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It is a challenge to carry G2/M-phase specific antitumor drugs into G2/M phase of cancer cells. For this purpose, we set up a pH-sensitive mixed micellar system based on poly(ethylene glycol)-b-poly( l -histidine) (PEG-PHIS) and poly(ethylene glycol)-b-poly(D, l -lactide) (PEG-PDLLA), and we used duramycin, a highly specific phosphatidylethanolamine-binding peptide, as a G2/M-phase specific targeting ligand to modify PEG-PDLLA. The mixed micelles were characterized by dynamic light scattering, electron microscopy and the pyrene fluorescence probe method. The G2/M-phase specific anti-cancer drug paclitaxel was loaded with a size of 189 ± 5 nm. And the drug-loading content and encapsulation efficiency were 14.7 ± 0.3% and 89.1 ± 2.5%, respectively. In addition, cytotoxicity assay showed that paclitaxel-loaded mixed micelles had effective antitumor effects, and the blank mixed micelles were safe. Importantly, the micelles showed pH sensitivity and G2/M-phase specific uptake. What's more, pharmacokinetic and in vivo imaging study showed that the mixed micelles displayed a prolonged circulation time and improved targeted accumulation at tumor sites. All these results suggest that the mixed micelle was a promising G2/M-phase specific drug delivery system.

As the threat of COVID-19 increases, many countries have carried out various non-pharmaceutical interventions. Although many studies have evaluated the impact of these interventions, there is a lack of mapping between model parameters and actual geographic areas. In this study, a non-pharmaceutical intervention model of COVID-19 based on a discrete grid is proposed from the perspective of geography. This model can provide more direct and effective information for the formulation of prevention and control policies. First, a multi-level grid was introduced to divide the geographical space, and the properties of the grid boundary were used to describe the quarantine status and intensity in these different spaces, this was also combined with the model of hospital isolation and self-protection. Then, a process for the spatiotemporal evolution of the early COVID-19 spread is proposed that integrated the characteristics of residents’ daily activities. Finally, the effect of the interventions was quantitatively analyzed by the dynamic transmission model of COVID-19. The results showed that quarantining is the most effective intervention, especially for infectious diseases with a high infectivity. The introduction of a quarantine could effectively reduce the number of infected humans, advance the peak of the maximum infected number of people, and shorten the duration of the pandemic. However, quarantines only function properly when employed at sufficient intensity, hospital isolation and self-protection measures can effectively slow the spread of COVID-19, thus providing more time for the relevant departments to prepare, but an outbreak will occur again when the hospital reaches full capacity. Moreover, medical resources should be concentrated in places where there is the most urgent need under a strict quarantine measure.

Idiopathic membranous nephropathy (IMN) is an autoimmune disease in which the immune system produces an antibody response to its own antigens due to impaired immune tolerance. Although antibodies are derived from plasma cells differentiated by B cells, the T-B cells also contribute a lot to the immune system. In particular, the subsets of helper T (Th) cells, including the dominant subsets such as Th2, Th17, and follicular helper T (Tfh) cells and the inferior subsets such as regulatory T (Treg) cells, shape the immune imbalance of IMN and promote the incidence and development of autoimmune responses. After reviewing the physiological knowledge of various subpopulations of Th cells and combining the existing studies on Th cells in IMN, the role model of Th cells in IMN was explained in this review. Finally, the existing clinical treatment regimens for IMN were reviewed, and the importance of the therapy for Th cells was highlighted.

Hypertensive nephropathy is the most common complication of hypertension, and is one of the main causes of end-stage renal disease (ESRD) in numerous countries. The basic pathological feature of hypertensive nephropathy is arteriolosclerosis followed by renal parenchymal damage. The etiology of this disease is complex, and its pathogenesis is mainly associated with renal hemodynamic changes and vascular remodeling. Despite the increased knowledge on the pathogenesis of hypertensive nephropathy, the current clinical treatment methods are still not effective in preventing the development of the disease to ESRD. Herbal medicine, which is used to relieve symptoms, can improve hypertensive nephropathy through multiple targets. Since there are few clinical studies on the treatment of hypertensive nephropathy with herbal medicine, this article aims to review the progress on the basic research on the treatment of hypertensive nephropathy with herbal medicine, including regulation of the renin angiotensin system, inhibition of sympathetic excitation, antioxidant stress and anti-inflammatory protection of endothelial cells, and improvement of obesity-associated factors. Herbal medicine with different components plays a synergistic and multi-target role in the treatment of hypertensive nephropathy. The description of the mechanism of herbal medicine in the treatment of hypertensive nephropathy will contribute towards the progress of modern medicine.

Idiopathic membranous nephropathy (IMN) is a pathological pattern of glomerular damage caused by an autoimmune response. Immune complex deposition, thickness of glomerular basement membrane, and changes in the podocyte morphology are responsible for the development of proteinuria, which is caused by the targeted binding of auto-antibodies to podocytes. Several auto-antigens have recently been identified in IMN, including M-type receptor for secretory phospholipase A2 (PLA2R1), thrombospondin type-1 domain-containing 7A (THSD7A), and neural epidermal growth factor-like 1 protein (NELL-1). The measurement of peripheral circulating antibodies has become an important clinical reference index. However, some clinical features of IMN remain elusive and need to be further investigated, such as the autoimmunity initiation, IgG4 predominance, spontaneous remission, and the unique glomerular lesion. As these unresolved issues are closely related to clinical practice, we have proposed a hypothetical pathogenesis model of IMN. Induced by environmental stimuli or other causes, the PLA2R1 antigen and/or THSD7A antigen exposed to extrarenal tissues, such as lungs, then produce the auto-antibodies that target and cause damage to the podocytes in circulation. In this review, we highlighted the potential association between environmental stimuli, immune activity, and glomerular lesions, the underlying basis for spontaneous immune and proteinuria remission.

Idiopathic membranous nephropathy (IMN) has made increasing progress in mechanism and treatment research. Herbal medicine is gradually being accepted as an alternative therapy in treating IMN. However, the intervention mechanism of herbal medicine in the treatment of membranous nephropathy is still unclear. In this review, we summarize some achievements of herb medicine in treating IMN and discuss the research direction of herb in IMN. Finally, we propose the dilemma about the study on the treatment of IMN with herb medicine. We hope that this article can bring some thoughts for clinical and scientific researchers on the treatment of IMN with herb medicine.

In idiopathic membranous nephropathy, the complement membrane attack complex, more commonly referred to as complement 5b-9 (C5b-9), induces glomerular epithelial cell injury and proteinuria. C5b-9 can also activate numerous mechanisms that restrict or facilitate injury. Recent studies suggest that autophagy and the canonical Wnt signaling pathway serve an important role in repairing podocyte injury. However, the effect of C5b-9 on these pathways and the relationship between them remains unclear. The aim of the present study was to show the effect of C5b-9 on the Wnt/β-catenin signaling pathway and autophagy in podocytes in vitro. Levels of relevant indicators were detected by immunofluorescence staining and capillary western immunoassay. C5b-9 serum significantly activated the Wnt/β-catenin signaling pathway and promoted autophagy. Treatment with Dickkopf-related protein 1 (DKK1), a Wnt/β-catenin pathway blocker, protected podocytes from injury and significantly inhibited autophagy. The results indicated that inhibition of the Wnt/β-catenin pathway physiologically activated autophagy. The results indicated that C5b-9 resulted in a decrease in Akt in podocytes. However, the podocytes preincubated with DKK1 and then attacked by C5b-9 showed an increase in Akt levels. This may explain the observation that blocking the Wnt/β-catenin signaling pathway attenuated C5b-9 podocyte damage, while inhibiting autophagy. The results of the present study also suggest that regulation of these two pathways may serve as a novel method for the treatment of idiopathic membranous nephropathy.

Membranous nephropathy (MN) is the major cause of nephrotic syndrome with special pathological features, caused by the formation of immune complexes in the space between podocytes and the glomerular basement membrane. In idiopathic membranous nephropathy (IMN) the immune complexes are formed by circulating antibodies binding mainly to one of two naturally-expressed podocyte antigens: the M-type receptor for secretory phospholipase A2 (PLA2R1) and the Thrombospondin type-1 domain-containing 7A (THSD7A). Formation of antibodies against PLA2R1 is much more common, accounting for 70-80% of IMN. However, the mechanism of anti-podocyte antibody production in IMN is still unclear. In this review, we emphasize that the exposure of PLA2R1 is critical for triggering the pathogenesis of PLA2R1-associated MN, and propose the potential association between inflammation, pollution and PLA2R1. Our review aims to clarify the current research of these precipitating factors in a way that may suggest future directions for discovering the pathogenesis of MN, leading to additional therapeutic targets and strategies for the prevention and early treatment of MN.