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Scientific Reports Jun 2024Chronic HIV disease is associated with a fivefold increase in albuminuria outside of sub-Saharan Africa. However, very little is known about albuminuria risk among... (Observational Study)
Observational Study
Chronic HIV disease is associated with a fivefold increase in albuminuria outside of sub-Saharan Africa. However, very little is known about albuminuria risk among people living with HIV (PLWH) in sub-Saharan Africa. Therefore, we conducted a cross-sectional observational HIV clinic-based study of albuminuria among 1533 adults aged 21 years or older between January 2020 and January 2021 in Gaborone, Botswana. Clinical albuminuria was defined using a sex-based albumin‒creatinine ratio (ACR) of 25-355 mg/g for females and 17-250 mg/g for males. The study population mean age was 48.5 (SD 10.3) years, and 764/1533 (49.7%) were female. The overall prevalence of albuminuria was 20.7% (95% CI 18.7%, 22.8%). A higher proportion of males were more likely to be categorized as having albuminuria than females, 25% (95% CI 22.0, 28.2) versus 16.4% (95% CI 13.8,19.2), P value < 0.001. In the final multivariate models, predictors of albuminuria differed by sex group. Larger longitudinal studies are required to evaluate the impact of albuminuria among PLWH with particular emphasis on the effect of sex on the risk of albuminuria.
Topics: Humans; Male; Albuminuria; HIV Infections; Middle Aged; Botswana; Adult; Female; Prevalence; Cross-Sectional Studies; Risk Factors; Young Adult
PubMed: 38910157
DOI: 10.1038/s41598-024-65099-w -
Journal For Immunotherapy of Cancer Jun 2024Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid...
BACKGROUND
Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers.
METHODS
We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR).
RESULTS
Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response.
CONCLUSION
Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation.
TRIAL REGISTRATION NUMBER
Chinese Clinical Trial Registry, ChiCTR1900023277.
Topics: Humans; Male; Female; Melanoma; Pyridines; Middle Aged; Antibodies, Monoclonal, Humanized; Aged; Adult; Antineoplastic Combined Chemotherapy Protocols; Mucous Membrane
PubMed: 38908858
DOI: 10.1136/jitc-2023-008611 -
Journal of Reproductive Immunology Jun 2024Abnormal placental angiogenesis during gestation resulting from high levels of anti-angiogenic factors, soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin,...
Abnormal placental angiogenesis during gestation resulting from high levels of anti-angiogenic factors, soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin, has been implicated in the progression of preeclampsia (PE). This heterogeneous syndrome (defined by hypertension with or without proteinuria after 20 weeks of pregnancy) remains a major global health burden with long-term consequences for both mothers and child. Previously, we showed that in vivo systemic human (hsFLT1) overexpression led to reduced placental efficiency and PE-like syndrome in mice. Galectins (gal-1, -3 and -9) are critical determinants of vascular adaptation to pregnancy and dysregulation of the galectin-glycan circuits is associated with the development of this life-threatening disease. In this study, we assessed the galectin-glycan networks at the maternal-fetal interface associated with the hsFLT1-induced PE in mice. We observed an increase on the maternal gal-1 expression in the decidua and junctional zone layers of the placenta derived from hs FLT1 pregnancies. In contrast, placental gal-3 and gal-9 expression were not sensitive to the hsFLT1 overexpression. In addition, O- and N-linked glycan expression, poly-LacNAc sequences and terminal sialylation were down-regulated in hsFLT1 placentas. Thus, the gal-1-glycan axis appear to play an important role counteracting the anti-angiogenic status caused by sFLT1, becoming critical for vascular adaptation at the maternal-fetal interface.
PubMed: 38908337
DOI: 10.1016/j.jri.2024.104284 -
BMC Cancer Jun 2024Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best...
PURPOSE
Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG.
METHODS
A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis.
RESULTS
The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction.
CONCLUSIONS
Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.
Topics: Humans; Temozolomide; Female; Male; Adult; Pyridines; Glioma; Adolescent; Retrospective Studies; Child; Brain Neoplasms; Young Adult; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Middle Aged; Treatment Outcome
PubMed: 38907215
DOI: 10.1186/s12885-024-12373-9 -
Nefrologia Jun 2024There is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the...
BACKGROUND
There is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the expression of C4d in FSGS subtypes in percutaneous native renal biopsies in a second-level hospital and its correlation with clinical, biochemical and histological variables.
MATERIAL AND METHODS
A retrospective study in paraffin blocks of patients with biopsy with FSGS aged 16-65 years, indistinct sex, not diabetic or obese. Immunohistochemistry was performed for C4d and their expression was analyzing in non-sclerosed glomerular capillaries (GC) and sclerosis areas (SA). Clinical and biochemical variables were recorded. The cases were divided into C4d positive and C4d negative groups and compared. The correlation between C4d staining scores in CG and SA with clinical and biochemical variables were analyzed.
RESULTS
Twenty samples were analyzed, 4 for each subtype. At the time of biopsy average age 38.8 ± 18.6 years, 65% male, 8.7% were hypertension. The percentage of positivity for C4d was 40% in GC, 30% SA and 35% in mesangium. The highest expression was for cellular and collapsing subtypes. C4d positivity cases had increased proteinuria (p = 0.035). A significant correlation was found between percentage of C4d expression in CG with SA (p = 0.012) and SA with tubular atrophy and interstitial fibrosis (p < 0.05).
CONCLUSIONS
C4d expression in FSGS predominated in the cellular and collapsing subtypes, which translates complement activation. C4d is a possible surrogate marker in GSFS.
PubMed: 38906767
DOI: 10.1016/j.nefroe.2023.04.007 -
Frontiers in Medicine 2024Fabry disease (FD) is an X-linked disorder resulting in a deficiency of α-galactosidase A (GLA) activity. The R112H mutation of GLA is relatively common in Japanese FD...
Fabry disease (FD) is an X-linked disorder resulting in a deficiency of α-galactosidase A (GLA) activity. The R112H mutation of GLA is relatively common in Japanese FD patients, characterized by a late-onset phenotype, almost normal to mild lyso-Gb3 elevation, and mild clinical symptoms, despite low GLA activity. This is due to the structural features of the R112H GLA protein. We herein report the case of a 42-year-old male patient with late-onset FD with a R112H mutation. The patient exhibited only renal involvement with no other organ damage and was successfully treated with galactosidase beta and subsequent migalastat for approximately 10 years. Especially, migalastat was clinically effective in normalizing plasma lyso-Gb3 levels and inhibiting the progression of renal damage associated with FD. Therefore, the use of migalastat in the FD patients with R112H mutation is highly recommended based on this case report.
PubMed: 38903807
DOI: 10.3389/fmed.2024.1383309 -
BMC Public Health Jun 2024Anaemia among preeclamptic (PE) women is a major undefined health issue in Bangladesh. This study explored the risk factors associated with anaemia and mapped the...
BACKGROUND
Anaemia among preeclamptic (PE) women is a major undefined health issue in Bangladesh. This study explored the risk factors associated with anaemia and mapped the regional influences to understand the geographical inequalities.
METHODS
Data from 180 respondents were prospectively collected from the Preeclampsia ward of Dhaka Medical College Hospital (DMCH), Bangladesh. Anaemia was defined as a blood haemoglobin level less than 11.0 g/dl. Preeclampsia was defined as systolic blood pressure (SBP) ≥ 140 mmHg and diastolic blood pressure (DBP) ≥ 90 mmHg with proteinuria. Factors associated with anaemia were explored using the chi-square test. Logistic regression (LR) was done to determine the level of association with the risk factors.
RESULTS
Among the participants, 28.9% were identified as having early onset and 71.1% reported late onset of PE. 38.9% of the subjects were non-anaemic, whereas mild, moderate, and severe anaemia was found among 38.3%, 17.8%, and 5% of patients respectively. The following factors were identified; including age range 25-34 (OR: 0.169, p < 0.05), a lower education level (OR: 3.106, p < 0.05), service-holder mothers (OR: 0.604, p < 0.05), pregnancy interval of less than 24 months (OR: 4.646, p < 0.05), and gestational diabetes mellitus (OR: 2.702, p < 0.05). Dhaka district (IR: 1.46), Narayanganj district (IR: 1.11), and Munshiganj district (IR: 0.96) had the highest incidence rates.
CONCLUSION
Determinants of anaemia must be considered with importance. In the future, periodic follow-ups of anaemia should be scheduled with a health care program and prevent maternal fatality and fetus morbidity in patients with PE.
Topics: Humans; Female; Bangladesh; Anemia; Pregnancy; Pre-Eclampsia; Adult; Cross-Sectional Studies; Risk Factors; Young Adult; Health Status Disparities; Socioeconomic Factors; Prospective Studies
PubMed: 38902634
DOI: 10.1186/s12889-024-18176-8 -
Nutrition & Diabetes Jun 2024Dietary-resistant starch is emerging as a potential therapeutic tool to limit the negative effects of diabetes on the kidneys. However, its metabolic and...
BACKGROUND
Dietary-resistant starch is emerging as a potential therapeutic tool to limit the negative effects of diabetes on the kidneys. However, its metabolic and immunomodulatory effects have not yet been fully elucidated.
METHODS
Six-week-old db/db mice were fed a diet containing 12.5% resistant starch or a control diet matched for equivalent regular starch for 10 weeks. db/m mice receiving the control diet were utilised as non-diabetic controls. Freshly collected kidneys were digested for flow cytometry analysis of immune cell populations. Kidney injury was determined by measuring albuminuria, histology, and immunohistochemistry. Portal vein plasma was collected for targeted analysis of microbially-derived metabolites. Intestinal histology and tight junction protein expression were assessed.
RESULTS
Resistant starch limited the development of albuminuria in db/db mice. Diabetic db/db mice displayed a decline in portal vein plasma levels of acetate, propionate, and butyrate, which was increased with resistant starch supplementation. Diabetic db/db mice receiving resistant starch had a microbially-derived metabolite profile similar to that of non-diabetic db/m mice. The intestinal permeability markers lipopolysaccharide and lipopolysaccharide binding protein were increased in db/db mice consuming the control diet, which was not seen in db/db mice receiving resistant starch supplementation. Diabetes was associated with an increase in the kidney neutrophil population, neutrophil activation, number of C5aR1+ neutrophils, and urinary complement C5a excretion, all of which were reduced with resistant starch. These pro-inflammatory changes appear independent of fibrotic changes in the kidney.
CONCLUSIONS
Resistant starch supplementation in diabetes promotes beneficial circulating microbially-derived metabolites and improves intestinal permeability, accompanied by a modulation in the inflammatory profile of the kidney including neutrophil infiltration, complement activation, and albuminuria. These findings indicate that resistant starch can regulate immune and inflammatory responses in the kidney and support the therapeutic potential of resistant starch supplementation in diabetes on kidney health.
Topics: Animals; Mice; Kidney; Albuminuria; Male; Neutrophil Infiltration; Diabetic Nephropathies; Resistant Starch; Gastrointestinal Microbiome; Starch; Diabetes Mellitus, Experimental; Mice, Inbred C57BL
PubMed: 38902253
DOI: 10.1038/s41387-024-00305-2 -
Biomedical Journal Jun 2024The incidence of autoimmune diseases is increasing in developed countries, possibly due to the modern Western diet and lifestyle. We showed earlier that polysaccharides...
BACKGROUND
The incidence of autoimmune diseases is increasing in developed countries, possibly due to the modern Western diet and lifestyle. We showed earlier that polysaccharides derived from the medicinal fungus Hirsutella sinensis produced anti-inflammatory, anti-diabetic and anti-obesity effects by modulating the gut microbiota and increasing the abundance of the commensal Parabacteroides goldsteinii in mice fed with a high-fat diet.
METHODS
We examined the effects of the prebiotics, H. sinensis polysaccharides, and probiotic, P. goldsteinii, in a mouse model of imiquimod-induced systemic lupus erythematosus.
RESULTS
The fungal polysaccharides and P. goldsteinii reduced markers of lupus severity, including the increase of spleen weight, proteinuria, and serum levels of anti-DNA auto-antibodies and signal transducer and activator of transcription 4 (STAT4). Moreover, the polysaccharides and P. goldsteinii improved markers of kidney and liver functions such as creatinine, blood urea nitrogen, glomerulus damage and fibrosis, and serum liver enzymes. However, the prebiotics and probiotics did not influence gut microbiota composition, colonic histology, or expression of tight junction proteins in colon tissues.
CONCLUSIONS
Our results indicate that H. sinensis polysaccharides and the probiotic P. goldsteinii can reduce lupus markers in imiquimod-treated mice. These prebiotics and probiotics may therefore be added to other interventions conducive of a healthy lifestyle in order to counter autoimmune diseases.
PubMed: 38901796
DOI: 10.1016/j.bj.2024.100754 -
Kidney & Blood Pressure Research Jun 2024The early diagnosis of kidney injury in type 2 diabetes (T2DM) is important to prevent the long-term damaging effects of kidney loss and is decisive for patient...
INTRODUCTION
The early diagnosis of kidney injury in type 2 diabetes (T2DM) is important to prevent the long-term damaging effects of kidney loss and is decisive for patient outcomes. While SIRT2 is implicated in diabetes pathogenesis, its correlation with diabetic nephropathy remains unexplored. This study was designed to evaluate the association of circulating and urine SIRT2 levels with diabetic kidney injury, as well as potential underlying mechanisms.
METHODS
In T2DM patients, db/db mice, and high-glucose plus palmitic acid treated HK-2 cell models, ELISA, immunoturbidimetry, immunohistochemistry, western blot and RT-qPCR were used to detect SIRT2 levels and kidneys damage. According to urinary albumin/creatinine ratio (UACR), 163 T2DM patients were divided into three groups. Spearman correlation analysis was used to investigate the relationship between urinary sirtuin2/creatinine ratio (USCR) and biomarkers of kidney injury. The influencing factors of proteinuria in T2DM patients were analyzed by Logistic regression model.
RESULTS
In our findings, the Macro group exhibited the highest USCR levels as UACR increased. There was a positive association between USCR and UACR, α1-microglobulin/creatinine ratio (UαCR), β2-microglobulin/creatinine ratio (UβCR), and retinol-binding protein/creatinine ratio (URCR), with a negative correlation observed with eGFR. Logistic ordered multiclassification regression analysis, adjusting for confounding variables, confirmed that USCR remained a significant risk factor for the severity of proteinuria in T2DM patients. In the kidney tissue of db/db mice, increased KIM-1 levels were associated with increased SIRT2 levels. Increased SIRT2 protein levels were also observed in renal tubular epithelial cells treated with high-glucose plus palmitic acid. Moreover, SIRT2 promotes the expression of pro-inflammatory factors TNF-α and IL-6 by modulating the phosphorylation of p38 MAPK and pJNK in renal tubular cells induced by high glucose and palmitic acid.
CONCLUSION
Urinary SIRT2 is closely related to eGFR, renal tubule injury and urinary albumin excretion in T2DM patients, which is expected to be an important indicator to comprehensively reflect renal injury.
PubMed: 38901411
DOI: 10.1159/000539886