-
1.
Mitofilin in cardiovascular diseases: Insights into the pathogenesis and potential pharmacological interventions.
Chaurembo, AI, Xing, N, Chanda, F, Li, Y, Zhang, HJ, Fu, LD, Huang, JY, Xu, YJ, Deng, WH, Cui, HD, et al
Pharmacological research. 2024;:107164
Abstract
The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.
-
2.
Stereocontrolled access to thioisosteres of nucleoside di- and triphosphates.
Zhang, HJ, Ociepa, M, Nassir, M, Zheng, B, Lewicki, SA, Salmaso, V, Baburi, H, Nagel, J, Mirza, S, Bueschbell, B, et al
Nature chemistry. 2024;(2):249-258
Abstract
Nucleoside diphosphates and triphosphates impact nearly every aspect of biochemistry; however, the use of such compounds as tools or medicinal leads for nucleotide-dependent enzymes and receptors is hampered by their rapid in vivo metabolism. Although a successful strategy to address the instability of the monophosphate moiety in oligonucleotide therapeutics has been accomplished by their isosteric replacement with phosphorothioates, no practical methods exist to rapidly and controllably access stereopure di- and triphosphate thioisosteres of both natural and unnatural nucleosides. Here we show how a modular, reagent-based platform can enable the stereocontrolled and scalable synthesis of a library of such molecules. This operationally simple approach provides access to pure stereoisomers of nucleoside α-thiodiphosphates and α-thiotriphosphates, as well as symmetrical or unsymmetrical dinucleoside thiodiphosphates and thiotriphosphates (including RNA cap reagents). We demonstrate that ligand-receptor interactions can be dramatically influenced by P-stereochemistry, showing that such thioisosteric replacements can have profound effects on the potency and stability of lead candidates.
-
3.
[Post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation: a randomized controlled trial].
Cao, X, Zhang, HJ, Xu, G, Ma, XX, Pu, XL, Ma, WJ, Zhang, D, Tian, ZD, Zhang, WH
Zhongguo zhen jiu = Chinese acupuncture & moxibustion. 2023;(6):611-4
Abstract
OBJECTIVE To observe the clinical efficacy on post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation. METHODS Sixty patients with post-stroke dysphagia were randomly divided into an observation group and a control group, with 30 cases in each group. The neuromuscular electrical stimulation was adopted in the control group. Besides the treatment as the control group, in the observation group, the four-step acupuncture therapy for opening orifices and benefiting throat was supplemented. Step 1: the three areas of scalp acupuncture on the affected side were stimulated. Step 2: pricking method was operated on the posterior pharyngeal wall. Step 3: bleeding technique was operated at Jinjin (EX-HN 12) and Yuye (EX-HN 13). Step 4: deep insertion of needle was operated at three-pharynx points. The needles were retained for 30 min at the three areas of scalp acupuncture and the three-pharynx points. The intervention of each group was delivered once daily, 6 times a week, at the interval of 1 day. One course of treatment was 1 week and 4 successive courses were required. The rating of Kubota water swallow test, the score of standardized swallowing assessment (SSA) and the rating of Rosenbek penetration- aspiration scale (PAS) were observed before and after treatment in patients of the two groups. The incidence of clinical complications and clinical efficacy were compared between the two groups. RESULTS Compared with those before treatment, the rating of Kubota water swallow test, the scores of SSA and the rating of PAS of patients in the two groups were decreased after treatment (P<0.01), and the values of the observation group were lower than those of the control group after treatment (P<0.05). The incidence of clinical complications in the observation group was 13.3% (4/30), lower than 36.7% (11/30) in the control group (P<0.05). The total effective rate in the observation group was 93.3% (28/30), which was better than 70.0% (21/30) in the control group (P<0.05). CONCLUSION The four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation can improve the swallowing function of patients with post-stroke dysphagia and reduce the incidence of clinical complications.
-
4.
Lipid metabolism in malignant tumor brain metastasis: reprogramming and therapeutic potential.
Cheng, YJ, Fan, F, Zhang, Z, Zhang, HJ
Expert opinion on therapeutic targets. 2023;(9):861-878
Abstract
INTRODUCTION Brain metastasis is a highly traumatic event in the progression of malignant tumors, often symbolizing higher mortality. Metabolic alterations are hallmarks of cancer, and the mask of lipid metabolic program rearrangement in cancer progression is gradually being unraveled. AREAS COVERED In this work, we reviewed clinical and fundamental studies related to lipid expression and activity changes in brain metastases originating from lung, breast, and cutaneous melanomas, respectively. Novel roles of lipid metabolic reprogramming in the development of brain metastasis from malignant tumors were identified and its potential as a therapeutic target was evaluated. Published literature and clinical studies in databases consisting of PubMed, Embase, Scopus and www.ClinicalTrials.gov from 1990 to 2022 were searched. EXPERT OPINION Lipid metabolic reprogramming in brain metastasis is involved in de novo lipid synthesis within low lipid availability environments, regulation of lipid uptake and storage, metabolic interactions between brain tumors and the brain microenvironment, and membrane lipid remodeling, in addition to being a second messenger for signal transduction. Although some lipid metabolism modulators work efficiently in preclinical models, there is still a long way to go from laboratory to clinic. This area of research holds assurance for the organ-targeted treatment of brain metastases through drug-regulated metabolic targets and dietary interventions.
-
5.
Silica nanoparticle accumulation in plants: current state and future perspectives.
Pan, W, Zhang, HJ, Zhang, YF, Wang, M, Tsui, MT, Yang, L, Miao, AJ
Nanoscale. 2023;(37):15079-15091
Abstract
With their excellent biocompatibility, adjustable size, and high specific surface area, silica nanoparticles (SiO2 NPs) offer an alternative to traditional bulk fertilizers as a means to promote sustainable agriculture. SiO2 NPs have been shown to promote the growth of plants and to reduce the negative effects of biotic and abiotic stresses, but their bioaccumulation is a crucial factor that has been overlooked in studies of their biological effects. In this review, the techniques to quantify and visualize SiO2 NPs in plants were examined first. We then provide a summary of the current state of knowledge on the accumulation, translocation, and transformation of SiO2 NPs in plants and of the factors (e.g., the physicochemical properties of SiO2 NPs, plant species, application mode, and environmental conditions) that influence SiO2 NP bioaccumulation. The challenges in analyzing NP-plant interactions are considered as well. We conclude by identifying areas for further research that will advance our understanding of NP-plant interactions and thus contribute to more sustainable, eco-friendly, nano-enabled approaches to improving crop nutrient supplies. The information presented herein is important to improve the delivery efficiency of SiO2 NPs for precision and sustainable agriculture and to assess the safety of SiO2 NPs during their application in agriculture.
-
6.
The protective effects of sophocarpine on sepsis-induced cardiomyopathy.
Fu, Y, Zhang, HJ, Zhou, W, Lai, ZQ, Dong, YF
European journal of pharmacology. 2023;:175745
Abstract
This investigation elucidates the impact of sophocarpine treatment on lipopolysaccharide (LPS) stimulated sepsis-induced cardiomyopathy (SIC) via in vivo and in vitro experiments. Echocardiography, ELISA, TUNEL, Western blotting experiments, and Hematoxylin/Eosin, Dihydroethidium, and Immunohistochemistry staining assays, were carried out to identify associated indicators. The echocardiography revealed that sophocarpine treatment alleviated LPS-induced cardiac dysfunction as indicated by fractional shortening shortened and improved ejection fraction. Heart injury biomarkers, such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, were assessed, and indicated that sophocarpine treatment could alleviate LPS-induced upregulation of these indices. Furthermore, different experimental protocols revealed that sophocarpine treatment inhibits LPS-induced pathological alterations and decreases LPS-stimulated inflammatory cytokines, IL-1β, monocyte chemoattractant protein-1, IL-6, NOD-like receptor protein-3, and TNF-α, increase. Apoptotic proteins such as cytochrome-c, Bax, and cleaved-caspase-3 were increased, and Bcl-2 was alleviated after LPS stimulation; however, these effects were inhibited by sophocarpine treatment. Decreased antioxidant proteins [superoxide dismutase-1 (SOD-1) and SOD-2] induced by LPS stimulation were upregulated by sophocarpine treatment. LPS upregulated autophagic proteins such as Beclin-1 and the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I and downregulated sequestosome 1 (SQSTM1, or P62), sophocarpine therapy reversed these effects. Moreover, it was indicated that sophocarpine treatment inhibited the Toll-like receptor-4 (TLR-4)/nuclear transcription factor-kappa B (NF-κB) signaling pathway and activated nuclear factor erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In conclusion, sophocarpine treatment could alleviate LPS-trigger SIC by repressing oxidative stress, autophagy, inflammation, and apoptosis via TLR-4/NF-κB inhibition and Nrf2/HO-1 signaling pathway activation, implicating the potential of sophocarpine as a new therapeutic approach against SIC.
-
7.
Electrochemical corrosion protection of neat and zinc phosphate modified epoxy coating: A comparative physical aging study on Al alloy 6101.
Khan, AR, Zhang, HJ, Jun, Z, Maosheng, Z, Eldin, SM, Siddique, I
Frontiers in chemistry. 2023;:1142050
Abstract
Optimizing the pigment volume concentration of zinc phosphate pigments can protect Al alloy 6101 from alkaline media. Additionally, zinc phosphate pigments form a shielding film on the substrate and facilitate stopping the penetration of aggressive corrosion ions. The efficiency of eco-friendly zinc phosphate pigments is almost 98% during the corrosion analysis. A comparative study of physical aging of neat epoxy and Zinc Phosphate (ZP) pigment-modified epoxy coatings on Al alloy 6101 was conducted in Xi'an, China, for one year in all four seasons, where in summer for 3 months, results degraded more due to high UV radiation and humidity; it is found that peeling force of ZP pigments modified epoxy coatings is 50% higher of than that of the neat epoxy coatings though both peel-off adhesion strength and scratch test visibility decreased in both coatings; The electrochemical resistance of ZP pigments modified epoxy coatings is about 30% higher of than that of neat epoxy coatings, the corrosion rate of ZP pigments modified epoxy coatings is about 70% lower of than that of neat epoxy coatings, moreover the gloss retention is 20% higher in the modified epoxy; Optical surface observation of the coatings showed that the ZP modified epoxy coating could effectively restrict the crack and shrinkage in coatings after aging experimentation in the natural environment.
-
8.
Plant-derived lignans as potential antiviral agents: a systematic review.
Xu, XY, Wang, DY, Li, YP, Deyrup, ST, Zhang, HJ
Phytochemistry reviews : proceedings of the Phytochemical Society of Europe. 2022;(1):239-289
Abstract
Medicinal plants are one of the most important sources of antiviral agents and lead compounds. Lignans are a large class of natural compounds comprising two phenyl propane units. Many of them have demonstrated biological activities, and some of them have even been developed as therapeutic drugs. In this review, 630 lignans, including those obtained from medicinal plants and their chemical derivatives, were systematically reviewed for their antiviral activity and mechanism of action. The compounds discussed herein were published in articles between 1998 and 2020. The articles were identified using both database searches (e.g., Web of Science, Pub Med and Scifinder) using key words such as: antiviral activity, antiviral effects, lignans, HBV, HCV, HIV, HPV, HSV, JEV, SARS-CoV, RSV and influenza A virus, and directed searches of scholarly publisher's websites including ACS, Elsevier, Springer, Thieme, and Wiley. The compounds were classified on their structural characteristics as 1) arylnaphthalene lignans, 2) aryltetralin lignans, 3) dibenzylbutyrolactone lignans, 4) dibenzylbutane lignans, 5) tetrahydrofuranoid and tetrahydrofurofuranoid lignans, 6) benzofuran lignans, 7) neolignans, 8) dibenzocyclooctadiene lignans and homolignans, and 9) norlignans and other lignoids. Details on isolation and antiviral activities of the most active compounds within each class of lignan are discussed in detail, as are studies of synthetic lignans that provide structure-activity relationship information.
-
9.
Non-vitamin K oral anticoagulants versus vitamin K antagonists in post transcatheter aortic valve replacement patients with clinical indication for oral anticoagulation: A meta-analysis.
Chen, YF, Liu, F, Li, XW, Zhang, HJ, Liu, YG, Lin, L
Clinical cardiology. 2022;(4):401-406
Abstract
BACKGROUND Current guidelines recommend oral anticoagulation (OAC) following transcatheter aortic valve replacement (TAVR) in patients with clinical indication, but the optimal antithrombotic regimen remains uncertain. We aimed to compare the efficacy and safety of non-vitamin K oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in patients undergoing TAVR with concomitant indication of OAC. HYPOTHESIS Comparing with VKAs therapy, NOACs are similar in reducing the all-cause mortality and major bleeding in post-TAVR patients requiring OAC medication. METHODS We searched the databases of PubMed, Embase, and Cochrane library databases to identify studies that investigated NOACs versus VKAs after TAVR in patients with another indication of OAC, which were published before 28th September 28, 2021. The effectiveness of outcomes was all-cause mortality and stroke or systemic embolism, while the main safety outcome was major and/or life-threatening bleeding. The hazard ratio (HR) with 95% confidence interval (CI) was used as a measure of treatment effect. RESULTS Our search identified eight studies. We included 4947 post-TAVR patients with another indication of OAC allocated to the NOAC (n = 2146) or VKA groups (n = 2801). There were no significant differences in the all-cause mortality (HR: 0.91, 95% CI: 0.77-1.08, p = .29, I2 = 47%), stroke or systemic embolism (HR: 0.96, 95% CI: 0.68-1.37, p = .84, I2 = 0%), and major and/or life-threatening bleeding (HR: 1.09, 95% CI: 0.89-1.32, p = .40, I2 = 30%) in both groups. CONCLUSION Among post-TAVR patients who required OAC therapy, NOACs therapy compared to VKAs is similar in reducing the all-cause mortality, stroke or systemic embolism, and major and/or life-threatening bleeding events.
-
10.
Exploring the role of senescence inducers and senotherapeutics as targets for anticancer natural products.
Mamun, AA, Sufian, MA, Uddin, MS, Sumsuzzman, DM, Jeandet, P, Islam, MS, Zhang, HJ, Kong, AN, Sarwar, MS
European journal of pharmacology. 2022;:174991
Abstract
During the last few decades, cancer has remained one of the deadliest diseases that endanger human health, emphasizing urgent drug discovery. Cellular senescence has gained a great deal of attention in recent years because of its link to the development of cancer therapy. Senescent cells are incapable of proliferating due to irreversibly inhibition of the initiation of the cell cycle pathways. However, senescent cells aggregate in tissues and produce a pro-inflammatory secretome called senescence-associated secretory phenotype (SASP) that can cause serious harmful effects if not managed properly. There is mounting evidence that senescent cells lead to various phases of tumorigenesis in various anatomical sites, owing mostly to the paracrine activities of the SASP. Therefore, a new treatment field called senotherapeutics has been established. Senotherapeutics are newly developed anticancer agents that have been demonstrated to inhibit cancer efficiently. In light of recent findings, several promising natural products have been identified as senescence inducers and senotherapeutics, including, miliusanes, epigallocatechin gallate, phloretin, silybin, resveratrol, genistein, sulforaphane, quercetin, allicin, fisetin, piperlongumine, berberine, triptolide, tocotrienols and curcumin analogs. Some of them have already been validated through preclinical trials and exert an enormous potential for clinical trials. This review article focuses on and summarizes the latest advances made on cellular senescence and its potential as a target for cancer treatment and highlights the well-known natural products as senescence inducers and senotherapeutics for cancer treatment.