Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

X-linked adrenoleukodystrophy(X-ALD) is an inherited progressive neurometabolic disorder caused by mutations in the ATP-binding cassette subfamily D member 1(ABCD1) gene. The encoded ALD protein dysfunction leads to the accumulation of very-long-chain fatty acids(VLCFA). X-ALD is classified according to its clinical characteristics into childhood cerebral ALD, adolescent cerebral ALD, adult cerebral ALD, adrenomyeloneuropathy(AMN), pure adrenocortical insufficiency, and an asymptomatic phenotype, all of which can present with a variety of neurologic manifestations. In this study, we retrospectively analyzed the clinical manifestations, laboratory findings, genetic test results, and follow-up data of four patients with X-ALD, and investigated the clinical features and pathogenicity of the identified gene mutations. All four patients initially presented with adrenocortical insufficiency(Addison′s disease) and received glucocorticoid replacement therapy. Subsequently, all developed neurologic signs and symptoms with rapid progression. The final diagnosis was confirmed based on elevated VLCFA levels, brain magnetic resonance imaging(MRI) findings, and genetic analysis. Notably, a deletion mutation in Exon 10 of the ABCD1 gene was identified in one case for the first time. We report four cases of X-ALD presenting with adrenocortical insufficiency as the initial symptom, and briefly review the relevant literature to analyze the relationship between linical phenotypes and genetic loci, aiming to provide a reference for early diagnosis and treatment of the disease, and to reduce the risk of misdiagnosis and missed diagnosis.

X-linked adrenoleukodystrophy(X-ALD) is an inherited progressive neurometabolic disorder caused by mutations in the ATP-binding cassette subfamily D member 1(ABCD1) gene. The encoded ALD protein dysfunction leads to the accumulation of very-long-chain fatty acids(VLCFA). X-ALD is classified according to its clinical characteristics into childhood cerebral ALD, adolescent cerebral ALD, adult cerebral ALD, adrenomyeloneuropathy(AMN), pure adrenocortical insufficiency, and an asymptomatic phenotype, all of which can present with a variety of neurologic manifestations. In this study, we retrospectively analyzed the clinical manifestations, laboratory findings, genetic test results, and follow-up data of four patients with X-ALD, and investigated the clinical features and pathogenicity of the identified gene mutations. All four patients initially presented with adrenocortical insufficiency(Addison′s disease) and received glucocorticoid replacement therapy. Subsequently, all developed neurologic signs and symptoms with rapid progression. The final diagnosis was confirmed based on elevated VLCFA levels, brain magnetic resonance imaging(MRI) findings, and genetic analysis. Notably, a deletion mutation in Exon 10 of the ABCD1 gene was identified in one case for the first time. We report four cases of X-ALD presenting with adrenocortical insufficiency as the initial symptom, and briefly review the relevant literature to analyze the relationship between linical phenotypes and genetic loci, aiming to provide a reference for early diagnosis and treatment of the disease, and to reduce the risk of misdiagnosis and missed diagnosis.

Objective:To describe the incidence and epidemiological characteristics of immune thrombocytopenia (ITP) in Gansu Province from 2019 to 2022, and provide evidence for the diagnosis and treatment of ITP, related etiological research, and the association between ITP and vaccination.Methods:Descriptive epidemiological method was used to describe the characteristics of new confirmed ITP cases during 2019-2022 by using the data collected from the electronic medical record database of Gansu.Results:A total of 4 159 cases of ITP were newly diagnosed in Gansu from 2019 to 2022; with an overall incidence of 4.11/100 000 (95% CI: 3.98/100 000- 4.23/100 000), the incidence was 3.49/100 000 in men (95% CI: 3.33/100 000-3.65/100 000), and 4.74/100 000 in women (95% CI: 4.56/100 000-4.94/100 000), the difference was significant ( P<0.001). The incidence in children and the elderly was high, and the risk for ITP was higher in boys aged <10 years and men aged ≥80 years than in girls, and the risk was higher in adult women (20- 69 years) than in adult men. The incidence peak of ITP occurred in summer (June, July and August), and the incidence trough was in February or October in Gansu, and the annual incidence level in each age group showed cyclical changes. The risk for ITP was high in eastern and western areas, and low in central area. Conclusions:The incidence of ITP were high in children and the elderly in Gansu in 2019-2022, and men were at higher risk for ITP compared with women, and higher risk for ITP was observed in women in total population. There were also seasonal and regional specific high incidence.

OBJECTIVE To prepare patchouli oil enteric-coated dropping pills, evaluate its colon-targeted release behaviors and therapeutic potency against rat ulcerative colitis(UC). METHODS The single factor combined with response surface optimization method was used to screen matrix types and optimize preparation process parameters. Formula and thickness of Eudragit coating was selected based on dissolution tendency toward simulated intestinal fluids. Finally, colon targeting release behavior and the therapeutic effect of the preparation were assessed on the rat UC model induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS). RESULTS The optimal prescription of patchouli oil dropping pills was patchouli oil∶PEG6000∶PEG8000 ratio of 1∶1∶1; and the optimal condition for preparing patchouli oil pills was keeping nozzle temperature at 9 ℃, and dropping pills at the speed of 33 drops·min−1, with dropping distance set at 6 cm; the optimal ratio of Eudragit L100∶Eudragit S100 was 3∶7 for preferential release in simulate intestinal fluid over simulated gastric fluid. Compared with free patchouli oil, patchouli oil enteric-coated dropping pills significantly alleviated the pathological symptoms such as weight loss, hematochezia and colon shortening in rats; the expression of pro-inflammatory cytokines IL-6, IL-1β, and IL-23 in serum was significantly down-regulated and the expression of anti-inflammatory cytokines IL-10 and TGF-β1 was significantly up-regulated. The mRNA expression of Mucin-1 and Mucin-2 in colon tissue was significantly up-regulated and the mRNA expression of inflammatory cytokines IL-6, IL-1β, and TNF-α was significantly down-regulated. CONCLUSION The patchouli oil enteric-coated dropping pills have colon-targeted release ability and improve the anti-inflammatory effect of drugs.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been a major health burden in the world. So far, many strategies have been investigated to control the spread of COVID-19, including social distancing, disinfection protocols, vaccines, and antiviral treatments. Despite the significant achievement, due to the constantly emerging new variants, COVID-19 is still a great challenge to the global healthcare system. It is an urgent demand for the development of new therapeutics and technologies for containing the wild spread of SARS-CoV-2. Inhaled administration is useful for the treatment of lung and respiratory diseases, and enables the drugs to reach the site of action directly with benefits of decreased dose, improved safety, and enhanced patient compliance. Nanotechnology has been extensively applied in the prevention and treatment of COVID-19. In this review, the inhaled nanomedicines and antibodies, as well as intranasal nanodrugs, for the prevention and treatment of COVID-19 are summarized.

[This corrects the article DOI: 10.1016/j.apsb.2021.09.004.].

Platelets buoy up cancer metastasis via arresting cancer cells, enhancing their adhesion, and facilitating their extravasation through the vasculature. When deprived of intracellular and granular contents, platelet decoys could prevent metastatic tumor formation. Inspired by these, we developed nanoplatesomes by fusing platelet membranes with lipid membranes (P-Lipo) to restrain metastatic tumor formation more efficiently. It was shown nanoplateletsomes bound with circulating tumor cells (CTC) efficiently, interfered with CTC arrest by vessel endothelial cells, CTC extravasation through endothelial layers, and epithelial-mesenchymal transition of tumor cells as nanodecoys. More importantly, in the mouse breast tumor metastasis model, nanoplateletsomes could decrease CTC survival in the blood and counteract metastatic tumor growth efficiently by inhibiting the inflammation and suppressing CTC escape. Therefore, nanoplatelesomes might usher in a new avenue to suppress lung metastasis.

The spread of coronavirus disease 2019 (COVID-19) throughout the world has resulted in stressful healthcare burdens and global health crises. Developing an effective measure to protect people from infection is an urgent need. The blockage of interaction between angiotensin-converting enzyme 2 (ACE2) and S protein is considered an essential target for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs. A full-length ACE2 protein could be a potential drug to block early entry of SARS-CoV-2 into host cells. In this study, a therapeutic strategy was developed by using extracellular vesicles (EVs) with decoy receptor ACE2 for neutralization of SARS-CoV-2. The EVs embedded with engineered ACE2 (EVs-ACE2) were prepared; the EVs-ACE2 were derived from an engineered cell line with stable ACE2 expression. The potential effect of the EVs-ACE2 on anti-SARS-CoV-2 was demonstrated by both in vitro and in vivo neutralization experiments using the pseudovirus with the S protein (S-pseudovirus). EVs-ACE2 can inhibit the infection of S-pseudovirus in various cells, and importantly, the mice treated with intranasal administration of EVs-ACE2 can suppress the entry of S-pseudovirus into the mucosal epithelium. Therefore, the intranasal EVs-ACE2 could be a preventive medicine to protect from SARS-CoV-2 infection. This EVs-based strategy offers a potential route to COVID-19 drug development.

The heparin polysaccharide nanoparticles block the interaction between heparan sulfate/S protein and inhibit the infection of both wild-type SARS-CoV-2 pseudovirus and the mutated strains through pulmonary delivery.Image 1.