PDZK1 protects against mechanical overload-induced chondrocyte senescence and osteoarthritis by targeting mitochondrial function.

Mechanical overloading and aging are two essential factors for osteoarthritis (OA) development. Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte biology, but their roles and the associated mechanisms in mechanical stress-associated chondrocyte senescence and OA have not been elucidated. Herein, we found that PDZ domain containing 1 (PDZK1), one of the PDZ proteins, which belongs to the Na+/H+ Exchanger (NHE) regulatory factor family, is a key factor in biomechanically induced mitochondrial dysfunction and chondrocyte senescence during OA progression. PDZK1 is reduced by mechanical overload, and is diminished in the articular cartilage of OA patients, aged mice and OA mice. Pdzk1 knockout in chondrocytes exacerbates mechanical overload-induced cartilage degeneration, whereas intraarticular injection of adeno-associated virus-expressing PDZK1 had a therapeutic effect. Moreover, PDZK1 loss impaired chondrocyte mitochondrial function with accumulated damaged mitochondria, decreased mitochondrion DNA (mtDNA) content and increased reactive oxygen species (ROS) production. PDZK1 supplementation or mitoubiquinone (MitoQ) application alleviated chondrocyte senescence and cartilage degeneration and significantly protected chondrocyte mitochondrial functions. MRNA sequencing in articular cartilage from Pdzk1 knockout mice and controls showed that PDZK1 deficiency in chondrocytes interfered with mitochondrial function through inhibiting Hmgcs2 by increasing its ubiquitination. Our results suggested that PDZK1 deficiency plays a crucial role in mediating excessive mechanical load-induced chondrocyte senescence and is associated with mitochondrial dysfunction. PDZK1 overexpression or preservation of mitochondrial functions by MitoQ might present a new therapeutic approach for mechanical overload-induced OA.

Physicochemical evaluation, structural characterization, in vitro and in vivo bioactivities of water-soluble polysaccharides from Luobuma (Apocynum L.) tea.

Luobuma tea is made from the leaves of Apocynum hendersonii (Bt) and A. venetum (Ht) and has been used for a very long time in China and Japan as herbal tea. This study isolated water-soluble polysaccharides from the two species` teas. Physicochemical properties, structural properties, in vitro and in vivo antioxidant and immunomodulatory activities were determined for the first time. The results showed that the Bt and Ht polysaccharides with molecular weights of 31.21 and 49.11 kDa, respectively, composed of arabinose, galactose, rhamnose, glucose, xylose, fucose, and mannose. A dose-dependent nitric oxide production and interleukin-6 inhibitory effects were obtained. Also, they suppressed the expression of cyclooxygenase-2, tumor necrosis factor-α and interleukin-6 mRNA in LPS-induced RAW 264.7 macrophages. Likewise, Bt and Ht have significantly reduced edema in the paws of mice after carrageenan injection. These results suggested that the Luobuma teas polysaccharides can be explored as potential antioxidants and anti-inflammatory agents.

G9a in Cancer: Mechanisms, Therapeutic Advancements, and Clinical Implications.

G9a, also named EHMT2, is a histone 3 lysine 9 (H3K9) methyltransferase responsible for catalyzing H3K9 mono- and dimethylation (H3K9me1 and H3K9me2). G9a contributes to various aspects of embryonic development and tissue differentiation through epigenetic regulation. Furthermore, the aberrant expression of G9a is frequently observed in various tumors, particularly in prostate cancer, where it contributes to cancer pathogenesis and progression. This review highlights the critical role of G9a in multiple cancer-related processes, such as epigenetic dysregulation, tumor suppressor gene silencing, cancer lineage plasticity, hypoxia adaption, and cancer progression. Despite the increased research on G9a in prostate cancer, there are still significant gaps, particularly in understanding its interactions within the tumor microenvironment and its broader epigenetic effects. Furthermore, this review discusses the recent advancements in G9a inhibitors, including the development of dual-target inhibitors that target G9a along with other epigenetic factors such as EZH2 and HDAC. It aims to bring together the existing knowledge, identify gaps in the current research, and suggest future directions for research and treatment strategies.

RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling.

Objectives: To investigate the potential role of Ribosomal protein L35 (RPL35) in regulating chondrocyte catabolic metabolism and to examine whether osteoarthritis (OA) progression can be delayed by overexpressing RPL35 in a mouse compression loading model. Methods: RNA sequencing analysis was performed on chondrocytes treated with or without 20 % elongation strain loading for 24 h. Experimental OA in mice was induced by destabilization of the medial meniscus and compression loading. Mice were randomly assigned to a sham group, an intra-articular adenovirus-mediated overexpression of the negative group, and an intra-articular adenovirus-mediated overexpression of the RPL35 operated group. The Osteoarthritis Research Society International score was used to evaluate cartilage degeneration. Immunostaining and western blot analyses were conducted to detect relative protein levels. Primary mouse chondrocytes were treated with 20 % elongation strain loading for 24 h to investigate the role of RPL35 in modulating chondrocyte catabolic metabolism and regulating cellular senescence in chondrocytes. Results: The protein expression of RPL35 in mouse chondrocytes was significantly reduced when excessive mechanical loading was applied, while elevated protein levels of RPL35 protected articular chondrocytes from degeneration. In addition, the RPL35 knockdown alone induced chondrocyte senescence, decreased the expression of anabolic markers, and increased the expression of catabolic markers in vitro in part through the hedgehog (Hh) pathway. Conclusions: These findings demonstrated a functional pathway important for OA development and identified intra-articular injection of RPL35 as a potential therapy for OA prevention and treatment. The translational potential of this article: It is necessary to develop new targeted drugs for OA due to the limitations of conventional pharmacotherapy. Our study explores and demonstrates the protective effect of RPL35 against excessive mechanical stress in OA models in vivo and in vitro in animals. These findings might provide novel insights into OA pathogenesis and show its translational potential for OA therapy.

Joint global and local interpretation method for CIN status classification in breast cancer.

Breast cancer is among the cancer types with the highest numbers of new cases. The study of this disease from a microscopic perspective has been a prominent research topic. Previous studies have shown that microRNAs (miRNAs) are closely linked to chromosomal instability (CIN). Correctly predicting CIN status from miRNAs can help to improve the survival of breast cancer patients. In this study, a joint global and local interpretation method called GL_XGBoost is proposed for predicting CIN status in breast cancer. GL_XGBoost integrates the eXtreme Gradient Boosting (XGBoost) and SHapley Additive exPlanation (SHAP) methods. XGBoost is used to predict CIN status from miRNA data, whereas SHAP is used to select miRNA features that have strong relationships with CIN. Furthermore, SHAP's rich visualization strategies enhance the interpretability of the entire model at the global and local levels. The performance of GL_XGBoost is validated on the TCGA-BRCA dataset, and it is shown to have an accuracy of 78.57% and an area under the curve value of 0.87. Rich visual analysis is used to explain the relationships between miRNAs and CIN status from different perspectives. Our study demonstrates an intuitive way of exploring the relationship between CIN and cancer from a microscopic perspective.

Clinically-observed FOXA1 mutations upregulate SEMA3C through transcriptional derepression in prostate cancer.

FOXA1 is a pioneer transcription factor that is frequently mutated in prostate, breast, bladder, and salivary gland malignancies. Indeed, metastatic castration-resistant prostate cancer (mCRPC) commonly harbour FOXA1 mutations with a prevalence of 35%. However, despite the frequent recurrence of FOXA1 mutations in prostate cancer, the mechanisms by which FOXA1 variants drive its oncogenic effects are still unclear. Semaphorin 3C (SEMA3C) is a secreted autocrine growth factor that drives growth and treatment resistance of prostate and other cancers and is known to be regulated by both AR and FOXA1. In the present study, we characterize FOXA1 alterations with respect to its regulation of SEMA3C. Our findings reveal that FOXA1 alterations lead to elevated levels of SEMA3C both in prostate cancer specimens and in vitro. We further show that FOXA1 negatively regulates SEMA3C via intronic cis elements, and that mutations in FOXA1 forkhead domain attenuate its inhibitory function in reporter assays, presumably by disrupting DNA binding of FOXA1. Our findings underscore the key role of FOXA1 in prostate cancer progression and treatment resistance by regulating SEMA3C expression and suggest that SEMA3C may be a driver of growth and tumor vulnerability of mCRPC harboring FOXA1 alterations.

Collaborative Transfer Network for Multi-Classification of Breast Cancer Histopathological Images.

The incidence of breast cancer is increasing rapidly around the world. Accurate classification of the breast cancer subtype from hematoxylin and eosin images is the key to improve the precision of treatment. However, the high consistency of disease subtypes and uneven distribution of cancer cells seriously affect the performance of multi-classification methods. Furthermore, it is difficult to apply existing classification methods to multiple datasets. In this article, we propose a collaborative transfer network (CTransNet) for multi-classification of breast cancer histopathological images. CTransNet consists of a transfer learning backbone branch, a residual collaborative branch, and a feature fusion module. The transfer learning branch adopts the pre-trained DenseNet structure to extract image features from ImageNet. The residual branch extracts target features from pathological images in a collaborative manner. The feature fusion strategy of optimizing these two branches is used to train and fine-tune CTransNet. Experiments show that CTransNet achieves 98.29% classification accuracy on the public BreaKHis breast cancer dataset, exceeding the performance of state-of-the-art methods. Visual analysis is carried out under the guidance of oncologists. Based on the training parameters of the BreaKHis dataset, CTransNet achieves superior performance on other two public breast cancer datasets (breast-cancer-grade-ICT and ICIAR2018_BACH_Challenge), indicating that CTransNet has good generalization performance.

MGGAN: A multi-generator generative adversarial network for breast cancer immunohistochemical image generation.

The immunohistochemical technique (IHC) is widely used for evaluating diagnostic markers, but it can be expensive to obtain IHC-stained section. Translating the cheap and easily available hematoxylin and eosin (HE) images into IHC images provides a solution to this challenge. In this paper, we propose a multi-generator generative adversarial network (MGGAN) that can generate high-quality IHC images based on the HE of breast cancer. Our MGGAN approach combines the low-frequency and high-frequency components of the HE image to improve the translation of breast cancer image details. We use the multi-generator to extract semantic information and a U-shaped architecture and patch-based discriminator to collect and optimize the low-frequency and high-frequency components of an image. We also include a cross-entropy loss as a regularization term in the loss function to ensure consistency between the synthesized image and the real image. Our experimental and visualization results demonstrate that our method outperforms other state-of-the-art image synthesis methods in terms of both quantitative and qualitative analysis. Our approach provides a cost-effective and efficient solution for obtaining high-quality IHC images.

Oriented Ultrathin π-complexation MOF Membrane for Ethylene/Ethane and Flue Gas Separations.

Rational design and engineering of high-performance molecular sieve membranes towards C2 H4 /C2 H6 and flue gas separations remain a grand challenge to date. In this study, through combining pore micro-environment engineering with meso-structure manipulation, highly c-oriented sub-100 nm-thick Cu@NH2 -MIL-125 membrane was successfully prepared. Coordinatively unsaturated Cu ions immobilized in the NH2 -MIL-125 framework enabled high-affinity π-complexation interactions with C2 H4 , resulting in an C2 H4 /C2 H6 selectivity approaching 13.6, which was 9.4 times higher than that of pristine NH2 -MIL-125 membrane; moreover, benefiting from π-complexation interactions between CO2 and Cu(I) sites, our membrane displayed superior CO2 /N2 selectivity of 43.2 with CO2 permeance of 696 GPU, which far surpassed the benchmark of other pure MOF membranes. The above multi-scale structure optimization strategy is anticipated to present opportunities for significantly enhancing the separation performance of diverse molecular sieve membranes.

Research on machine vision and deep learning based recognition of cotton seedling aphid infestation level.

Aphis gossypii Glover is a major insect pest in cotton production, which can cause yield reduction in severe cases. In this paper, we proposed the A. gossypii infestation monitoring method, which identifies the infestation level of A. gossypii at the cotton seedling stage, and can improve the efficiency of early warning and forecasting of A. gossypii, and achieve precise prevention and cure according to the predicted infestation level. We used smartphones to collect A. gossypii infestation images and compiled an infestation image data set. And then constructed, trained, and tested three different A. gossypii infestation recognition models based on Faster Region-based Convolutional Neural Network (R-CNN), You Only Look Once (YOLO)v5 and single-shot detector (SSD) models. The results showed that the YOLOv5 model had the highest mean average precision (mAP) value (95.7%) and frames per second (FPS) value (61.73) for the same conditions. In studying the influence of different image resolutions on the performance of the YOLOv5 model, we found that YOLOv5s performed better than YOLOv5x in terms of overall performance, with the best performance at an image resolution of 640×640 (mAP of 96.8%, FPS of 71.43). And the comparison with the latest YOLOv8s showed that the YOLOv5s performed better than the YOLOv8s. Finally, the trained model was deployed to the Android mobile, and the results showed that mobile-side detection was the best when the image resolution was 256×256, with an accuracy of 81.0% and FPS of 6.98. The real-time recognition system established in this study can provide technical support for infestation forecasting and precise prevention of A. gossypii.

Pathogenicity and innate immune responses induced by fowl adenovirus serotype 8b in specific pathogen-free chicken.

Fowl adenovirus serotype 8b (FAdV-8b), as causative agent of inclusion body hepatitis (IBH), poses a great threat to the poultry industry. Considering the importance of innate immune response in host against viral infections, we investigated pathogenicity of a FAdV-8b strain HLJ/151129 in 1-mo-old specific pathogen-free (SPF) chickens and immune responses of host to FAdV-8b infection in this study. The results demonstrated that no obvious clinical signs were observed in infected birds. Neither mobility nor mortality was observed in both FAdV-8b infected and control chickens, as well. However, hepatic necrosis and a small amount of inflammatory cell infiltration were observed by pathological analysis. Viral load was detected in bursa of Fabricius, cecal tonsils, liver, heart, spleen, Harderian glands, and thymus. Virus shedding and viremia generated as early as 3 days postinfection (dpi) (9/10) and reached the peak at 7 dpi (10/10). In addition, the infected birds had developed FAdV-specific antibodies at 7 dpi, and the antibody titers reached the peak at 14 dpi. Furthermore, the results demonstrated that the mRNA expression levels of most of toll-like receptors (TLRs), most of avian ß-defensins (AvBDs), and cytokines [interleukin (IL)-2, IL-6, and interferon (IFN)-γ], were significantly upregulated in most tissues at early phases of FAdV-8b infection, especially in liver and spleen. In contrast, FAdV-8b infection results in downregulation of TLR4, TLR5, and TLR21 expressions in some tissues of infected chickens. In addition, FAdV-8b infection upregulated myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB) p65, and TIR-domain-containing adapter inducing interferon-ß (TRIF) expression in some tissues, while decreased NF-κBp65 and TRIF in spleen at both 72 hpi and 21 dpi. Taken together, these results confirmed that FAdV-8b could replicate in all investigated tissues of infected birds, and then, result in production of FAdV-specific antibody titers. Meanwhile, the FAdV-8b infection induces strong innate immune responses at early stage in chickens, which may associate with the viral pathogenesis.

A correlation graph attention network for classifying chromosomal instabilities from histopathology whole-slide images.

The chromosome instability (CIN) is one of the hallmarks of cancer and is closely related to tumor metastasis. However, the sheer size and resolution of histopathology whole-slide images (WSIs) already challenges the capabilities of computational pathology. In this study, we propose a correlation graph attention network (MLP-GAT) that can construct graphs for classifying multi-type CINs from the WSIs of breast cancer. We construct a WSIs dataset of breast cancer from the Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA). Extensive experiments show that MLP-GAT far outperforms accepted state-of-the-art methods and demonstrate the advantages of the constructed graph networks for analyzing WSI data. The visualization shows the difference among the tiles in a WSI. Furthermore, the generalization performance of the proposed method was verified on the stomach cancer. This study provides guidance for studying the relationship between CIN and cancer from the perspective of image phenotype.

Phytochemical content and antioxidant activity of different anatomical parts of Corchorus olitorius and C. capsularis during different phenological stages.

Different parts of Corchorus olitorius and C. capsularis possess different antioxidant compounds. This study investigated the phytochemical components and antioxidant capacities of ultrasound-assisted extraction of different plant parts of both species using spectrophotometry at various phenological stages. Results also indicate that leaves, stems and roots of C. olitorius at various growth stages showed higher phytochemical components and antioxidant potential compared to C. capsularis. The phytochemical components from roots to leaves in C. olitorius including total polyphenol 0.97-11.11 mg GAE/g DW, total flavonoid 0.99-7.78 mg QE/g DW and total tannin 4.02-26.89 TA E/g DW, whereas C. capsularis total polyphenol 1.04-7.93 mg GAE/g DW, total flavonoid 0.77-5.5.92 mg QE/g DW and total tannin content 3.17-22.73 TA E/g DW. C. olitorius produced overall 22.23%, 13.61%, 12.24% higher total polyphenol, total flavonoid and total tannin, respectively compare to C. capsularis. Different parts extract also significantly affected antioxidant capacities including DPPH, ABTS, and FRAP activity with values of 22.03-79.46% inhibition, 10.84-104.10 µmol TE/g DW, and 10.84-104.10 µmol Fe2+/g DW respectively for C. olitorius, while C. capsularis demonstrated 14.03-70.97% of DPPH inhibition, 9.16-95.60 µmol TE/g DW of ABTS and 5.31-71.82 µmol Fe2+/g DW of FRAP activity. Moreover, leaves of the flowering stage, young stems and aged roots of both species displayed a higher content of phytochemical and antioxidant activities than other growth stages. A positive correlation between the phytochemical and antioxidant potential indicated that phenolic constituents solely affected antioxidant activity. Thus, this study established that the plant's parts and phenological growth stages significantly influence the concentration of phytoconstituents and antioxidant activities, and determine the harvesting stages of the different organs of C. olitorius and C. capsularis for considerable medicinal importance as folk and industry.

Down-regulated GAS6 impairs synovial macrophage efferocytosis and promotes obesity-associated osteoarthritis.

Obesity has always been considered a significant risk factor in osteoarthritis (OA) progression, but the underlying mechanism of obesity-related inflammation in OA synovitis remains unclear. The present study found that synovial macrophages infiltrated and polarized in the obesity microenvironment and identified the essential role of M1 macrophages in impaired macrophage efferocytosis using pathology analysis of obesity-associated OA. The present study revealed that obese OA patients and Apoe-/- mice showed a more pronounced synovitis and enhanced macrophage infiltration in synovial tissue, accompanied by dominant M1 macrophage polarization. Obese OA mice had a more severe cartilage destruction and increased levels of synovial apoptotic cells (ACs) than OA mice in the control group. Enhanced M1-polarized macrophages in obese synovium decreased growth arrest-specific 6 (GAS6) secretion, resulting in impaired macrophage efferocytosis in synovial ACs. Intracellular contents released by accumulated ACs further triggered an immune response and lead to a release of inflammatory factors, such as TNF-α, IL-1ß, and IL-6, which induce chondrocyte homeostasis dysfunction in obese OA patients. Intra-articular injection of GAS6 restored the phagocytic capacity of macrophages, reduced the accumulation of local ACs, and decreased the levels of TUNEL and Caspase-3 positive cells, preserving cartilage thickness and preventing the progression of obesity-associated OA. Therefore, targeting macrophage-associated efferocytosis or intra-articular injection of GAS6 is a potential therapeutic strategy for obesity-associated OA.

Effect and imaging analysis of cetuximab combined with radiotherapy in patients with rectal carcinoma.

OBJECTIVE: To analyze the effect of cetuximab combined with radiotherapy in patients with rectal carcinoma (RC) by imaging analysis. METHODS: The clinical data of 104 RC patients at our hospital from February 2021 to February 2022 were retrospectively analyzed. They were separated into control group (n = 52) and experimental group (n = 52) according to the order of admission, with the former treated with radiotherapy alone and the latter receiving cetuximab and radiotherapy. The clinical efficacy, tumor marker levels and imaging parameters of different treatment regimens were compared, and Quality of Life questionnaire (QLQ-C30) was used to evaluate the quality of life. RESULTS: The incidence of tumor regression grade (TRG) downgrade, T stage downgrade and N stage downgrade was remarkably higher in the experimental group than in the control group (P < 0.05). The experimental group had remarkably lower tumor marker levels (P < 0.001) and higher mean score of EORTC Core QLQ-C30 (P < 0.001) than those in the control group. The relative signal intensity of tumor (SIT/M), relative signal intensity reduction rate of tumor (SIT/MRR) and apparent diffusion coefficient (ADC) values were remarkably higher (P < 0.001) and the absolute signal intensity of tumor (SIT) value was remarkably lower (P < 0.001) in the experimental group than the control group. CONCLUSION: Treatment with cetuximab and radiotherapy can greatly reduce serum tumor marker levels in RC patients and bring them health benefits, and further studies will help establish a better solution for such patients.

SASG-GCN: Self-Attention Similarity Guided Graph Convolutional Network for Multi-Type Lower-Grade Glioma Classification.

Identifying the subtypes of low-grade glioma (LGG) can help prevent brain tumor progression and patient death. However, the complicated non-linear relationship and high dimensionality of 3D brain MRI limit the performance of machine learning methods. Therefore, it is important to develop a classification method that can overcome these limitations. This study proposes a self-attention similarity-guided graph convolutional network (SASG-GCN) that uses the constructed graphs to complete multi-classification (tumor-free (TF), WG, and TMG). In the pipeline of SASG-GCN, we use a convolutional deep belief network and a self-attention similarity-based method to construct the vertices and edges of the constructed graphs at 3D MRI level, respectively. The multi-classification experiment is performed in a two-layer GCN model. SASG-GCN is trained and evaluated on 402 3D MRI images which are produced from the TCGA-LGG dataset. Empirical tests demonstrate that SASG-GCN accurately classifies the subtypes of LGG. The accuracy of SASG-GCN achieves 93.62%, outperforming several other state-of-the-art classification methods. In-depth discussion and analysis reveal that the self-attention similarity-guided strategy improves the performance of SASG-GCN. The visualization revealed differences between different gliomas.

Nanostructured Conductive Polypyrrole for Antibacterial Components in Flexible Wearable Devices.

The power generated by flexible wearable devices (FWDs) is normally insufficient to eradicate bacteria, and many conventional antibacterial strategies are also not suitable for flexible and wearable applications because of the strict mechanical and electrical requirements. Here, polypyrrole (PPy), a conductive polymer with a high mass density, is used to form a nanostructured surface on FWDs for antibacterial purposes. The conductive films with PPy nanorods (PNRs) are found to sterilize 98.2 ± 1.6% of Staphylococcus aureus and 99.6 ± 0.2% of Escherichia coli upon mild electrification (1 V). Bacteria killing stems from membrane stress produced by the PNRs and membrane depolarization caused by electrical neutralization. Additionally, the PNR films exhibit excellent biosafety and electrical stability. The results represent pioneering work in fabricating antibacterial components for FWDs by comprehensively taking into consideration the required conductivity, mechanical properties, and biosafety.

Discovery of Novel Lin28 Inhibitors to Suppress Cancer Cell Stemness.

Lin28 is a pluripotency factor that regulates cancer cell stem-like phenotypes to promote cancer development and therapy-resistant tumor progression. It acts through its cold shock domain and zinc knuckle domain (ZKD) to interact with the Let-7 pre-microRNA and block Let-7 biosynthesis. Chemical inhibition of Lin28 from interacting with Let-7 presents a therapeutic strategy for cancer therapy. Herein, we present the computer-aided development of small molecules by in silico screening 18 million compounds from the ZINC20 library, followed by the biological validation of 163 predicted compounds to confirm 15 new Lin28 inhibitors. We report three lead compounds, Ln7, Ln15, and Ln115, that target the ZKD of both Lin28A and Lin28B isoforms and block Lin28 from binding Let-7. They restore Let-7 expression and suppress tumor oncogenes such as SOX2 in cancer cells and show strong inhibitory effects on cancer cell stem-like phenotypes. However, minimal impacts of these compounds were observed on Lin28-negative cells, confirming the on-target effects of these compounds. We conclude from this study the discovery of several new Lin28 inhibitors as promising candidate compounds that warrant further drug development into potential anticancer therapies.

A Comprehensive Review of C. capsularis and C. olitorius: A Source of Nutrition, Essential Phytoconstituents and Pharmacological Activities.

Plant bioactive compounds have gained global significance in terms of both medicinal and economic ramifications due to being easily accessible and are believed to be effective with fewer side effects. Growing relevant clinical and scientific evidence has become an important criterion for accepting traditional health claims of medicinal plants and also supports the traditional uses of Corchorus as folk medicine. C. capsularis and C. olitorius have broad applications ranging from textile to biocomposite, and young leaves and shoots are used as healthy vegetables and have long been used as traditional remedies for fever, ascites, algesia, liver disorders, piles, and tumors in many cultures. This review systematically summarized and emphasized the nutritional attributes, mostly available bioactive compounds, and biological and potential pharmaceutical properties of C. capsularis and C. olitorius, disclosed to users and non-users. Results suggest that various phytochemicals such as cardiac glycosides, phenols, flavonoids, sterols, lipids, and fatty acids were found or analytically identified in different plant parts (leaf, stem, seed, and root), and many of them are responsible for pharmacological properties and their antitumor, anticancer, antioxidant, antinociceptive, anti-inflammatory, analgesic, antipyretic, antiviral, antibacterial, anticonvulsant, antidiabetic and antiobesity, and cardiovascular properties help to prevent and cure many chronic diseases. In addition to their use in traditional food and medicine, their leaves have also been developed for skin care products, and some other possible uses are described. From this review, it is clear that the isolated compounds of both species have great potential to prevent and treat various diseases and be used as functional foods. In conclusion, this comprehensive review establishes a significant reference base for future research into various medical and functional food applications.

Pentraxin 3 regulated by miR-224-5p modulates macrophage reprogramming and exacerbates osteoarthritis associated synovitis by targeting CD32.

Emerging evidence has shown an imbalance in M1/M2 macrophage polarization to play an essential role in osteoarthritis (OA) progression. However, the underlying mechanistic basis for this polarization is unknown. RNA sequencing of OA M1-polarized macrophages found highly expressed levels of pentraxin 3 (PTX3), suggesting a role for PTX3 in OA occurrence and development. Herein, PTX3 was found to be increased in the synovium and articular cartilage of OA patients and OA mice. Intra-articular injection of PTX3 aggravated, while PTX3 neutralization reversed synovitis and cartilage degeneration. No metabolic disorder or proteoglycan loss were observed in cartilage explants when treated with PTX3 alone. However, cartilage explants exhibited an OA phenotype when treated with culture supernatants of macrophages stimulated with PTX3, suggesting that PTX3 did not have a direct effect on chondrocytes. Therefore, the OA anti-chondrogenic effects of PTX3 are primarily mediated through macrophages. Mechanistically, PTX3 was upregulated by miR-224-5p deficiency, which activated the p65/NF-κB pathway to promote M1 macrophage polarization by targeting CD32. CD32 was expressed by macrophages, that when stimulated with PTX3, secreted abundant pro-inflammation cytokines that induced severe articular cartilage damage. The paracrine interaction between macrophages and chondrocytes produced a feedback loop that enhanced synovitis and cartilage damage. The findings of this study identified a functional pathway important to OA development. Blockade of this pathway and PTX3 may prevent and treat OA.