Background: Coronavirus disease 2019 (COVID-19) is posing a huge threat to human health worldwide. We aim to investigate the immune status of CD8 + T and NK cells in COVID-19 patients. Methods: The count and immune status of lymphocytes were detected by flow cytometry in 32 COVID-19 patients and 18 healthy individuals. Results: As the disease progression in COVID-19 patients, CD8 + T and NK cells were significantly decreased in absolute number but highly activated. After patients' condition improved, the count and immune status of CD8 + T and NK cells restored to some extent. GrA + CD8 + T and perforin + NK cells had good sensitivity and specificity for assisting diagnosis of COVID-19. Conclusions: As the disease progression, the declined lymphocytes in COVID-19 patients might lead to compensatory activation of CD8 + T and NK cells. GrA + CD8 + T and perforin + NK cells might be used as meaningful indicators for assisting diagnosis of COVID-19.
For the treatment of malignancy, many therapeutic agents, including small molecules, photosensitizers, immunomodulators, proteins and genes, and so forth, have been loaded into nanocarriers for controllable cancer therapy. Among these nanocarriers, polymeric micelles have been considered as one of the most promising nanocarriers, some of which have already been applied in different stages of clinical trials. The successful advantages of polymeric micelles from bench to bedside are due to their special core/shell structures, which can carry specific drugs in certain disease conditions. Particularly, poly(ethylene glycol)–polylactide (PEG–PLA) micelles have been considered as one of the most promising platforms for drug delivery. The PEG shell effectively prevents the adsorption of proteins and phagocytes, thereby evidently extending the blood circulation period. Meanwhile, the hydrophobic PLA core can effectively encapsulate many therapeutic agents. This review summarizes recent advances in PEG–PLA micelles for the treatment of malignancy. In addition, future perspectives for the development of PEG–PLA micelles as drug delivery systems are also presented.
Background Coronavirus disease 2019 (COVID-19) is affecting the whole world and threatening human health. We aim to investigate the immunological characteristics of monocytes in critical patients with COVID-19. Methods The number and immune status of monocytes were detected by flow cytometry in 32 COVID-19 patients and 18 healthy individuals. Results In critical patients with COVID-19, the absolute number of total monocytes and CD16 - monocytes was significantly decreased but CD16 + pro-inflammatory monocytes was increased compared to healthy controls. Antigen presentation potential of monocytes, as measured by HLA-DR expression, was suppressed, while their inflammatory phenotype (CD38 expression) was enhanced. Cytokine levels showed sustained increases in critical patients. And the levels of IL-6 were positively correlated with CD16 + monocytes number. IL-6 and IL-10 levels were negatively correlated with HLA-DR expression of monocytes. During the recovery of COVID-19 patients, the count and immune status of monocyte subsets were restored by degrees. HLA-DR + monocytes possessed good sensitivity and specificity for predicting the incidence of critical patients with COVID-19. Conclusions In critical patients with COVID-19, decline in number and HLA-DR expression of monocytes might lead to decreased antigen presentation potential and thus immunosuppression, while increased CD16 + pro-inflammatory monocytes might mediate hyperinflammation. HLA-DR + monocytes might be a meaningful assisted indicator to predict the incidence of critical patients with COVID-19.
We previously reported a critical role of reticulon (RTN) 1A in mediating endoplasmic reticulum (ER) stress in kidney tubular cells and the expression of RTN1A correlates with the renal function and the severity of kidney injury in patients with diabetic nephropathy (DN). Here, we determined the roles of RTN1A and ER stress in podocyte injury and DN. We used db/db mice with early unilateral nephrectomy (Unx) as a murine model of progressive DN and treated mice with tauroursodeoxycholic acid (TUDCA), a specific inhibitor of ER stress. We found increased expression of RTN1A and ER stress markers in the kidney of db/db-Unx mice. Treatment of TUDCA not only attenuated proteinuria and kidney histological changes, but also ameliorated podocyte and glomeruli injury in diabetic mice, which were associated with reduction of RTN1A and ER stress marker expression in the podocytes of TUDCA-treated mice. In vitro, we showed RTN1A mediates albumin-induced ER stress and apoptosis in human podocytes. A positive feedback loop between RTN1A and CHOP was found leading to an enhanced ER stress in podocytes. Our data suggest that ER stress plays a major role in podocyte injury in DN and RTN1A might be a key regulator of ER stress in podocytes.
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Current surgical treatments and material applications are not ideal for the treatment of orthopedic clinical injuries, such as large bone defects, cartilage defects, and vascular tendon adhesions that occur after repair. With the continuous development of tissue engineering technology, hydrogels have become important medical biomaterials. Hydrogels are three-dimensional hydrophilic network structures composed of cross-linked polymer chains. They are a new kind of polymeric material for the treatment of orthopedic diseases. Hydrogels have good biocompatibility, biodegradability, drug-carrying capacity, and controllable drug release ability and are less toxic than nanoparticle carriers. They have been widely used in wound repair, guided tissue regeneration, bacteriostasis, hemostasis, postoperative adhesion prevention, drug delivery, and 3D printing. These characteristics can be used to develop a variety of treatments for different diseases. This paper focuses on the innovative progress of hydrogels in promoting and improving bone, cartilage, tendon, and soft tissue regeneration in orthopedic clinical applications. Current and prospective applications of hydrogels in the field of orthopedics are discussed herein.
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