Chiral α-Aminophosphonates as Ligands in Copper-Catalyzed Asymmetric Oxidative Coupling of 2-Naphthols.

Chiral α-aminophosphonates with adjacent carbon and phosphonate stereogenic centers have been employed as ligands in the copper-catalyzed oxidative coupling of 2-naphthols, resulting in the production of chiral BINOLs in favorable yields and moderate to good enantiomeric excess. This represents the first application of chiral P-based ligands to enable such a transformation. The synthesis of these chiral α-aminophosphonate ligands offers a significant advantage over approaches that typically necessitate elaborate synthetic processes for chiral ligand production.

Eight-Membered Palladacycle Intermediate Enabled Synthesis of Cyclic Biarylphosphonates.

Transition-metal-catalyzed coupling reactions that involve the direct functionalization of insert C-H bond represent one of the most efficient strategies for forming carbon-carbon bonds. Herein, a palladium-catalyzed intramolecular C-H bond arylation of triaryl phosphates is reported to access seven-membered cyclic biarylphosphonate targets. The reaction is achieved via a unique eight-membered palladacyclic intermediate and shows good functional group compatibility. Meanwhile, the product can be readily converted into other valuable phosphate compounds.

Alectinib relieves ischemic strokes caused by left atrial metastasis in a NSCLC patient with a novel SLC34A2-ALK (exon 1: exon 15) fusion.

BACKGROUND: The adoption of molecular profiling in non-small cell lung cancers (NSCLC) have promoted the discoveries of novel anaplastic lymphoma kinase (ALK) mutation patterns including rare intergenic rearrangements. It is always meaningful to report the structure of these fusions and their responses to ALK-inhibitors for future reference. Reports of cerebral ischemic strokes caused by atrial metastases through lymphohematogeneous spread are scarce. CASE PRESENTATION: A 35-year-old woman with no history of astherosclerosis presented with sudden onset of diplopia and facial palsy. Brain MRI scan discovered multiple infarcts around cortical and subcortical areas supplied by bilateral middle cerebral arteries, the occlusions of which were confirmed by angiography. Echocardiogram revealed intracavity appendages in atriums. The histology following valve debridement displayed endocardial metastases from lung cancer on mitral and trucuspid valves. PET/CT found right lower lobe primary tumor and mediastinal lymphadenopathies. The histology of primary lung tumor suggested adenocarcinoma and a DNA-based next-generation sequencing (NGS) test uncovered an intergenic (FAM49A, RAD51AP2)-ALK (intergenic: A14) rearrangement. Further RNA-based NGS uncovered a novel SLC34A2-ALK (exon 1: exon 15) fusion. Strokes recurred after valve surgery and vegetations reappeared on the mitral valve. Alectinib 600 mg bid was administered based on molecular finding and achieved remarkable tumor regression. Neurologic symptoms were largely relieved. No new infarctions or cerebral metastases has ever been found since. CONCLUSIONS: We report a novel SLC34A2-ALK rearrangement responding well to alectinib in a very interesting case of peripheral lung adenocarcinoma presenting with recurrent cerebral ischemic strokes due to endocardial metastases.

Clinical characteristics and immune profiles of patients with immune-mediated alopecia associated with COVID-19 vaccinations.

BACKGROUND: The clinical characteristics and pathomechanism for immune-mediated alopecia following COVID-19 vaccinations are not clearly characterized. OBJECTIVE: We investigated the causality and immune mechanism of COVID-19 vaccines-related alopecia areata (AA). STUDY DESIGN: 27 new-onset of AA patients after COVID-19 vaccinations and 106 vaccines-tolerant individuals were enrolled from multiple medical centers for analysis. RESULTS: The antinuclear antibody, total IgE, granulysin, and PARC/CCL18 as well as peripheral eosinophil count were significantly elevated in the patients with COVID-19 vaccines-related AA compared with those in the tolerant individuals (P = 2.03 × 10-5-0.039). In vitro lymphocyte activation test revealed that granulysin, granzyme B, and IFN-γ released from the T cells of COVID-19 vaccines-related AA patients could be significantly increased by COVID-19 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P = 0.002-0.04). CONCLUSIONS: Spike protein and excipients of COVID-19 vaccines could trigger T cell-mediated cytotoxicity, which contributes to the pathogenesis of immune-mediated alopecia associated with COVID-19 vaccines.

Metformin increases pathological responses to rectal cancers with neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.

BACKGROUND: To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N downstaging. METHODS: PubMed, MEDLINE, Embase, and Cochrane Database of collected reviews were searched up to June 30, 2022. This study conducted systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) sheet. Odds ratios (ORs) and confidence intervals (CIs) which calculated by random-effects models were displayed in forest plots. Newcastle-Ottawa scale was used to assess the risk of bias of the observational cohort studies. RESULTS: This systematic review and meta-analysis comprised eight cohorts out of seven studies, with 2294 patients in total. We performed two-way comparison for metformin in diabetic patients vs (1) non-metformin drugs in diabetic patients and (2) nondiabetic patients. In diabetes patient studies, the metformin group had a significantly increased pathological response on TRG (OR: 3.28, CI: 2.01-5.35, I2 = 0%, p < 0.001) and T downstaging (OR: 2.14, CI: 1.24-3.67, I2 = 14%, p = 0.006) in comparison with a non-metformin group. When compared with nondiabetic patients, the pathological response on TRG (OR: 2.67, CI: 1.65-4.32, I2 = 43%, p < 0.001) and T downstaging (OR: 1.96, CI: 1.04-3.71, I2 = 66%, p = 0.04) were also higher in metformin group. The limitation was that no randomized controlled trials were available based on current literature review. Small sample sizes for diabetic metformin or non-metformin users in rectal cancer patients reduced the power of the study. CONCLUSIONS: For patients with rectal cancer and treated with neoadjuvant chemoradiotherapy, metformin administration in diabetic patients increased the pathological response on tumor-regression grade and T downstaging. Further well-designed, high-quality randomized controlled trials are required to reveal the actual effect of metformin.

Prediction of Male Coronary Artery Bypass Grafting Outcomes Using Body Surface Area Weighted Left Ventricular End-diastolic Diameter: Multicenter Retrospective Cohort Study.

BACKGROUND: The presence of a high left ventricular end-diastolic diameter (LVEDD) has been linked to a less favorable outcome in patients undergoing coronary artery bypass grafting (CABG) procedures. However, by taking into consideration the reference of left ventricular size and volume measurements relative to the patient's body surface area (BSA), it has been suggested that the accuracy of the predicting outcomes may be improved. OBJECTIVE: We propose that BSA weighted LVEDD (bLVEDD) is a more accurate predictor of outcomes in patients undergoing CABG compared to simply using LVEDD alone. METHODS: This study was a comprehensive retrospective cohort study that was conducted across multiple medical centers. The inclusion criteria for this study were patients who were admitted for treatment between October 2016 and May 2021. Only elective surgery patients were included in the study, while those undergoing emergency surgery were not considered. All participants in the study received standard care, and their clinical data were collected through the institutional registry in accordance with the guidelines set forth by the Society of Thoracic Surgeons National Adult Cardiac Database. bLVEDD was defined as LVEDD divided by BSA. The primary outcome was in-hospital all-cause mortality (30 days), and the secondary outcomes were postoperative severe adverse events, including use of extracorporeal membrane oxygenation, multiorgan failure, use of intra-aortic balloon pump, postoperative stroke, and postoperative myocardial infarction. RESULTS: In total, 9474 patients from 5 centers under the Chinese Cardiac Surgery Registry were eligible for analysis. We found that a high LVEDD was a negative factor for male patients' mortality (odds ratio 1.44, P<.001) and secondary outcomes. For female patients, LVEDD was associated with secondary outcomes but did not reach statistical differences for morality. bLVEDD showed a strong association with postsurgery mortality (odds ratio 2.70, P<.001), and secondary outcomes changed in parallel with bLVEDD in male patients. However, bLVEDD did not reach statistical differences when fitting either mortality or severer outcomes in female patients. In male patients, the categorical bLVEDD showed high power to predict mortality (area under the curve [AUC] 0.71, P<.001) while BSA (AUC 0.62) and LVEDD (AUC 0.64) both contributed to the risk of mortality but were not as significant as bLVEDD (P<.001). CONCLUSIONS: bLVEDD is an important predictor for male mortality in CABG, removing the bias of BSA and showing a strong capability to accurately predict mortality outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02400125; https://clinicaltrials.gov/ct2/show/NCT02400125.

Engineering of dendritic mesoporous silica nanoparticles for efficient delivery of water-insoluble paclitaxel in cancer therapy.

The efficacy of hydrophobic chemotherapy drugs in cancer treatment is often hampered by their poor solubility in the physiological environment, which causes their low delivery efficiency in the body. This manuscript develops an intelligent nanocarrier (~100 nm) drug delivery system that can highly load a water-insoluble drug, and possesses desirable tumor-targeting properties for cancer therapy. In this system, highly porous silica nanoparticles (pore volume ~ 1.4 cm3 g-1) with a dendritic pore structure (denoted as DMSN) are applied as a matrix for drug loading. A facile, vacuum rotary evaporation-mediated casting method is applied to quantitatively load a high content of a hydrophobic drug (i.e., paclitaxel) in the DMSN matrix. A thiol-modified poly(methacrylic acid) (denoted as PMAsh) shell is then assembled and crosslinked via disulfide bonds on the particle surface to improve the dispersibility of the particles in an aqueous environment. After functionalization of the PMAsh shell with the targeting ligand transferrin (Tf), the nanocarriers exhibit accumulation ability on tumor cells, both in vitro and in vivo. Combining the fascinating properties of high drug-loading, excellent colloidal stability, low cytotoxicity, targeting ability and glutathione-responsive PMAsh shell deconstruction properties, the nanocarriers described here hold great promise for the efficient delivery of hydrophobic drugs and tumor treatment.

The Efficacy of Lactobacillus-Containing Probiotic Supplementation in Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVES: This study was performed to determine the effects of probiotic supplementation on cholesterol-triglyceride ratio, an indirect marker of insulin resistance, protein-bound uremic toxins, biomarkers of inflammation, and microbial translocation in end-stage renal disease patients on hemodialysis. METHODS: Fifty-six patients aged 39-75 years were assigned into two groups to receive either probiotic sachets (n = 28) or a placebo (n = 28) in a randomized double-blinded placebo-controlled clinical trial. The patients in the probiotic group received twice daily sachets that contained a mixture of three viable and freeze-dried strains: Lactococcus lactis subsp. Lactis LL358, Lactobaccillus salivarius LS159, and Lactobaccillus pentosus LPE588 at high dose (100 billion; 1 × 1011 cfu/day) for 6 months. RESULTS: A total of 50 patients were available for final analysis. Probiotic supplementation did not have a significant influence on cholesterol-triglyceride ratio. Probiotic supplementation for 6 months caused a significant decrease in serum levels of indoxyl sulfate. Compared with the placebo, probiotic supplementation did not result in significant changes in hemoglobin levels, blood urea nitrogen, blood glucose, serum p-cresyl sulfate, inflammatory, and microbial translocation markers. No clinically significant changes in body composition were observed between the two groups during the study period. The probiotic supplementation was well tolerated by all subjects with minimal adverse effects during the 6-month-long study. CONCLUSION: Our results suggest that high-dose multistrain lactobaccillus probiotic supplementation over 6 months as a monotherapy did not significantly decrease markers of insulin resistance, cholesterol-triglyceride ratio, and most of the studied markers, with the exception of levels of indoxyl sulfate in patients on HD.

Disseminated intravascular coagulation in Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: Patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have high mortality rates. Disseminated intravascular coagulation has been reported in SJS/TEN patients. The influence of this lethal complication in patients with SJS/TEN is not well known. OBJECTIVE: This study aimed to investigate the risk and outcomes of disseminated intravascular coagulation in patients with SJS/TEN. METHODS: We analyzed the disseminated intravascular coagulation profiles of patients receiving a diagnosis of SJS/TEN between 2010 and 2019. RESULTS: We analyzed 150 patients with SJS/TEN (75 with SJS, 22 with overlapping SJS/TEN, and 53 with TEN) and their complete disseminated intravascular coagulation profiles. Disseminated intravascular coagulation was diagnosed in 32 patients (21.3%), primarily those with TEN. It was significantly associated with systemic complications, including gastrointestinal bleeding, respiratory failure, renal failure, liver failure, infection, and bacteremia. Additionally, SJS/TEN patients with disseminated intravascular coagulation had elevated procalcitonin levels. Among patients with SJS/TEN, disseminated intravascular coagulation was associated with a greater than 10-fold increase in mortality (78.1% vs 7%). LIMITATIONS: The study limitations include small sample size and a single hospital system. CONCLUSION: Disseminated intravascular coagulation is a potential complication of SJS/TEN and associated with higher mortality. Early recognition and appropriate management of this critical complication are important for patients with SJS/TEN.

Development and validation of a multifrequency bioimpedance spectroscopy equation to predict appendicular skeletal muscle mass in hemodialysis patients.

BACKGROUND & AIMS: The Body Composition Monitor (BCM), a multifrequency bioimpedance spectroscopy device, has been widely used to assess body composition in hemodialysis patients because its measurement is not affected by overhydration commonly seen in chronic kidney disease. We aimed to develop and validate an equation for obtaining appendicular skeletal muscle mass (ASM) from BCM taking dual-energy X-ray absorptiometry (DXA) as the reference among hemodialysis patients. METHODS: A total of 322 consecutive body composition measurements with BCM and DXA in 263 hemodialysis patients were randomly divided at a ratio of 2:1 into development and validation groups. Stepwise multiple regression modeling was applied to develop the ASM prediction equation. We evaluated the model as a diagnostic tool for sarcopenia using cutoffs of ASM defined by the Asian Working Group for Sarcopenia (AWGS). We further explored the association between ASM predicted by the BCM equation and all-cause mortality in two independent cohorts: one with 326 stage 3-5 CKD patients and one with 629 hemodialysis patients. RESULTS: BCM yielded the following equation: ASM (kg) = -1.838 + 0.395 × total body water (L) + 0.105 × body weight (kg) + 1.231 × male sex - 0.026 × age (years) (R2 = 0.914, standard error of estimate = 1.35 kg). In the validation group, Bland-Altman reliability analysis showed no significant bias of 0.098 kg and limits of agreement ±2.440 kg. Using the AWGS criteria, the model was found to have a sensitivity of 94.1%, a specificity of 98.8%, a positive predictive value of 84.2%, and a negative predictive value of 99.6% for the diagnosis of sarcopenia. Low ASM predicted by the BCM equation was associated with significantly worse overall survival among CKD patients but not hemodialysis patients. CONCLUSIONS: The new BCM equation provides a feasible and valid option for assessing ASM in hemodialysis patients.

Attenuation of Wnt/ß-catenin signaling in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) are rare but life-threatening severe cutaneous adverse reactions. Current studies have suggested that the pathobiology of drug-mediated SJS/TEN involves a dysregulation of cellular immunity with overwhelming activation of cytotoxic T lymphocytes. The canonical Wnt signaling pathway plays important roles in T cell development and activation, which may provide potential avenues for alleviating dysregulated immunity in SJS/TEN. In this study, we aimed to assess the implication of Wnt signaling in drug-reactive T cells in SJS/TEN. We showed downregulation of Wnt signaling components, including T cell factor 1 (TCF-1)/lymphoid enhancer binding factor 1 (LEF-1) transcription factors, in SJS/TEN patients, suggesting that canonical Wnt signaling is regulated during cytotoxic T cell responses in SJS/TEN. Further analyses demonstrated that engagement of the T cell receptor by antigen encounter and treatment of a prognostic marker of SJS/TEN, IL-15, in vitro led to the downregulation of LEF-1 and TCF-1 expression in CD8+ T cells. Enhancement of Wnt signaling by adding the Wnt activators attenuated ex vivo activation of drug-specific T cells from SJS/TEN patients, indicating a functional involvement of Wnt signaling in the pathomechanism of SJS/TEN. These findings provide additional insight into the immunopathogenesis and therapeutic intervention of this devastating condition.

Change in body weight and body mass index in psoriasis patients receiving biologics: A systematic review and network meta-analysis.

BACKGROUND: Previous studies have suggested that biologic therapy for psoriasis might relate to body weight gain. OBJECTIVE: To assess the changes in body weight and body mass index (BMI) in psoriasis patients after receiving various biologics. METHODS: We conducted a systematic review and network meta-analysis to evaluate the changes in body weight and BMI in psoriasis patients receiving biologics. On March 1, 2019, we searched Medline, Embase, and Cochrane Central Register of Controlled Trials for relevant studies. The Newcastle-Ottawa scale was used to assess the risk of bias. RESULTS: We included 6 studies with 862 psoriasis patients. Compared with conventional systemic treatments, treatment with tumor necrosis factor α inhibitors was associated with a significant increase in body weight (mean difference 1.40 kg, 95% confidence interval 0.88-1.93 kg) and BMI (0.39 kg/m2, 95% confidence interval 0.24-0.54 kg/m2). In contrast, no significant increase in body weight or BMI was found among patients receiving anti-interleukin (IL)-12/23 or anti-IL-17 biologics. LIMITATIONS: Only 1 study reported body weight and BMI for patients receiving the anti-IL-17 biologic. CONCLUSION: Tumor necrosis factor α inhibitor treatment appears to be associated with an increase in body weight and BMI, and treatment with anti-IL-12/23 and anti-IL-17 biologics do not. This association should be considered before initiating biologics for overweight and obese patients.

Psoriasiform drug eruption secondary to sorafenib: case series and review of the literature.

The expanding use of novel targeted anticancer agents such as sorafenib has led to an increasing number of dermatologic adverse events. Although cutaneous adverse events are commonly described in patients taking sorafenib, there are few reports describing psoriasis secondary to this medication. In this report, we describe 3 patients with sorafenib-induced psoriasiform drug eruption and review the available literature of similar patient cases. Our findings highlight shared characteristics among affected patients and potential treatment options for patients in whom sorafenib cannot be discontinued. Increased awareness of such drug eruptions and management options is critical to prevent suboptimal dosing and decreased quality of life.

Development of SSR markers for Astragalus lehmannianus, a vulnerable species from northwestern China.

PREMISE: Astragalus lehmannianus (Fabaceae) is a vulnerable species found in the cold deserts of northwestern China. We aimed to characterize polymorphic microsatellite loci for A. lehmannianus to support future studies of population genetic dynamics and conservation management of the species. METHODS AND RESULTS: We used next-generation sequencing to detect polymorphic microsatellites. Twenty-five potential microsatellite loci were identified, 12 of which were polymorphic and present in the three study populations of A. lehmannianus. Levels of observed and expected heterozygosities were 0.000-1.000 and 0.000-0.827, respectively. Furthermore, two and five of the 12 developed primers were successfully amplified in two congeneric species, A. arpilobus and A. oxyglottis, respectively. CONCLUSIONS: These newly developed microsatellite markers can be used to determine population diversity and to develop conservation strategies in A. lehmannianus.

The Role of Immune Checkpoint Receptors in Regulating Immune Reactivity in Lupus.

Immune checkpoint receptors with co-stimulatory and co-inhibitory signals are important modulators for the immune system. However, unrestricted co-stimulation and/or inadequate co-inhibition may cause breakdown of self-tolerance, leading to autoimmunity. Systemic lupus erythematosus (SLE) is a complex multi-organ disease with skewed and dysregulated immune responses interacting with genetics and the environment. The close connections between co-signaling pathways and SLE have gradually been established in past research. Also, the recent success of immune checkpoint blockade in cancer therapy illustrates the importance of the co-inhibitory receptors in cancer immunotherapy. Moreover, immune checkpoint blockade could result in substantial immune-related adverse events that mimic autoimmune diseases, including lupus. Together, immune checkpoint regulators represent viable immunotherapeutic targets for the treatment of both autoimmunity and cancer. Therefore, it appears reasonable to treat SLE by restoring the out-of-order co-signaling axis or by manipulating collateral pathways to control the pathogenic immune responses. Here, we review the current state of knowledge regarding the relationships between SLE and the co-signaling pathways of T cells, B cells, dendritic cells, and neutrophils, and highlight their potential clinical implications. Current clinical trials targeting the specific co-signaling axes involved in SLE help to advance such knowledge, but further in-depth exploration is still warranted.

Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies.

With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morbidity and sequela. As a treatment guideline for this devastating condition is still unavailable, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we outline distinct types of SCARs caused by targeted anticancer therapies and immunotherapies. Also, we discuss the clinical course, latency, concomitant medication, tolerability of rechallenge or alternatives, tumor response, and mortality associated with these devastating conditions. Imatinib, vemurafenib, and rituximab were the top three offending medications that most commonly caused SJS/TEN, while EGFR inhibitors were the group of drugs that most frequently induced SJS/TEN. For drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis, imatinib was also the most common offending drug. Additionally, we delineated 10 SCAR cases related to innovative immunotherapies, including PD1 and CTLA4 inhibitors. There was a wide range of latency periods: 5.5-91 days (median). Only eight of 16 reported patients with SCAR showed clinical responses. Targeted anticancer drugs and immunotherapies can lead to lethal SCAR (14 deceased patients were identified as suffering from SJS/TEN). The mortality rate of TEN was high: up to 52.4%. The information compiled herein will serve as a solid foundation to formulate ideas for early recognition of SCAR and to discontinue offending drugs for better management.

Anticancer Drugs Induced Severe Adverse Cutaneous Drug Reactions: An Updated Review on the Risks Associated with Anticancer Targeted Therapy or Immunotherapies.

Cutaneous adverse drug reactions are commonly seen in patients with anticancer drug treatment. Anticancer drugs, including chemotherapy, target therapy, and recent immunotherapy causing skin reactions ranging from mild skin rash to life-threatening severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) with increase morbidity and mortality while they are receiving cancer treatments, have been proposed to be a result of direct skin toxicity or drug hypersensitivity reactions (these are proposed mechanism, not definite). Differentiating SCARs from other more commonly seen reactions with a better outcome help prevent discontinuation of therapy and inappropriate use of systemic immunosuppressants for presumable allergic reactions, of which will affect the clinical outcome. In this article, we have reviewed published articles from 1950 to August 2017 for SJS/TEN associated with anticancer drugs, including chemotherapy, targeted therapy, and immunotherapy. We aimed to provide an overview of SJS/TEN associated with anticancer drugs to increase clinician recognition and accelerate future studies on the pathomechanism and managements.

Impaired Gut Epithelial Tight Junction Expression in Hemodialysis Patients Complicated with Intradialytic Hypotension.

BACKGROUND: There is accumulating evidence pointing to uremia-induced impairment of the intestinal epithelial barrier structure in advanced chronic kidney disease (CKD) and hemodialysis (HD) patients. In this study, the impact of intradialytic hypotension on intestinal barrier integrity is being explored. METHODS: Immunohistochemical staining was used to detect the expression of 4 types of tight junction (TJ) proteins such as occludin, zonula occludens-1 (ZO-1), claudin-1, and claudin-4, in colonic samples of a group of patients receiving segmental colectomy. Five patients with nondialysis CKD (group 2), 5 HD patients with intradialytic hypotension (group 3), and 5 non-CKD subjects (group 1) were examined. RESULTS: Both patients' groups 2 and 3 demonstrated significantly reduced expression of occludin as compared to group 1 (p < 0.05 and p < 0.01, resp.). Except for claudin-4, expression of all markers of TJ proteins was significantly reduced in patients' group 3 as compared to control (p < 0.01). In addition, decreased expressions of claudin-1 and ZO-1 were also more pronounced in group 3 when compared to group 2. CONCLUSIONS: This study extends the earlier finding by demonstrating that dialysis-related hypotension caused even marked depletion of the key protein constituents of the epithelial TJ.