Analytical Interference in Chemiluminescence Assay-Measured Angiotensin I, Angiotensin II, Aldosterone, and Renin.

BACKGROUND: The interference can be a significant source of laboratory errors with the potential to cause immunoassay results to drift. Therefore, we evaluated the interference in various endogenous and exogenous substances on immunoassay for angiotensin I (Ang I), angiotensin II (Ang II), aldosterone, and renin in vitro. METHODS: Ten endogenous and eight exogenous substances were evaluated at supraphysiologic or supratherapeutic plasma levels using the screening study to identify potential interfering substances. Subsequently, potential interfering substances were further tested within maximum pathological or therapeutic plasma concentration ranges using the dose-response study to determine whether the interference has a significant bias. According to preset acceptance criteria, the interference in potential interfering substances for Ang I, Ang II, and renin and aldosterone assays was determined. RESULTS: Six potential interfering substances for Ang I immunoassays were identified, namely valsartan, nifedipine, spironolactone, cholesterol, hemoglobin, and triglyceride. Meanwhile, ethanol, nifedipine, spironolactone, heparin sodium, warfarin, hemoglobin, uric acid, cholesterol, and triglyceride appeared to have potential interference in the Ang II assay. Three identified as possible interferents for aldosterone immunoassays were glucose, valsartan, and spironolactone. Moreover, warfarin, valsartan, spironolactone, uric acid, cholesterol, bilirubin unconjugated, triglyceride, and hemoglobin were potential interfering substances for renin immunoassays. However, only spironolactone of these potential interfering substances exceeded preset mean bias limits (less than ±10.0%) in aldosterone immunoassays. CONCLUSION: Exogenous spironolactone caused clinically significant interference in aldosterone immunoassays. Moreover, the interference in other substances was acceptable in Ang I, Ang II, and renin and aldosterone immunoassays.

Poly(Lysine)-Derived Carbon Quantum Dots Conquer Enterococcus faecalis Biofilm-Induced Persistent Endodontic Infections.

Introduction: Persistent endodontic infections (PEIs) mediated by bacterial biofilm mainly cause persistent periapical inflammation, resulting in recurrent periapical abscesses and progressive bone destruction. However, conventional root canal disinfectants are highly damaging to the tooth and periodontal tissue and ineffective in treating persistent root canal infections. Antimicrobial materials that are biocompatible with apical tissues and can eliminate PEIs-associated bacteria are urgently needed. Methods: Here, ε-poly (L-lysine) derived carbon quantum dots (PL-CQDs) are fabricated using pyrolysis to remove PEIs-associated bacterial biofilms. Results: Due to their ultra-small size, high positive charge, and active reactive oxygen species (ROS) generation capacity, PL-CQDs exhibit highly effective antibacterial activity against Enterococcus faecalis (E. faecalis), which is greatly dependent on PL-CQDs concentrations. 100 µg/mL PL-CQDs could kill E. faecalis in 5 min. Importantly, PL-CQDs effectively achieved a reduction of biofilms in the isolated teeth model, disrupting the dense structure of biofilms. PL-CQDs have acceptable cytocompatibility and hemocompatibility in vitro and good biosafety in vivo. Discussion: Thus, PL-CQDs provide a new strategy for treating E. faecalis-associated PEIs.

Fabrication of Bioresorbable Barrier Membranes from Gelatin/Poly(4-Hydroxybutyrate) (P4HB).

Dental implant surgery is a procedure that replaces damaged or missing teeth with an artificial implant. During this procedure, guided bone regeneration (GBR) membranes are commonly used to inhibit the migration of epithelium and GBR at the surgical sites. Due to its biodegradability, good biocompatibility, and unique biological properties, gelatin (GT) is considered a suitable candidate for guiding periodontal tissue regeneration. However, GT-based membranes come with limitations, such as poor mechanical strength and mismatched degradation rates. To confront this challenge, a series of GT/poly(4-hydroxybutyrate) (P4HB) composite membranes are fabricated through electrospinning technology. The morphology, composition, wetting properties, mechanical properties, biocompatibility, and in vivo biodegradability of the as-prepared composite membranes are carefully characterized. The results demonstrate that all the membranes present excellent biocompatibility. Moreover, the in vivo degradation rate of the membranes can be manipulated by changing the ratio of GT and P4HB. The results indicate that the optimized GT/P4HB membranes with a high P4HB content (75%) may be suitable for periodontal tissue engineering because of their good mechanical properties and biodegradation rate compatible with tissue growth.

Lead-imprinted polyvinylidene fluoride membrane for selective removal of lead from contaminated water: material fabrication, filtration application, and mechanism study.

The drinking water has become contaminated with lead in many countries across the world. In this study, a novel lead-imprinted polyvinylidene fluoride (PVDF) membrane was successfully fabricated for selective decontamination of lead from water. First of all, the membrane fabrication process was explored and optimized. The physical and chemical properties were then studied for a better understanding of the features of the membrane. The performance of lead removal by the adsorptive membrane was evaluated by systematic batch adsorption experiments, including pH effect, kinetics, isotherm, selectivity, and regeneration studies. The results indicated that the adsorptive membrane showed a high adsorption capacity of 40.59 mg Pb/g at the optimal pH of 5.5, fast kinetics of 2 h, high selectivity towards lead, and outstanding regeneration performance. The Langmuir equation fitted the isotherm better than the Freundlich equation, while the pseudo-second-order model and pore diffusion model well described the kinetics. The adsorptive membrane showed high selectivity towards lead in the lead/zinc binary solution. In the continuous filtration study, a small piece of adsorptive membrane could treat 3.75 L of lead solution. The XPS studies revealed that the lead uptake was mainly due to the complex reaction between lead and carboxyl and hydroxyl in the membrane.

A hydrogel-based first-aid tissue adhesive with effective hemostasis and anti-bacteria for trauma emergency management.

BACKGROUND: Clinical tissue adhesives remain some critical drawbacks for managing emergency injuries, such as inadequate adhesive strength and insufficient anti-infection ability. Herein, a novel, self-healing, and antibacterial carboxymethyl chitosan/polyaldehyde dextran (CMCS/PD) hydrogel is designed as the first-aid tissue adhesive for effective trauma emergency management. METHODS: We examined the gel-forming time, porosity, self-healing, antibacterial properties, cytotoxicity, adhesive strength, and hemocompatibility. Liver hemorrhage, tail severance, and skin wound infection models of rats are constructed in vivo, respectively. RESULTS: Results demonstrate that the CMCS/PD hydrogel has the rapid gel-forming (~ 5 s), good self-healing, and effective antibacterial abilities, and could adhere to tissue firmly (adhesive strength of ~ 10 kPa and burst pressure of 327.5 mmHg) with excellent hemocompatibility and cytocompatibility. This suggests the great prospect of CMCS/PD hydrogel in acting as a first-aid tissue adhesive for trauma emergency management. The CMCS/PD hydrogel is observed to not only achieve rapid hemostasis for curing liver hemorrhage and tail severance in comparison to commercial hemostatic gel (Surgiflo ®) but also exhibit superior anti-infection for treating acute skin trauma compared with clinical disinfectant gel (Prontosan ®). CONCLUSIONS: Overall, the CMCS/PD hydrogel offers a promising candidate for first-aid tissue adhesives to manage the trauma emergency. Because of the rapid gel-forming time, it could also be applied as a liquid first-aid bandage for mini-invasive surgical treatment.

Hypoxia mitigation by manganese-doped carbon dots for synergistic photodynamic therapy of oral squamous cell carcinoma.

Photodynamic therapy (PDT) is widely used for cancer treatment due to its non-invasive and precise effectiveness, however, hypoxia in the tumor microenvironment greatly limits the efficacy of photodynamic therapy. Compared with conventional photosensitizers, carbon dots (CDs) have great potential. Therefore, developing a water-soluble, low-toxicity photosensitizer based on CDs is particularly important, especially one that can enhance the photodynamic efficacy using the tumor microenvironment to produce oxygen. Herein, manganese-doped carbon dot (Mn-CDs, ∼2.7 nm) nanoenzymes with excellent biocompatibility were prepared by a solvothermal method using ethylenediaminetetraacetic acid manganese disodium salt hydrate and o-phenylenediamine as precursors. TEM, AFM, HR-TEM, XRD, XPS, FT-IR, ζ potential, DLS, UV-Vis, and PL spectra were used to characterize the Mn-CDs. Cancer resistance was assessed using the CCK-8 kit, calcein AM versus propidium iodide (PI) kit, and the Annexin V-FITC/PI cell apoptosis assay kit. The obtained Mn-CDs have excellent near-infrared emission properties, stability, and efficient 1O2 generation. Notably, the manganese doping renders CDs with catalase (CAT)-like activity, which leads to the decomposition of acidic H2O2 in situ to generate O2, enhancing the PDT efficacy against OSCC-9 cells under 635 nm (300 mW·cm-2) irradiation. Thus, this work provides a simple and feasible method for the development of water-soluble photosensitizers with oxygen production, presenting good biosafety for PDT in hypoxic tumors.

Carbon dots induce pathological damage to the intestine via causing intestinal flora dysbiosis and intestinal inflammation.

BACKGROUND: Carbon dots (CDs), as excellent antibacterial nanomaterials, have gained great attention in treating infection-induced diseases such as periodontitis and stomatitis. Given the eventual exposure of CDs to the intestine, elucidating the effect of CDs on intestinal health is required for the safety evaluation of CDs. RESULTS: Herein, CDs extracted from ε-poly-L-lysine (PL) were chosen to explore the modulation effect of CDs on probiotic behavior in vitro and intestinal remodeling in vivo. Results verify that PL-CDs negatively regulate Lactobacillus rhamnosus (L. rhamnosus) growth via increasing reactive oxygen species (ROS) production and reducing the antioxidant activity, which subsequently destroys membrane permeability and integrity. PL-CDs are also inclined to inhibit cell viability and accelerate cell apoptosis. In vivo, the gavage of PL-CDs is verified to induce inflammatory infiltration and barrier damage in mice. Moreover, PL-CDs are found to increase the Firmicutes to Bacteroidota (F/B) ratio and the relative abundance of Lachnospiraceae while decreasing that of Muribaculaceae. CONCLUSION: Overall, these evidences indicate that PL-CDs may inevitably result in intestinal flora dysbiosis via inhibiting probiotic growth and simultaneously activating intestinal inflammation, thus causing pathological damage to the intestine, which provides an effective and insightful reference for the potential risk of CDs from the perspective of intestinal remodeling.

Novel Y2O3 based calcium-alginate beads for highly selective adsorption of phosphate from aqueous solution.

Recently, selective phosphorus removal from aqueous solution has been a highly desirable strategy to combat eutrophication due to the increasingly stringent phosphorous emission standards. However, conventional adsorbents pose the limitations in phosphate removal suffering from lack of selectivity and stability under complicated condition and poor separation. In this study, novel Y2O3 based calcium-alginate (Y2O3/SA) beads of feasible stability and highly selectivity towards phosphate by encapsulating Y2O3 nanoparticles inside calcium-alginate beads via Ca2+ controlled gelation process was synthesized and characterized. The phosphate adsorption performance and mechanism were investigated. In general, a high selectivity among co-existing anions was found with co-existing anion concentration up to 62.5 times of the phosphate concentration. Additionally, phosphate adsorption by Y2O3/SA beads exhibited stable performance over a wide pH range between 2 and 10, while reaching the maximum adsorption capacity at pH 3 (48.54 mg-P/g). The value of point of zero charge (pHpzc) of Y2O3/SA beads was approximately 3.45. Pseudo-second-order and Freundlich isotherm models can well accord with kinetics and isotherms data. The FTIR and XPS characterizations analyzed that inner-sphere complexes were proposed to be the major contributor of Y2O3/SA beads for phosphate removal. In conclusion, Y2O3/SA beads as the mesoporous material exhibited excellent stability and selectivity towards phosphate removal.

Podocytes are likely the therapeutic target of IgA nephropathy with isolated hematuria: Evidence from repeat renal biopsy.

Background: The present study aimed to prove the progression of immunoglobulin A nephropathy (IgAN) patients with isolated hematuria based on repeat renal biopsy data for the first time. Methods: 29 IgAN patients with isolated hematuria who received repeat renal biopsies were analyzed retrospectively, while 29 non-isolated hematuria IgAN patients with similar age and background were randomly selected as the control group. Clinical parameters were collected at the time of biopsy. The treatment strategies (conservative treatment with RASS blocker or immunosuppressive treatment) were choosen according to the pathological results at the first renal biopsy. The activity and chronicity indexes of renal lesions were evaluated. Markers of cell inflammation and proliferation were tseted by immunochemistry. The ultrastructure of podocytes was observed by transmission electron microscopy (TEM). Podocyte and oxidative stress marker (NPHS2 and 4-HNE) were detected by immunofluorescence. Results: The IgAN patients with isolated hematuria had better clinical indicators than those with no-isolated hematuria, such as better renal function, higher albumin and lower uric acid. The interval between two biopsies in IgAN patients with isolated hematuria was 630 (interquartile range, 409.5-1,171) days. The hematuria of the patients decreased significantly from 30 (IQR, 4.00-35.00) RBC/ul in the first biopsy to 11 (IQR, 2.50-30.00) RBC/ul in the repeated biopsy (p < 0.05). The level of triglyceride decreased significantly (p < 0.05). The other clinical indicators were not statistically significant (p > 0.05). Deposits of IgA and C3 in the glomerulus were persistent. The activity index decreased, especially cellular crescent formation, while the chronicity index increased. The ultrastructure of podocytes was improved after treatment. The oxidative stress products of podocytes reduced after treatment. Conclusion: Although the clinical indicators of the IgAN patients with isolated hematuria were in the normal range, various acute and chronic pathological changes have occurred, and irreversible chronic changes have been progressing. Cell inflammation and proliferation persisted. Oxidative stress of podocytes was likely to be the therapeutic target. This study provided a strong basis for the progress of IgAN with isolated hematuria through pathological changes before and after treatment. This study will help clinicians recognize the harm of hematuria, change the traditional treatment concept, and help such patients get early treatment.

Efficacy and safety of sequential immunosuppressive treatment for severe IgA nephropathy: A retrospective study.

Background: This study compared the efficacy and safety of sequential immunosuppressive therapy in patients with non-end-stage IgA nephropathy (IgAN) with Lee's classification of IV ∼ V and provided evidence for the use of immunotherapy in patients with severe IgAN. Methods: We retrospectively analyzed the clinical data of patients with Lee's IV ∼ V non-end-stage IgA nephropathy. Results: 436 patients were diagnosed with IgAN, and 98 patients who met the inclusion criteria were included in this retrospective study. Of these, 17 were in the supportive care group, 20 in the P group (prednisone-only), 35 in P + CTX group (the prednisone combined with cyclophosphamide followed by mycophenolate mofetil), and 26 in the P + MMF group (prednisone combined with mycophenolate mofetil). The four groups showed differences in the segmental glomerulosclerosis score and the proportion of patients with Lee's grade IV (p < 0.05), but no differences in other indicators. Compared with the baseline values, urine protein-to-creatinine ratio (PCR) significantly decreased and serum albumin increased (p < 0.05), but there was no significant difference between the groups. The estimated Glomerular Filtration Rate (eGFR) of the P, P + MMF, and P + CTX groups were higher than that of the supportive care group at the 6th and 24th month after treatment (all p < 0.05). At the 24th month, the eGFR in the P + CTX group was higher than that in the P + MMF group (p < 0.05). The effective remission rate of the P + CTX group was higher than that of the supportive care group (p < 0.05). At 12 months, the effective remission rate of the P group was higher than that of the supportive care group (p < 0.05). At the 24th month, there was no significant difference in the effective remission rates among the three groups (P, P + MMF, and P + CTX). Nine patients with severe IgA nephropathy reached the endpoint. Conclusion: This study showed that immunosuppressive therapy insevere IgAN patient scan effectively reduce urinary protein, increase albumin, and protect renal function in the early stages of IgAN. P + CTX is the most commonly used, which has a high effective remission rate of urine protein and a low incidence of end-point events.

Risk factors for 1-year hospital readmissions in patients with systemic lupus erythematosus.

To reveal the characteristics of and risk factors for systemic lupus erythematosus (SLE) patients with frequent readmission aiming at intervening early and improve the quality of care during initial hospitalizations. This was a single-center, retrospective case-control study involving 521 hospitalized patients with SLE from January 2014 to December 2016 in the Affiliated Hospital of Guangdong Medical University. A total of 521 patients were enrolled, including 400 patients who were hospitalized once and 121 patients who were hospitalized repeatedly, and 23.2% of the patients were readmitted within 1 year. The results showed that the age of SLE onset (odds ratio [OR] 1.022, 95% confidence interval [CI] 1.007-1.036), serum albumin (OR 0.965, 95% CI 0.942-0.989), and cystatin C (OR 1.404, 95% CI 1.180-1.670) were closely related to readmission. The most common causes of readmission were infections (52 cases, 28.4%), especially respiratory tract infections, and lupus activity or recurrence (45 cases, 24.6%). Special attention should be paid to SLE patients with older age of onset, low serum albumin levels, and high cystatin C levels to avoid infection and recurrence with the aim of reducing the hospital readmission rate.

Effects of exercise interventions on cancer-related fatigue in breast cancer patients: an overview of systematic reviews.

OBJECTIVE: This overview of systematic reviews aims to critically appraise and consolidate evidence from current systematic reviews (SRs)/meta-analyses on the effects of exercise interventions on cancer-related fatigue (CRF) in breast cancer patients. METHODS: SRs/meta-analyses that explored the effects of exercise interventions on CRF in breast cancer patients compared with the routine methods of treatment and care were retrieved from nine databases. The methodological quality of the included SRs was appraised using A MeaSurement Tool to Assess systematic Reviews II (AMSTAR II). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to calculate the grading of outcomes in the included SRs. The exercise type, frequency, duration, and inclusion/absence of supervision were further evaluated with subgroup analyses. The Stata 16.0 software was utilized for data analysis. RESULTS: Twenty-nine reviews were included. The overall methodological quality and level of evidence of the included reviews were unsatisfactory, with only three reviews rated as high methodological quality and no review identified as high-quality evidence. Moderate certainty evidence indicated that exercise could improve fatigue in breast cancer patients (SMD = - 0.40 [95%CI - 0.58, - 0.22]; P = 0.0001). Subgroup analysis based on the types of exercise showed that yoga (SMD = - 0.30 [95%CI - 0.56, - 0.05]; I2 = 28.7%) and aerobic exercise (SMD = - 0.29 [95%CI - 0.56, - 0.02]; I2 = 16%) had a significantly better effect on CRF in breast cancer patients; exercising for over 6 months (SMD = - 0.88 [95%CI - 1.59, - 0.17]; I2 = 42.7%; P = 0.0001), three times per week (SMD = - 0.77 [95%CI - 1.04, - 0.05]; I2 = 0%; P = 0.0001), and for 30 to 60 min per session (SMD = - 0.81 [95%CI - 1.15, - 0.47]; I2 = 42.3%; P = 0.0001) can contribute to a moderate improvement of CRF. Supervised exercise (SMD = - 0.48 [95%CI - 0.77, - 0.18]; I2 = 87%; P = 0.001) was shown to relieve CRF. CONCLUSION: Exercise played a favorable role in alleviating CRF in breast cancer. Yoga was recommended as a promising exercise modality for CRF management in the majority of the included studies. Exercising for at least three times per week with 30 to 60 min per session could be recommended as a suitable dosage for achieving improvement in CRF. Supervised exercise was found to be more effective in alleviating CRF than unsupervised exercise. More rigorously designed clinical studies are needed to specify the exact exercise type, duration, frequency, and intensity to have an optimal effect on CRF in breast cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: CRD42020219866.

Revisited Cyclophosphamide in the Treatment of Lupus Nephritis.

Lupus nephritis (LN) is the most common serious complication of systemic lupus erythematosus (SLE). The pathogenesis of LN is complex, and the majority causes of LN are the renal deposition of circulating or/and in situ-formed immune complexes. These immune complexes trigger glomerular and tubulointerstitial inflammation, which finally leads to proteinuria and loss of renal function. Despite the emergence of new biological agents, cyclophosphamide (CY), an alkylating agent, is still the first-line drug widely used to treat patients with severe LN. In this review, we outline the application history, molecular structure, and pharmacokinetics of CY in the treatment of LN. We also detail its latest known immunopharmacological mechanisms, with a focus on supplemental regulation and inhibition of CD4 and CD8 positive T cells, differences in the use of various guidelines, and the combination with other drugs. The side effects of CY are also mentioned in this review.

IgA nephropathy patients with partial crescent formation benefit from immunosuppressants: evidence from repeat renal biopsy.

BACKGROUND: Crescent formation is a serious pathological change in the IgA nephropathy (IgAN) which is believed to be primarily mediated by a mixture of parietal epithelial cells, macrophages, and myofibroblasts. It was recommended that IgAN patients with rapid renal hypofunction with a crescent body >50% should begin treatment with corticosteroids combined with cyclophosphamide. However, for patients with partial crescent formation, whether immunosuppressive therapy is necessary is a contested topic. MATERIALS AND METHODS: Data from IgAN patients with partial crescent formation who underwent repeat renal biopsy were retrospectively analyzed. RESULTS: From the first to the second renal biopsy, the mean hemoglobin level and albumin level increased significantly (P < 0.05), and uric acid and triglyceride levels decreased significantly (P < 0.05). Also, the 24-hour urinary protein excretion decreased significantly (P < 0.001), but no differences in blood pressure, creatinine level, or estimated glomerular filtration rate. For pathological indices, there were no differences in fluorescence intensity of IgA or C3 deposition (P > 0.05), but the mesangial cell proliferation decreased significantly (P < 0.05), and the proportions of global glomerulosclerosis and tubulointerstitial fibrosis increased significantly (P < 0.05, respectively). In addition, a decreased tendency in the proportion of crescent formation was observed in the second renal biopsy. CONCLUSIONS: Immunosuppressive therapy for IgAN patients with partial crescent formation can reduce proteinuria, stabilize renal function, improve anemia, and mitigate acute kidney injury in the short term.

Increased number and activation of peripheral basophils in adult-onset minimal change disease.

Nowadays, the pathogenesis of minimal change disease (MCD) is still not well-known, and the current understanding on MCD is mainly based on data derived from children, and very few adults. Here, we comprehensively analysed the correlation between the changes of peripheral basophils and the incidence rate and relapse of adult-onset MCD. The results showed that in patients at the onset of MCD, the ratio and activation of basophils were all higher than those of healthy controls (all P < .05). In vitro test results showed that basophils from healthy controls can be activated by the serum taken from patients with MCD. Among 62 patients at the onset of MCD, with complete remission after treatment and 1 year of follow-up, the relative and absolute basophil counts before treatment were higher in the long-term remission group (n = 33) than that of the relapse group (n = 29). The basophil counts were significantly higher in the infrequent relapse group (n = 13) than that of the frequent relapse group (n = 16; P < .05). These findings suggested that basophil may play a pathogenic role in adult-onset MCD, and the increased number and activation of peripheral basophils could predict recurrence in adult MCD.

Updated advances of linking psychosocial factors and sex hormones with systemic lupus erythematosus susceptibility and development.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that primarily affects women, especially those of reproductive age. Genetics, environment, and gene-environment interactions play key roles in the development of SLE. Despite the numerous susceptibility genes of SLE identified to date, gene therapy is far from a clinical reality. Thus, more attention should be paid to the risk factors and underlying mechanisms of SLE. Currently, it is reported that psychosocial factors and sex hormones play vital roles in patients with SLE, which still need further investigated. The purpose of this review is to update the roles and mechanisms of psychosocial factors and sex hormones in the susceptibility and development of SLE. Based on review articles and reports in reputable peer-reviewed journals and government websites, this paper summarized psychosocial factors (e.g., alexithymia, depression, anxiety, negative emotions, and perceived stress) and sex hormones (e.g., estrogens, progesterone, androgens, and prolactin) involved in SLE. We further explore the mechanisms linking these factors with SLE susceptibility and development, which can guide the establishment of practical measures to benefit SLE patients and offer new ideas for therapeutic strategies.

Cross-regulation between exosomal and autophagic pathways: promising therapy targets in disease.

Exosomes are vesicles secreted by a variety of cell types. They can release their cargo into the extracellular environment or transfer their contents to other cells, as a form of intercellular communication. Therefore, exosomes are vital to both physiological and pathological functions. Autophagy is a process of intracellular degradation of unnecessary or dysfunctional cellular components such as damaged organelles and misfolded proteins. It is initiated by various environmental stressors and mediated by lysosomes. Under physiological conditions, autophagy exists in cells at basal levels to support cellular metabolism and help maintain self-homeostasis. In other circumstances, autophagy can contribute to the initiation and progression of disease. Recent studies have revealed that exosomal and autophagic pathways can be regulated by each other and play important roles in health and disease. However, the cross-regulation between these pathways is highly intricate, and the effects on exosomal trafficking and autophagy are environment-dependent. Here, we summarize the recent advances in understanding the cross-regulation between the exosomal and autophagic pathways, and their involvement in multiple diseases, which can help develop novel strategies for their prevention and treatment. From the evidence summarized in this review, we conclude: 1) exosomal trafficking plays a beneficial or harmful role in disease through the regulation of autophagy; 2) autophagy is vital in disease by regulating the generation of exosomes; and 3) the cross-regulation between exosomal and autophagic pathways may be promising targets for disease prevention and treatment, while this needs to be clarified in future investigations.

Current mechanistic insights into the role of infection in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by inflammation and abnormal production of autoantibody, but the mechanisms of the aberrant immune responses are currently unknown. Recently, growing evidence has suggested that infection plays a pivotal role in SLE. Here, we investigate the role of infectious agents (e.g., Epstein-Barr virus, parvovirus B19, human T-lymphotropic virus type 1, human immunodeficiency virus type 1, and endogenous retroviruses) in the pathogenesis of SLE. More importantly, we explore the known mechanisms underlying the involvement of infectious agents in the pathogenesis of SLE, including molecular mimicry, epitope spreading, superantigen production, bystander activation, persistent viral infection, altered apoptosis, clearance deficiency, and epigenetic alterations (e.g., DNA methylation and microRNAs). However, some infectious agents (e.g., malaria parasites, hepatitis B virus, Toxoplasma gondii, and Helicobacter pylori) may exert protective effects on SLE. Therefore, the relationship between infection and SLE is multifaceted and multidirectional, including causative and/or protective associations, which warrant further investigation in the future.