Prevention and treatment of inflammatory arthritis with traditional Chinese medicine: Underlying mechanisms based on cell and molecular targets

This comprehensive review examines the relationship between osteoarthritis (OA) and osteoporosis (OP), two common disorders in the elderly. OA involves joint cartilage degeneration and pain, while OP leads to fractures due to reduced bone mass. Despite different pathologies, both conditions share risk factors such as age and genetics. Studies reveal mixed results: some show higher bone mineral density (BMD) in OA patients, suggesting an inverse relationship, while others find no significant link. Proposed mechanisms include mechanical loading, bone remodeling, and inflammation. Clinical strategies focus on maintaining bone health in OA and monitoring joint health in OP, with treatments like bisphosphonates and exercise. Understanding these interactions is crucial for developing integrated treatments to improve patient outcomes and quality of life. Further research is needed to clarify these complex mechanisms. 

The interplay between osteoarthritis and osteoporosis: Mechanisms, implications, and treatment considerations – A narrative review

Stroke, as a neurological disorder with a poor overall prognosis, has long plagued the patients. Current stroke therapy lacks effective treatments. Ferroptosis has emerged as a prominent subject of discourse across various maladies in recent years. As an emerging therapeutic target, notwithstanding its initial identification in tumor cells associated with brain diseases, it has lately been recognized as a pivotal factor in the pathological progression of stroke. Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a potential target and biomarker of catalytic unsaturated fatty acids mediating ferroptosis in stroke. Specifically, the upregulation of ACSL4 leads to heightened accumulation of lipid peroxidation products and reactive oxygen species (ROS), thereby exacerbating the progression of ferroptosis in neuronal cells. ACSL4 is present in various tissues and involved in multiple pathways of ferroptosis. At present, the pharmacological mechanisms of targeting ACSL4 to inhibit ferroptosis have been found in many drugs, but the molecular mechanisms of targeting ACSL4 are still in the exploratory stage. This paper introduces the physiopathological mechanism of ACSL4 and the current status of the research involved in ferroptosis crosstalk and epigenetics, and summarizes the application status of ACSL4 in modern pharmacology research, and discusses the potential application value of ACSL4 in the field of stroke. 

The role of ACSL4 in stroke: mechanisms and potential therapeutic target

Abstract Astragalus glycyphyllos L. is widely used in Bulgarian folk medicine. Extracts from this plant have antiproliferative, antitumor and immune stimulating effects in vitro and in vivo. The aim of this study was to examine the potential antiviral activity of a standardized extract from the aerial parts of the plant and to formulate it in a suitable dosage form. A dry extract was obtained, and its phytochemical composition was determined by ultra-high-performance liquid chromatography–high resolution electrospray ionization mass spectrometry (UHPLC-HRESIMS). The extract contained flavonoids and predominantly saponins. 17(R),20(R)-3β,6α,16β-trihydroxycycloartanyl-23-carboxylic acid 16-lactone 3-O-β-D-glucopyranoside was used as a reference for quantitation. The extract had 3% saponins. The antiviral activity of the extract was tested against Simplexvirus humanalpha type 1 (acyclovir sensitive) and 2 (acyclovir resistant) in vitro. Between 60% and 70% of protection was reached against both virus strains when the extract (at the maximal non-toxic concentration of 0.6 mg/mL) was added simultaneously with and 1 h after Madine and Darby bovine kidney cell inoculation. The extract was also tested in combination with acyclovir only against Simplexvirus humanalpha type 1, in vitro. Further, the lyophilized extract was mixed with appropriate excipients aiming to prepare tablets via direct compaction. The optimized tablets fulfilled the requirements of the pharmacopoeia for disintegration and friability. Thus, the study demonstrated the possibility to formulate a standardized extract of A. glycyphyllos in tablets and their potential for adjuvant antiviral application in further trials.

Astragalus glycyphyllos L.: antiviral activity and tablet dosage formulation of a standardized dry extract

The ProTide prodrug design is a powerful tool to improve cell permeability and enhance the intracellular activation of nucleotide antiviral analogues. Previous in vitro studies showed that the activation of ProTide prodrugs varied in different cell lines. In the present study, we investigated the activation profiles of two antiviral prodrugs tenofovir alafenamide (TAF) and sofosbuvir (SOF) in five cell lines commonly used in antiviral research, namely, Vero E6, Huh-7, Calu-3, A549, and Caco-2. We found that TAF and SOF were activated in a cell-dependent manner with Vero E6 being the least efficient and Huh-7 being the most efficient cell line for activating the prodrugs. We also demonstrated that TAF was activated at a significantly higher rate than SOF. We further analyzed the protein expressions of the activating enzymes carboxylesterase 1, cathepsin A, histidine triad nucleotide-binding protein 1, and the relevant drug transporters P-glycoprotein and organic anion-transporting polypeptides 1B1 and 1B3 in the cell lines using the proteomics data extracted from the literature and proteome database. The results revealed significant differences in the expression patterns of the enzymes and transporters among the cell lines, which might partially contribute to the observed cell-dependent activation of TAF and SOF. These findings highlight the variability of the abundance of activating enzymes and transporters between cell lines and emphasize the importance of selecting appropriate cell lines for assessing the antiviral efficacy of nucleoside/nucleotide prodrugs. 

https://pubs.acs.org/doi/pdf/10.1021/acsptsci.3c00050

Cell-Dependent Activation of ProTide Prodrugs and Its Implications in Antiviral Studies

Astragaloside IV as a novel CXCR4 antagonist alleviates osteoarthritis in the knee of monosodium iodoacetate-induced rats.

Abstract With the deepening of green and sustainable development and the rapid development of the social economy, the modern logistics industry has also developed to an unprecedented level. In the logistics supply chain, due to the high value of the items inside the arrival carton, appearance inspection must be carried out before warehousing. However, manual inspection is slow and ineffective, resulting in the waste of manpower and packaging carton resources, which is not conducive to sustainable development. To address the above problems, this paper designs a logistics supply chain carton packaging quality defect detection system based on improved Single Shot MultiBox Detector (SSD) in the context of green sustainable development. The Implicit Feature Pyramid Network (IFPN) is introduced into SSD to improve the feature extraction ability of the model; the multiscale attention mechanism is introduced to collect more feature information. The experiment shows that the mAP and FPS of the system on the self-built data set reach 0.9662 and 36 respectively, which can realise the detection of the appearance defects of logistics cartons and help promote green sustainable development.

/pdf/ssd-based-carton-packaging-quality-defect-detection-system-t886j904.pdf

SSD-Based Carton Packaging Quality Defect Detection System for the Logistics Supply Chain

Cellular drug response (concentration required for obtaining 50% of a maximum cellular effect, EC50) can be predicted by the intracellular bioavailability (Fic) and biochemical activity (half-maximal inhibitory concentration, IC50) of drugs. In an ideal model, the cellular negative log of EC50 (pEC50) equals the sum of log Fic and the negative log of IC50 (pIC50). Here, we measured Fic’s of remdesivir, favipiravir, and hydroxychloroquine in various cells and calculated their anti-SARS-CoV-2 EC50’s. The predicted EC50’s are close to the observed EC50’s in vitro. When the lung concentrations of antiviral drugs are higher than the predicted EC50’s in alveolar type 2 cells, the antiviral drugs inhibit virus replication in vivo, and vice versa. Overall, our results indicate that both in vitro and in vivo antiviral activities of drugs can be predicted by their intracellular bioavailability and biochemical activity without using virus. This virus-free strategy can help medicinal chemists and pharmacologists to screen antivirals during early drug discovery, especially for researchers who are not able to work in the high-level biosafety lab.

Predicting In Vitro and In Vivo Anti-SARS-CoV-2 Activities of Antivirals by Intracellular Bioavailability and Biochemical Activity

Shang-Ke-Huang-Shui and coptisine alleviate osteoarthritis in the knee of monosodium iodoacetate-induced rats through inhibiting CXCR4 signaling.

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Papers

Astragaloside IV as a novel CXCR4 antagonist alleviates osteoarthritis in the knee of monosodium iodoacetate-induced rats.

SSD-Based Carton Packaging Quality Defect Detection System for the Logistics Supply Chain

Predicting In Vitro and In Vivo Anti-SARS-CoV-2 Activities of Antivirals by Intracellular Bioavailability and Biochemical Activity

Shang-Ke-Huang-Shui and coptisine alleviate osteoarthritis in the knee of monosodium iodoacetate-induced rats through inhibiting CXCR4 signaling.