three-dimension magnetization-prepared rapid-acquisition gradient echo (MPRAGE). The hippocampus volume was measured using the volBrain Automated MRI Brain Volumetry System. Declarative memory was estimated by the Rey Auditory Verbal Learning Test (RAVLT). Results: No statistically significant differences were found in hippocampal volume, and RAVLT scores between T2DM subjects, and healthy controls group (P > 0.05). Conclusions: The study data indicates that there is no particular hippocampal volume vulnerability in T2DM participants within the ethnic population of Manipur.

Background: Osteosarcoma is a disease that primarily affects adolescents with skeletal immaturity. LncRNAs are abnormally expressed and correlated with osteosarcoma patients' prognosis. We identified aberrant expression of LncRNA SNHG25 (small nucleolar RNA host gene 25) in osteosarcoma and analyzed the molecular mechanisms by which it regulates osteosarcoma progression. Methods: The expression levels of SNHG25 in tumour specimens and cells were measured by RT-qPCR. Loss-of-function assays were conducted to investigate the functional role of SNHG25 in vitro and in vivo. Bioinformatic predictions, dual-luciferase reporter assays, and western blotting were performed to explore the possible underlying mechanisms. Results: SNHG25 was highly expressed in osteosarcoma cells and tissues. The Kaplan–Meier curve showed that the survival rate of patients with high SNHG25 expression was significantly lower than those with low SNHG25 expression. Functional studies have indicated that inhibition of SNHG25 suppresses cell proliferation, migration, and invasion, while promoting apoptosis. SNHG25 knockdown suppresses osteosarcoma tumour growth in vivo. SNHG25 functions as a sponge for miR-497-5p in osteosarcoma cells. The level of SNHG25 was negatively correlated with that of miR-497-5p. The proliferation, invasion, and migration of osteosarcoma cells were restored by transfection of the miR-497-5p inhibitor in the SNHG25 knockdown group. Conclusion: SNHG25 was determined to function as an oncogene by promoting osteosarcoma cell proliferation, invasion, and migration through the miR-497-5p/SOX4 axis. Upregulation of SNHG25 expression indicated poor prognosis in patients with osteosarcoma, which showed that SNHG25 may serve as a potential therapeutic target and prognostic biomarker in osteosarcoma.

Background: Doxorubicin-induced heart failure is a clinical problem that needs to be solved urgently. Previous studies have confirmed that Zhenwu Decoction, a traditional Chinese medicine compound, can effectively improve chronic heart failure. However, its interventional effect on Doxorubicin-induced heart failure has not yet been investigated. In this study, we investigated the therapeutic effect and potential mechanism of Zhenwu Decoction on Doxorubicininduced heart failure through animal experiments and network pharmacology. Objective: The study aimed to investigate the therapeutic effect and potential mechanism of Zhenwu Decoction (ZWD) on Doxorubicin-induced heart failure. Methods: A heart-failure mouse model was established in 8-week-old male C57/BL6J mice using Doxorubicin, and the mice were then treated with ZWD for a 4-week period. Firstly, network pharmacology was conducted to explore the potential active components and molecular mechanisms of ZWD on Doxorubicin-induced heart failure. Next, we conducted an in vivo study on the effect of ZWD on Doxorubicin-induced heart failure. After the intervention, the cardiac function and levels of cardiac function injury marker in serum were measured to evaluate the therapeutic effect of ZWD on cardiac function. Then HE staining and Masson staining were used to evaluate the effect of ZWD on myocardial pathology, and biochemical method was used to detect the effect of ZWD on total antioxidant capacity and inflammation, and finally, Western blot was used to detect TGFβ, Smad-3, and collagen I protein expression levels to evaluate its effect on myocardial fibrosis. Results: In Doxorubicin-induced heart failure mice, ZWD improved cardiac function and reduced the levels of CK-MB, NT-proBNP, and BNP in the serum, improved myocardial pathology, and reduced TGFβ, Smad-3 and collagen I protein expression levels to improve myocardial fibrosis. Network pharmacological analysis showed that ZWD has 146 active ingredients and 248 candidate targets. Moreover, 2,809 genes were found to be related to Doxorubicin-induced heart failure, and after screening, 74 common targets were obtained, mainly including IL-6, AKT1, caspase-3, PPARG, PTGS2, JUN, HSP90AA1, and ESR1. KEGG analysis confirmed that PI3K/AKT and IL- 6/NF-κB signaling pathways were the two main pathways underlying the cardioprotective effects of ZWD. Finally, in vivo experiments showed that ZWD improved the total antioxidant capacity, reduced the SOD level, increased the protein expression of PI3K, Akt, Bcl-2, Bax, and caspase-3, reduced the levels of TNF-α, IL-6, and IL-1β, and decreased the NF-κB p65, IL-6, and TNF-α protein expression levels. Conclusion: In Doxorubicin-induced heart-failure mice, Zhenwu Decoction improved the cardiac function and myocardial pathology, and improved myocardial fibrosis through the TGFβ/Smad-3 signaling pathway. According to the prediction of network pharmacology, in vivo experiments demonstrated that Zhenwu Decoction can improve the oxidative stress response, improve myocardial cell apoptosis through the PI3K/AKT signaling pathway, and improve myocardial inflammation by reducing the levels of inflammatory factors and by reducing the protein expression of NF- κB p65, IL-6, and TNF-α.

Background: A series of novel oligomers with various types and complex skeletons are isolated from Annonaceae plants, which displayed anti-inflammatory, antimalarial, antibacterial and other biological activities. Thus, their structures and functions have received more and more attention. Aim and Objective: The purpose of this review is to provide a systematic reference for chemical structures and biological activities of oligomers and some clues for finding more analogues from Annonaceae. Methods: Publications relevant to Annonaceae were retrieved from the Web of Science and SciFinder and surveyed for a literature review. Results: This article summarized the chemical structures, the base source plants and the biofunctions of oligomers from Annonaceae. Conclusion: The oligomers from Annonaceae have the characteristics of various connection modes and rich functional groups, which provides more possibilities for the discovery of lead compounds with new or higher biological activities.

Background: Diabetic nephropathy (DN) is a major complication of diabetes. Schisandrin B (Sch) is a natural pharmaceutical monomer that was shown to prevent kidney damage caused by diabetes and restore its function. However, there is still a lack of comprehensive and systematic understanding of the mechanism of Sch treatment in DN. Objective: We aim to provide a systematic overview of the mechanisms of Sch in multiple pathways to treat DN in rats. Methods: Streptozocin was used to build a DN rat model, which was further treated with Sch. The possible mechanism of Sch protective effects against DN was predicted using network pharmacology and was verified by quantitative proteomics analysis. Results: High dose Sch treatment significantly downregulated fasting blood glucose, creatinine, blood urea nitrogen, and urinary protein levels and reduced collagen deposition in the glomeruli and tubule-interstitium of DN rats. The activities of superoxide dismutase (SOD) and plasma glutathione peroxidase (GSH-Px) in the kidney of DN rats significantly increased with Sch treatment. In addition, the levels of IL-6, IL-1β, and TNF-α were significantly reduced in DN rats treated with Sch. 11 proteins that target both Sch and DN were enriched in pathways such as MAPK signaling, PI3K-Akt signaling, renal cell carcinoma, gap junction, endocrine resistance, and TNF signaling. Furthermore, quantitative proteomics showed that Xaf1 was downregulated in the model vs. control group and upregulated in the Sch-treated vs. model group. Five proteins, Crb3, Tspan4, Wdr45, Zfp512, and Tmigd1, were found to be upregulated in the model vs. control group and downregulated in the Sch vs. model group. Three intersected proteins between the network pharmacology prediction and proteomics results, Crb3, Xaf1, and Tspan4, were identified. Conclusion: Sch functions by relieving oxidative stress and the inflammatory response by regulating Crb3, Xaf1, and Tspan4 protein expression levels to treat DN disease.

Background: Liver cirrhosis is one of the leading causes of decreased life expectancy worldwide. However, the molecular mechanisms underlying liver cirrhosis remain unclear. In this study, we performed a comprehensive analysis using transcriptome and metabolome sequencing to explore the genes, pathways, and interactions associated with liver cirrhosis. Methods: We performed transcriptome and metabolome sequencing of blood samples from patients with cirrhosis and healthy controls (1:1 matched for sex and age). We validated the differentially expressed microRNA (miRNA) and mRNAs using real-time quantitative polymerase chain reaction. Results: For transcriptome analysis, we screened for differentially expressed miRNAs and mRNAs, analyzed mRNAs to identify possible core genes and pathways, and performed co-analysis of miRNA and mRNA sequencing results. In terms of the metabolome, we screened five pathways that were substantially enriched in the differential metabolites. Next, we identified the metabolites with the most pronounced differences among these five metabolic pathways. We performed receiver operating characteristic (ROC) curve analysis of these five metabolites to determine their diagnostic efficacy for cirrhosis. Finally, we explored possible links between the transcriptome and metabolome. Conclusion: Based on sequencing and bioinformatics, we identified miRNAs and genes that were differentially expressed in the blood of patients with liver cirrhosis. By exploring pathways and disease-specific networks, we identified unique biological mechanisms. In terms of metabolomes, we identified novel biomarkers and explored their diagnostic efficacy. We identified possible common pathways in the transcriptome and metabolome that could serve as candidates for further studies.

Background: Whole exome sequencing (WES) provides support for clinical diagnosis and treatment of genetically related diseases based on specific probe capture and high-throughput second-generation sequencing technology. Familial partial lipodystrophy 2 (FPLD2; OMIM # 151660) or type 2 Köbberling-Dunnigan syndrome with insulin resistance syndrome is uncommon in mainland China and elsewhere. Aims: We report the case in order to have a further understanding of FPLD2 or type 2 KobberlingDunnigan syndrome) with the assistance of WES and improve the clinical and genetic understanding and diagnosis of this disease. Case: A 30-year-old woman was admitted to the cadre department of our hospital at 14:00 on July 11, 2021, because of hyperglycemia, a rapid heart rate, and excessive sweating during pregnancy. An oral glucose tolerance test (OGTT) showed that insulin and C-peptide increased slowly after glucose stimulation, and the peak value was extended backward (Table 1). It was suggested that the patient had developed insulin antibodies, resulting in insulin resistance. Her clinical features and familial inheritance were consistent with FPLD2 (type 2 Kobberling-Dunnigan syndrome). The results of WES indicated that a heterozygous mutation occurred in exon 8 of the LMNA gene, because the base C at position 1444 was mutated into T during transcription. This mutation changed the amino acid position 482 of the encoded protein from Arg to Trp. Type 2 KobberlingDunnigan syndrome is associated with an LMNA gene mutation. According to the patient's clinical manifestations, hypoglycemic and lipid-lowering therapy is recommended. Conclusion: WES can assist in the simultaneous clinical investigation or confirmation of FPLD2 and help identify diseases with similar clinical phenotypes. This case demonstrates that familial partial lipodystrophy is associated with an LMNA gene mutation on chromosome 1q21-22. This is one of the few cases of familial partial lipodystrophy diagnosed by WES.