The bladder microbiome, metabolome, cytokines, and phenotypes in patients with systemic lupus erythematosus

Background and aims: Emerging studies reveal a unique bacterial community in the human bladder, with alteration of composition associated to disease states. Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by frequent impairment of the kidney. Here, we explored the bladder microbiome, metabolome, and cytokine profiles in SLE patients, as well as correlations between microbiome and metabolome, cytokines, and disease profiles. Methods and materials: We recruited a cohort of 50 SLE patients and 50 individually matched asymptomatic controls. We used transurethral catheterization to collect urine samples, 16S rRNA gene sequencing to profile bladder microbiomes, and LC-MS/MS to perform untargeted metabolomic profiling. Results: Compared to controls, SLE patients possessed a unique bladder microbial community and increased alpha diversity. These differences were accompanied by differences in urinary metabolomes, cytokines, and patients’ disease profiles. The SLE-enriched genera, including Bacteroides, were positively correlated with several SLE-enriched metabolites, including olopatadine. The SLE-depleted genera, such as Pseudomonas, were negatively correlated to SLE-depleted cytokines, including IL-8. Alteration of the bladder microbiome was associated with disease profile. For example, the genera Megamonas and Phocaeicola were negatively correlated with serum complement C3, and Streptococcus was positively correlated with IgG. Conclusions: Our present study reveals associations between the bladder microbiome and the urinary metabolome, cytokines, and disease phenotypes. Our results could help identify biomarkers for SLE.

Different Metabolomic and Proteomic Profiles of Cerebrospinal Fluid in Ventricular and Lumbar Compartments in Relation to Leptomeningeal Metastases

The different molecular profiles of cerebrospinal fluid (CSF) between ventricular and lumbar compartments remain elusive, especially in the context of leptomeningeal metastasis (LM), which affects CSF flow. We evaluated CSF metabolomic and proteomic profiles based on the compartments and the diagnosis of spinal LM, proved by MRI from 20 paired ventricular and lumbar CSF samples of LM patients, including 12 spinal LM (+) samples. In metabolome analysis, 9512 low-mass ions (LMIs) were identified—7 LMIs were abundant in all lumbar versus paired ventricular CSF samples, and 3 LMIs were significantly abundant in all ventricular CSF. In comparisons between spinal LM (+) CSF and LM (−) CSF, 105 LMIs were discriminative for spinal LM (+) CSF. In proteome analysis, a total of 1536 proteins were measured. A total of 18 proteins, including complement C3, were more highly expressed in all lumbar CSF, compared with paired ventricular CSF, while 82 proteins, including coagulation factor V, were higher in the ventricular CSF. Of 37 discriminative proteins, including uteroglobin and complement component C8 gamma chain, 4 were higher in all spinal LM (+) CSF versus spinal LM (−) CSF. We further evaluated metabolic pathways associated with these discriminative proteins using the Gene Ontology database. We found that 16/17 spinal LM (+) pathways, including complement activation, were associated with lumbar discriminative proteins, whereas only 2 pathways were associated with ventricular-discriminative proteins. In conclusion, we determined that metabolite and protein profiles differed between paired lumbar and ventricular CSF samples. The protein profiles of spinal LM (+) CSF showed more similarity with the lumbar CSF than the ventricular CSF. Thus, we suggest that CSF LMIs and proteins could reflect LM disease activity and that LM-associated differences in CSF are more likely to be present in the lumbar compartment.

Oral Administration of Nanopeptide CMCS-20H Conspicuously Boosts Immunity and Precautionary Effect Against Bacterial Infection in Fish

Massive mortalities caused by bacterial infections in intensive aquaculture result in serious economic losses. In this study, a novel antimicrobial peptide gcIFN-20H was efficiently expressed in Pichia pastoris (GS115) and loaded on carboxylmethyl chitosan (CMCS) to prepare CMCS-20H nanoparticles. Through physical characterization assays (TEM, DLS, BCA, and Raman) and biological activity tests (antimicrobial activity and cytotoxicity), CMCS-20H nanopeptide was verified to be spherical nanoparticles with sustained release, antimicrobial activity, and negligible toxicity. CMCS-20H nanoparticles are more resistant to intestinal degradation than unloaded gcIFN-20H by indirect immunofluorescence assay. Oral administration was then carried out for 42 days. Complement C3 content, lysozyme, and total superoxide dismutase activities are highest in CMCS-20H group by serum biochemistry index assays. After challenge with Aeromonas hydrophila, the survival rate in CMCS-20H group is highest (46%), which is 64% higher than the control group (28%). Meanwhile, the tissue bacterial loads (intestine, spleen, head kidney, trunk kidney, hepatopancreas, muscle, and blood) in the CMCS-20H group are significantly lower than other groups. By PAS staining analysis, the number of intestinal villi goblet cells and the thickness of mucin in the CMCS-20H group obviously increased. CMCS-20H effectively enhances mRNA expressions of some important immune genes (IL-1β, IL-6, TNF-α, IL-2, IFN-γ2, and IgM). The minimal tissue lesions (Intestine, spleen, and trunk kidney) were seen in the CMCS-20H group by histopathological examination. 16S rRNA sequencing showed that oral CMCS-20H maintains the intestinal microbiome homeostasis in bacterial infection. The results indicate that the novel nanopeptide CMCS-20H as the immunopotentiator can remarkably boost fish immunity and precautionary effect by oral administration and address the theoretical mechanisms and insights into the promising application prospect in aquaculture.

COVID-19: a trigger for severe thrombotic microangiopathy in a patient with complement gene variant

The evidence regarding thrombotic microangiopathy (TMA) related to Coronavirus Infectious Disease 2019 (COVID-19) in patients with complement gene mutations as a cause of acute kidney injury (AKI) are limited. We presented a case of a 23-year-old male patient admitted with an asymptomatic form of COVID-19, but with uncontrolled hypertension and AKI. Kidney biopsy showed severe lesions of TMA. In evolution patient had persistent microangiopathic hemolytic anemia, decreased level of haptoglobin and increased LDH level. Decreased complement C3 level and the presence of schistocytes were found for the first time after biopsy. Kidney function progressively decreased and the patient remained hemodialysis dependent. Complement work-up showed a heterozygous variant with unknown significance in complement factor I (CFI) c.-13G>A, affecting the 5' UTR region of the gene. In addition, the patient was found to be heterozygous for the complement factor H (CFH) H3 haplotype (involving the rare alleles of c.-331C>T, Q672Q and E936D polymorphisms) reported as a risk factor of atypical hemolytic uremic syndrome. This case of AKI associated with severe TMA and secondary hemolytic uremic syndrome highlights the importance of genetic risk modifiers in the alternative pathway dysregulation of the complement in the setting of COVID-19, even in asymptomatic forms.

Dietary Sodium, Potassium, and Sodium to Potassium Ratio in Patients With Systemic Lupus Erythematosus

Purpose: The aim of this study was to investigate the association between dietary sodium, potassium, and sodium:potassium ratio and clinical disease activity parameters, damage accrual, and cardiovascular disease risk factors in a population of patients with systemic lupus erythematous (SLE). Research design and study sample: A cross-sectional study including a total of 280 patients was conducted (90.4% females; mean age 46.9 ± 12.85 years). Data collection: The SLE Disease Activity Index (SLEDAI-2K) and the SDI Damage Index were used to assess disease activity and disease-related damage, respectively. A 24-hour diet recall was used to estimate dietary intake of sodium and potassium. Results: Dietary sodium intake was significantly associated with anti-dsDNA ( β = −.005; 95% CI [.002 .008]; p = .001) and complement C4 level ( β = −.002; 95% CI [−.003, .000]; p = .039). Dietary potassium intake was also significantly associated with complement C3 level ( β = −.004; 95% CI [−.007, −.001]; p = .021). Multiple logistic regression models revealed a positive association between dietary sodium intake and the risk of having hsCRP > 3 ( p = .005) and an inverse association between dietary potassium intake and the risk of having hsCRP > 3 ( p = .004). Conclusions: SLE patients with higher dietary sodium and lower dietary potassium intakes had an increased risk of higher hsCRP. Dietary sodium intake was significantly associated with anti-dsDNA and complement C4 level, while dietary potassium intake was associated with complement C3 level, supporting that dietary sodium and potassium intakes might play a key role in markers related to disease activity in SLE patients.

Oral Administration of Bacillus subtilis Subunit Vaccine Significantly Enhances the Immune Protection of Grass Carp against GCRV-II Infection

Grass carp reovirus (GCRV) is a severe virus that causes great losses to grass carp culture every year, and GCRV-II is the current popular and fatal strain. VP56, fibrin on the outer surface of GCRV-II, mediates cell attachment. In this study, we firstly divided the VP56 gene into four fragments to screen the optimal antigen by enzyme-linked immunosorbent assay and neutralizing antibody methods. The second fragment VP56-2 demonstrates the optimal efficiency and was employed as an antigen in the following experiments. Bacillus subtilis were used as a carrier, and VP56-2 was expressed on the surface of the spores. Then, we performed the oral immunization for grass carp and the challenge with GCRV-II. The survival rate was remarkably raised, and mRNA expressions of IgM were significantly up-regulated in spleen and head kidney tissues in the B. s-CotC-VP56-2 group. Three crucial immune indexes (complement C3, lysozyme and total superoxide dismutase) in the sera were also significantly enhanced. mRNA expressions of four important genes (TNF-α, IL-1β, IFN1 and MHC-II) were significantly strengthened. Tissue lesions were obviously attenuated by histopathological slide examination in trunk kidney and spleen tissues. Tissue viral burdens were significantly reduced post-viral challenge. These results indicated that the oral recombinant B. subtilis VP56-2 subunit vaccine is effective for controlling GCRV infection and provides a feasible strategy for the control of fish virus diseases.

Therapeutic possibilities of Bothrops jararaca in high dilution

Introduction: The knowledge and use of the venom of Bothrops jararaca in high dilutions is still quite limited. One of the important properties is the use of one of its components, bradykinin, for the development of antihypertensive medication known as captopril. Other situations, such as clinical, local and systemic should receive more depth to the composition of Materia Medica related to various medical actions on the man and mammals in general. The systemic action of the bite of this snake, includes hemostasis disorders, culminating as bleeding gums, in addition to sweating, hypertension, and hypothermia. The action includes local pain and swelling with bruising, bleeding and often blistering and tissue necrosis. The action on the immune system, through action on the complement C3 and other complement components may show its possible use in cases of bacterial infections, including mycobacteria, as presented in the study of 1970 Vanessa Birdsey, "Interactions of poisons toxic with the addition, "the journal of Immunology 1971. Today, this poison has a toxicology published by Anibal Melgarejo, "Venomous Animals of Brazil", 2003, which subsidizes the development of study for its use in high dilutions, and a comprehensive study of the biology of the animal itself. Published studies on biomolecular analysis add more details about the relations of the poison and mammals. All these characteristics suggest the use of poison as a homeopathic remedy. Objective: To investigate the therapeutic possibilities in high dilutions of the venom of the snake Bothrops jararaca, expanding its clinical use. Methodology: Methodological description of this poison in contemporary bases including: Origin, physical description chemistry, toxicology, pharmacology and medicine in preparation of high dilution, general action, specific actions on systems or organs, sensations, modalities, concomitants, etiological indications relations main clinics. Results: Defining the therapeutic indications such as modulation of the complement system, action on the cardiovascular system, among other uses, by Bothrops jararaca in high dilution. Conclusion: This evaluation can be used for different sources of products and allows the rational use of Bothrops jararaca in high dilution. The results can and should be complemented by clinical studies and pathogenetic. Bacterial infectious diseases such as tuberculosis and leprosy, and autoimmune disease LES and may receive treatment studies with the drug based on Bothrops jararaca snake venom because they are indirectly associated with them via similarity of the failure of complement, an important marker for bacterial the defense of mammals. Action on clinical aspects like hypertension, sweating, hypothermia and necrosis shall be seen. Perhaps the search for the stimulation of complement show a new pathway for the harmonization, long-predicted by Hahnemann, Hering and searched for among the many that followed the creator of this therapy.

Association of Cholinergic Basal Forebrain Volume and Functional Connectivity with Markers of Inflammatory Response in the Alzheimer’s Disease Spectrum

Background: Inflammation has been described as a key pathogenic event In Alzheimer’s disease (AD), downstream of amyloid and tau pathology. Preclinical and clinical data suggest that the cholinergic basal forebrain may moderate inflammatory response to different pathologies. Objective: To study the association of cholinergic basal forebrain volume and functional connectivity with measures of neuroinflammation in people from the AD spectrum. Methods: We studied 261 cases from the DELCODE cohort, including people with subjective cognitive decline, mild cognitive impairment, AD dementia, first degree relatives, and healthy controls. Using Bayesian ANCOVA, we tested associations of MRI indices of cholinergic basal forebrain volume and functional connectivity with cerebrospinal fluid (CSF) levels of sTREM2 as a marker of microglia activation, and serum levels of complement C3. Using Bayesian elastic net regression, we determined associations between basal forebrain measures and a large inflammation marker panel from CSF and serum. Results: We found anecdotal to moderate evidence in favor of the absence of an effect of basal forebrain volume and functional connectivity on CSF sTREM2 and serum C3 levels both in Aβ 42/ptau-positive and negative cases. Bayesian elastic net regression identified several CSF and serum markers of inflammation that were associated with basal forebrain volume and functional connectivity. The effect sizes were moderate to small. Conclusion: Our data-driven analyses generate the hypothesis that cholinergic basal forebrain may be involved in the neuroinflammation response to Aβ 42 and phospho-tau pathology in people from the AD spectrum. This hypothesis needs to be tested in independent samples.

Correlation Analysis of Chaige Qinlian Decoction and Acupuncture Combined Intervention on Prognosis of Children with Pneumonia

Background. Traditional Chinese medicine (TCM) treatment is of great importance to improve the clinical symptoms of children with pneumonia, and this study was conducted in this context. Methods. The clinical data of 82 child patients with pneumonia admitted to our hospital from February 2019 to February 2020 were retrospectively analyzed, and the patients were divided into the conventional group and the combined group according to the parity of their admission numbers, with 41 cases each. Conventional Western medicine therapy was given to children in the conventional group, and on this basis, acupuncture combined with Chaige Qinlian decoction was performed on children in the combined group, so as to evaluate the clinical application value of combined treatment and analyze its relationship with prognosis by recording the recovery time of each symptom, serum indicators, and immune indicators. Results. Children in the combined group had significantly shorter recovery time of each symptom and lower mean CPIS scores after treatment than the conventional group ( P < 0.001 ); the TCM symptom scores at T1 (1 d after treatment), T2 (3 d after treatment), T3 (7 d after treatment), and T4 (10 d after treatment) of children in the combined group were significantly higher than those in the conventional group ( P < 0.05 ); various immune indicators of the combined group before and after treatment were significantly different ( P < 0.001 ), and after treatment, the combined group obtained significantly higher IgG levels and lower IgA, complement C3, and complement C4 levels than the conventional group ( P < 0.001 ); and there was a positive correlation between the CPIS scores and serum IL-8, IL-6, and CRP levels at the first day (r = 0.706, 0.712, 0.734, P < 0.001 ). Conclusion. Acupuncture combined with Chaige Qinlian decoction can effectively shorten the course of disease, reduce the levels of serum inflammatory factors, and improve the immune function of body for child patients with pneumonia. Serum IL-8, IL-6, and CRP levels in child patients can reflect the clinical prognosis, with higher levels indicating worse prognosis.