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1.
Parasite Immunol ; 46(3): e13032, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38497997

RESUMO

Cryptosporidium is an opportunistic protozoan, with many species of cross-human infectivity. It causes life-threatening diarrhoea in children and CD4-defective patients. Despite its limited efficacy, nitazoxanide remains the primary anti-cryptosporidial drug. Cryptosporidium infects the intestinal brush border (intracellular-extracytoplasmic) and down-regulates pyroptosis to prevent expulsion. Romidepsin is a natural histone deacetylase inhibitor that triggers pyroptosis. Romidepsin's effect on cryptosporidiosis was assessed in immunocompromised mice via gasdermin-D (GSDM-D) immunohistochemical expression, IFN-γ, IL-1ß and IL-18 blood levels by ELISA, and via parasite scanning by modified Ziehl-Neelsen staining and scanning electron microscopy (SEM). Oocyst deformity and local cytokines were also assessed in ex vivo ileal explants. Following intraperitoneal injection of romidepsin, oocyst shedding significantly reduced at the 9th, 12th and 15th d.p.i. compared with infected-control and drug-control (nitazoxanide-treated) mice. H&E staining of intestinal sections from romidepsin-treated mice showed significantly low intestinal scoring with marked reduction in epithelial hyperplasia, villous blunting and cellular infiltrate. SEM revealed marked oocyst blebbing and paucity (in vivo and ex vivo) after romidepsin compared with nitazoxanide. Regarding pyroptosis, romidepsin triggered significantly higher intestinal GSDM-D expression in vivo, and higher serum/culture IFN-γ, IL-1ß and IL-18 levels in romidepsin-treated mice than in the control groups. Collectively, in cryptosporidiosis, romidepsin succeeded in enhancing pyroptosis in the oocysts and infected epithelium, reducing infection and shifting the brush border towards normalisation.


Assuntos
Criptosporidiose , Cryptosporidium , Depsipeptídeos , Nitrocompostos , Tiazóis , Criança , Humanos , Animais , Camundongos , Criptosporidiose/tratamento farmacológico , Inibidores de Histona Desacetilases/farmacologia , Interleucina-18 , Piroptose
2.
Parasite Immunol ; 46(3): e13030, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38498004

RESUMO

In previous studies, the inhibitory effect of chloroquine on NLRP3 inflammasome and heme production was documented. This may be employed as a double-bladed sword in schistosomiasis (anti-inflammatory and parasiticidal). In this study, chloroquine's impact on schistosomiasis mansoni was investigated. The parasitic load (worm/egg counts and reproductive capacity index [RCI]), i-Nos/Arg-1 expression, splenomegaly, hepatic insult and NLRP3-immunohistochemical expression were assessed in infected mice after receiving early and late repeated doses of chloroquine alone or dually with praziquantel. By early treatment, the least RCI was reported in dually treated mice (41.48 ± 28.58) with a significant reduction in worm/egg counts (3.50 ± 1.29/2550 ± 479.58), compared with either drug alone. A marked reduction in the splenic index was achieved by prolonged chloroquine administration (alone: 43.15 ± 5.67, dually: 36.03 ± 5.27), with significantly less fibrosis (15 ± 3.37, 14.25 ± 2.22) than after praziquantel alone (20.5 ± 2.65). Regarding inflammation, despite the praziquantel-induced significant decrease in NLRP3 expression, the inhibitory effect was marked after dual and chloroquine administration (liver: 3.13 ± 1.21/3.45 ± 1.23, spleen: 5.7 ± 1.6/4.63 ± 2.41). i-Nos RNA peaked with early/late chloroquine administration (liver: 68.53 ± 1.8/57.78 ± 7.14, spleen: 63.22 ± 2.06/62.5 ± 3.05). High i-Nos echoed with a parasiticidal and hepatoprotective effect and may indicate macrophage-1 polarisation. On the flip side, the chloroquine-induced low Arg-1 seemed to abate immune tolerance and probably macrophage-2 polarisation. Collectively, chloroquine synergised the praziquantel-schistosomicidal effect and minimised tissue inflammation, splenomegaly and hepatic fibrosis.


Assuntos
Doenças dos Roedores , Esquistossomose mansoni , Animais , Camundongos , Cloroquina/farmacologia , Regulação para Baixo , Reposicionamento de Medicamentos , Inflamação , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Carga Parasitária , Praziquantel/farmacologia , Esquistossomose mansoni/tratamento farmacológico , Esplenomegalia
3.
Insect Sci ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531693

RESUMO

With the increasing development of nanomaterials, the use of nanodiamonds (NDs) has been broadly manifested in many applications. However, their high penetration into the ecosystem indubitably poses remarkable toxicological risks. This paper investigates the toxic effects of NDs on the darkling beetle, Blaps polychresta Forskal, 1775 (Coleoptera: Tenebrionidae). Survival analysis was carried out by monitoring the beetles for 30 d after the injection of four different doses of NDs. A dose of 10.0 mg NDs/g body weight, causing less than 50% mortality effect, was assigned in the analysis of the different organs of studied beetles, including testis, ovary, and midgut. Structural and ultrastructural analyses were followed using light, TEM, and SEM microscopes. In addition, a variety of stress markers and enzyme activities were assessed using spectrophotometric methods. Furthermore, cell viability and DNA damage were evaluated using cytometry and comet assay, respectively. Compared to the control group, the NDs-treated group was exposed to various abnormalities within all the studied organs as follows. Significant disturbances in enzyme activities were accompanied by an apparent dysregulation in the antioxidant system. The flow cytometry results indicated a substantial decrease of viable cells along with a rise of apoptotic and necrotic cells. The comet assay demonstrated a highly increased level of DNA damage. Likewise, histological analyses accentuated the same findings showing remarkable deformities in the studied organs. Prominently, the research findings substantially contribute for the first time to evaluating the critical effects of NDs on B. polychresta, adopted as the bioindicator in this paper.

4.
Biofilm ; 7: 100183, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38380422

RESUMO

Antibiotic-resistant biofilm infections have emerged as public health concerns because of their enhanced tolerance to high-dose antibiotic treatments. The biofilm life cycle involves multiple developmental stages, which are tightly regulated by active cell-cell communication via specific extracellular signal messengers such as extracellular vesicles. This study was aimed at exploring the roles of extracellular vesicles secreted by Pseudomonas aeruginosa at different developmental stages in controlling biofilm growth. Our results show that extracellular vesicles secreted by P. aeruginosa biofilms during their exponential growth phase (G-EVs) enhance biofilm growth. In contrast, extracellular vesicles secreted by P. aeruginosa biofilms during their death/survival phase (D-EVs) can effectively inhibit/eliminate P. aeruginosa PAO1 biofilms up to 4.8-log10 CFU/cm2. The inhibition effectiveness of D-EVs against P. aeruginosa biofilms grown for 96 h improved further in the presence of 10-50 µM Fe3+ ions. Proteomic analysis suggests the inhibition involves an iron-dependent ferroptosis mechanism. This study is the first to report the functional role of bacterial extracellular vesicles in bacterial growth, which depends on the developmental stage of the parent bacteria. The finding of D-EV-activated ferroptosis-based bacterial death may have significant implications for preventing antibiotic resistance in biofilms.

5.
J Biol Chem ; 300(2): 105645, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38218225

RESUMO

Glutathione (GSH) is a highly abundant tripeptide thiol that performs diverse protective and biosynthetic functions in cells. While changes in GSH availability are associated with inborn errors of metabolism, cancer, and neurodegenerative disorders, studying the limiting role of GSH in physiology and disease has been challenging due to its tight regulation. To address this, we generated cell and mouse models that express a bifunctional glutathione-synthesizing enzyme from Streptococcus thermophilus (GshF), which possesses both glutamate-cysteine ligase and glutathione synthase activities. GshF expression allows efficient production of GSH in the cytosol and mitochondria and prevents cell death in response to GSH depletion, but not ferroptosis induction, indicating that GSH is not a limiting factor under lipid peroxidation. CRISPR screens using engineered enzymes further revealed genes required for cell proliferation under cellular and mitochondrial GSH depletion. Among these, we identified the glutamate-cysteine ligase modifier subunit, GCLM, as a requirement for cellular sensitivity to buthionine sulfoximine, a glutathione synthesis inhibitor. Finally, GshF expression in mice is embryonically lethal but sustains postnatal viability when restricted to adulthood. Overall, our work identifies a conditional mouse model to investigate the limiting role of GSH in physiology and disease.


Assuntos
Glutamato-Cisteína Ligase , Glutationa , Animais , Camundongos , Butionina Sulfoximina/farmacologia , Modelos Animais de Doenças , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Glutationa/metabolismo , Linhagem Celular Tumoral , Humanos
6.
bioRxiv ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38260639

RESUMO

Glutathione (GSH) is a highly abundant tripeptide thiol that performs diverse protective and biosynthetic functions in cells. While changes in GSH availability are linked to many diseases, including cancer and neurodegenerative disorders, determining the function of GSH in physiology and disease has been challenging due to its tight regulation. To address this, we generated cell and mouse models that express a bifunctional glutathione-synthesizing enzyme from Streptococcus Thermophilus (GshF). GshF expression allows efficient production of GSH in the cytosol and mitochondria and prevents cell death in response to GSH depletion, but not ferroptosis, indicating that GSH is not a limiting factor under lipid peroxidation. CRISPR screens using engineered enzymes revealed metabolic liabilities under compartmentalized GSH depletion. Finally, GshF expression in mice is embryonically lethal but sustains postnatal viability when restricted to adulthood. Overall, our work identifies a conditional mouse model to investigate the role of GSH availability in physiology and disease.

7.
J Chromatogr Sci ; 62(3): 264-272, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36929845

RESUMO

Two rapid, smart and validated stability indicating HPLC and TLC techniques were developed to determine atenolol (ATE) and lercanidipine HCl (LER) simultaneously in their pharmaceutical formulation. HPLC chromatographic separation was implemented by using Microsorb C18 (250 × 4.6 mm, 5 µm) column, with mobile phase of acetonitrile and 20 mM potassium dihydrogen phosphate buffer pH 3.5 adjusted by orthophosphoric acid in the ratio of (65:35, v/v) at a flow rate of 1.2 mL/min at 240 nm also the injection volume adjusted to be 30 µL. These selected conditions effectively separated ATE and LER at a retention time of 2 and 6.7 min, respectively, by isocratic elution mode without any interference from the obtained degradation products of LER. The densitometric determination was performed by using precoated silica gel 60F254 aluminum plates and chloroform, methanol and triethylamine (11.3:1.3: 0.3, by volume) as a developing system. The detection wavelength for simultaneous estimation of both drugs was 240 nm in the presence of the oxidative product of LER. The RF values for ATE and LER were 0.22 and 0.78, respectively. The calibration curves of both techniques were constructed with linearity ranges of (5-55) µg.mL-1 and (1-55) µg.mL-1 for both ATE and LER, respectively, for HPLC determination. While for TLC, the linearity ranges were (1-4) µg/band and (0.2-1.4) µg/band for ATE and LER, respectively. LER degradation products were characterized using UPLC/MS and the suggested mechanisms and degradation pathways were introduced.


Assuntos
Atenolol , Di-Hidropiridinas , Cromatografia em Camada Fina/métodos , Reprodutibilidade dos Testes , Cromatografia Líquida de Alta Pressão/métodos
8.
bioRxiv ; 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37873082

RESUMO

Immunoglobulin A (IgA) is the most abundant antibody isotype produced across mammals and plays a specialized role in mucosal homeostasis 1 . Constantly secreted into the lumen of the intestine, IgA binds commensal microbiota to regulate their colonization and function 2,3 , with unclear implications for health. IgA deficiency is common in humans but is difficult to study due to its complex etiology and comorbidities 4-8 . Using genetically and environmentally controlled mice, here we show that IgA-deficient animals have a baseline alteration in the colon epithelium that increases susceptibility to multiple models of colorectal cancer. Transcriptome, imaging, and flow cytometry-based analyses revealed that, in the absence of IgA, colonic epithelial cells induce antibacterial factors and accelerate cell cycling in response to the microbiota. Oral treatment with IgA was sufficient to suppress aberrant epithelial proliferation independently of bacterial binding, suggesting that IgA provides a feedback signal to epithelial cells in parallel with its known roles in microbiome shaping. In a primary colonic organoid culture system, IgA directly suppresses epithelial growth. Conversely, the susceptibility of IgA-deficient mice to colorectal cancer was reversed by Notch inhibition to suppress the absorptive colonocyte developmental program, or by inhibition of the cytokine MIF, the receptor for which was upregulated in stem cells of IgA-deficient animals. These studies demonstrate a homeostatic function for IgA in tempering physiological epithelial responses to microbiota to maintain mucosal health.

9.
Int J Biol Macromol ; 250: 126067, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37524279

RESUMO

Silks are natural polymers that have been widely used for centuries. Silk consists of a filament core protein, termed fibroin, and a glue-like coating substance formed of sericin (SER) proteins. This protein is extracted from the silkworm cocoons (particularly Bombyx mori) and is mainly composed of amino acids like glycine, serine, aspartic acid, and threonine. Silk SER can be obtained using numerous methods, including enzymatic extraction, high-temperature, autoclaving, ethanol precipitation, cross-linking, and utilizing acidic, alkali, or neutral aqueous solutions. Given the versatility and outstanding properties of SER, it is widely fabricated to produce sponges, films, and hydrogels for further use in diverse biomedical applications. Hence, many authors reported that SER benefits cell proliferation, tissue engineering, and skin tissue restoration thanks to its moisturizing features, antioxidant and anti-inflammatory properties, and mitogenic effect on mammalian cells. Remarkably, SER is used in drug delivery depending on its chemical reactivity and pH-responsiveness. These unique features of SER enhance the bioactivity of drugs, facilitating the fabrication of biomedical materials at nano- and microscales, hydrogels, and conjugated molecules. This review thoroughly outlines the extraction techniques, biological properties, and respective biomedical applications of SER.

10.
J Fluoresc ; 33(4): 1609-1617, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36800042

RESUMO

An economical & eco-friendly spectrofluorometric method has been developed for the determination of prucalopride succinate (PRU) in human urine on the basis of the drug's native fluorescence. The type of solvent and the wavelengths of excitation and emission have been carefully selected for optimal experimental conditions. In deionized water, the fluorescence intensity was measured at λ emission 362 nm upon excitation at 310 nm. This bio-validated method was carried out using 30uL urine without any preliminary steps. The calibration curve for prucalopride succinate shows a linear relationship in a concentration range of 0.75-5.5 µg/mL. Accuracy and precision were obtained using 4 quality control samples which are: 0.75 µg/ mL (LLOQ), 2.25 µg/mL (QCL), 2.5 µg/mL (QCM) & 4.125 µg/mL (QCH). The validation of this proposed technique obeys European Medicines Agency (EMA) Guidelines for validating bioanalytical methods and the greenness assessment was evaluated according to the Analytical GAPI approach.


Assuntos
Benzofuranos , Humanos , Espectrometria de Fluorescência/métodos , Solventes , Succinatos
11.
Molecules ; 27(24)2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36558074

RESUMO

Degradation of the mycobacterial complex containing mycolic acids (MAs) by natural bioactive compounds is essential for producing safe and value-added foods with therapeutic activities. This study aimed to determine the degradation efficiency of natural organic acid extracts (i.e., citric, malic, tartaric, and lactic), quadri-mix extract from fruits and probiotics (i.e., lemon, apple, grape, and cell-free supernatant of Lactobacillus acidophilus), and synthetic pure organic acids (i.e., citric, malic, tartaric, and lactic), against MA in vitro in phosphate buffer solution (PBS) and Karish cheese models. The degradation effect was evaluated both individually and in combinations at different concentrations of degradants (1, 1.5, and 2%) and at various time intervals (0, 6, 12, 24, and 48 h). The results show that MA degradation percentage recorded its highest value at 2% of mixed fruit extract quadri-mix with L. acidophilus and reached 99.2% after 48 h both in PBS and Karish cheese, unlike other treatments (i.e., citric + malic + tartaric + lactic), individual acids, and sole extracts at all concentrations. Conversely, organic acid quadri-mix revealed the greatest MA degradation% of 95.9, 96.8, and 97.3% at 1, 1.5, and 2%, respectively, after 48 h. Citric acid was more effective in MA degradation than other acids. The fruit extract quadri-mix combined with L. acidophilus-fortified Karish cheese showed the highest sensorial characteristics; hence, it can be considered a novel food-grade degradant for MA and could be a promising biocontrol candidate against Mycobacterium tuberculosis (Mtb) in food matrices.


Assuntos
Queijo , Mycobacterium , Probióticos , Ácidos Micólicos , Queijo/microbiologia , Lactobacillus acidophilus , Ácidos/metabolismo , Probióticos/metabolismo
12.
Sci Rep ; 12(1): 13401, 2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927320

RESUMO

The current study aimed to figure out the effect of using a combination of 2% inulin, and 2% Fructo-oligosaccharides (FOS) with Lactobacillus acidophilus and their bacteriocin on some yogurt properties such as coagulation time, extending the shelf life of set yogurt and its microbiological quality, also the acceptance by consumers. The results indicated that coagulation time increased by 22.75% in yogurts prepared with Lactobacillus acidophilus and their bacteriocins compared to the control, and titratable acidity increased gradually in all treatments during storage. Hence control acidity (%) increased from 0.84 ± 0.02A at zero time to 1.23 ± 0.03A after 14 days of cold storage, while treatment (T4) was 0.72 ± 0.01C at zero time and reached 1.20 ± 0.5A after 39 days at the same conditions. The sensory properties showed the superiority of inulin, FOS, and Lactobacillus acidophilus bacteriocin groups. Lactobacillus bulgaricus, Streptococcus thermophiles, and Lactobacillus acidophilus count increased in the treatments compared to the control group, with an extended shelf life to 39 days of storage in the medicines containing lactobacillus acidophilus bacteriocin. Coliforms, Moulds, and yeasts did not detect in the treatments comprising 2% inulin, 2% FOS, and lactobacillus acidophilus bacteriocin for 39 days of refrigerated storage. This study proved that 2% inulin, 2% FOS, and Lactobacillus acidophilus bacteriocin fortification extended the shelf life by more than 5 weeks.


Assuntos
Bacteriocinas , Probióticos , Bacteriocinas/farmacologia , Inulina/farmacologia , Lactobacillus acidophilus , Oligossacarídeos/farmacologia , Probióticos/farmacologia , Iogurte/microbiologia
13.
Pan Afr Med J ; 41: 299, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35846869

RESUMO

Introduction: diabetic Ketoacidosis is the leading cause of mortality in children and adolescents with T1DM and accounts for about 50% of all deaths in patients younger than 24 years with diabetes. It affects 8 out of 1000 people with diabetes annually, with a worldwide mortality rate of 2-10%. The purpose of this study is to assess the knowledge and practice towards DKA among patients with diabetes attending three diabetes clinics in Khartoum. Methods: we conducted a cross-sectional institution-based study. It included all patients with diabetes attending three diabetes clinics in Khartoum state over the period July - September 2016. A self-administered questionnaire was used to assess and score knowledge and practice towards DKA among patients with diabetes. Data were analyzed using SPSS 23.0. Results: one hundred and ten patients participated in the study, of whom 86 had heard of DKA and were questioned further. Fifty-six point nine percent of participants had poor knowledge (0-8 out of 24) and low practice scores (0-2 out of 6). There was a strong association between knowledge scores and attended clinics. Conclusion: there was an evident lack of knowledge and poor practice towards DKA among patients with diabetes attending diabetes clinics in Khartoum, Sudan.


Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Adolescente , Instituições de Assistência Ambulatorial , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Humanos , Sudão
14.
Artigo em Inglês | MEDLINE | ID: mdl-35129085

RESUMO

The aim of this study was to enhance the rhizobacterium potential in horizontal subsurface flow constructed wetland (CW) system planted by Phragmites australis using specific and lytic phages. The bioinoculation of specific bacteriophage for target bacteria; Salmonella typhi, and the monitoring of bacterial inactivation under different conditions showed the effectiveness of this methodology to enhance bacteria reduction and consequentially ameliorate purification performance of this studied biological treatment system. The injection of the phage at a concentration equal to 103 UFP/mL within the rhizosphere of the inoculated filter (F) was allowed 1 U-Log10 of improvement of bacterial inactivation compared to the control filter (T) nearly 1 logarithmic unit thus, a 90% improvement of bacteria reduction. When we increased the phage titer (105 UFP/mL), the bacterial reduction equal to 2.75 U-Log10 (N/N0) was registered that corresponds to a decrease of nearly 99.9%. According to the first-order model, the inactivation coefficient is equal to 2.29 min-1 (0.88 min-1 for the first experiment) and the bacterial reduction rate is 5 times higher than that determined for the control filter. This results show the positive impact of the phage in the bacterial inactivation and the improvement of water treatment of the biofilter C.


Assuntos
Bacteriófagos , Purificação da Água , Bactérias , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/microbiologia , Purificação da Água/métodos , Áreas Alagadas
15.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35042816

RESUMO

HIV-1 infection produces a long-lived reservoir of latently infected CD4+ T cells that represents the major barrier to HIV-1 cure. The reservoir contains both intact and defective proviruses, but only the proviruses that are intact can reinitiate infection upon cessation of antiretroviral therapy (ART). Here we combine four-color quantitative PCR and next-generation sequencing (Q4PCR) to distinguish intact and defective proviruses and measure reservoir content longitudinally in 12 infected individuals. Q4PCR differs from other PCR-based methods in that the amplified proviruses are sequence verified as intact or defective. Samples were collected systematically over the course of up to 10 y beginning shortly after the initiation of ART. The size of the defective reservoir was relatively stable with minimal decay during the 10-y observation period. In contrast, the intact proviral reservoir decayed with an estimated half-life of 4.9 y. Nevertheless, both intact and defective proviral reservoirs are dynamic. As a result, the fraction of intact proviruses found in expanded clones of CD4+ T cells increases over time with a concomitant decrease in overall reservoir complexity. Thus, reservoir decay measurements by Q4PCR are quantitatively similar to viral outgrowth assay (VOA) and intact proviral DNA PCR assay (IPDA) with the addition of sequence information that distinguishes intact and defective proviruses and informs reservoir dynamics. The data are consistent with the notion that intact and defective proviruses are under distinct selective pressure, and that the intact proviral reservoir is progressively enriched in expanded clones of CD4+ T cells resulting in diminishing complexity over time.


Assuntos
HIV-1/patogenicidade , Latência Viral/genética , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Sequência de Bases/genética , Linfócitos T CD4-Positivos/virologia , DNA Viral/genética , Infecções por HIV/virologia , Soropositividade para HIV , HIV-1/genética , HIV-1/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Provírus/genética , Análise de Sequência de DNA/métodos , Carga Viral , Latência Viral/fisiologia
16.
Saudi J Kidney Dis Transpl ; 33(2): 288-295, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37417181

RESUMO

Chronic kidney disease (CKD) and dementia are common morbidities of elders. Serum cystatin C has been suggested to be an ideal marker for kidney function. The current study aimed to detect the serum levels of cystatin C in CKD patients and to correlate these levels to cognitive performance. The study involved 90 subjects aged 65 years and more, divided into two groups: Group 1: 60 patients with CKD, and Group 2: 30 control participants. Exclusion criteria included cardiac failure, hepatic failure, thyroid diseases, dialysis for more than one month, polycystic kidney disease, organ transplantation, and immunosuppressive therapy within the past six months. All participants had routine laboratory workup, serum cystatin C using enzyme-linked immunosorbent assay kits, and cognitive assessment using mini-mental state examination (MMSE). Serum cystatin level was significantly high in CKD patients while MMSE scores were significantly lower in CKD patients. A high significant negative correlation was found between serum cystatin C levels and both degree of cognitive impairment and glomerular filtration rate (GFR). Also, a significant positive correlation was found between the degree of cognitive impairment and GFR levels. Serum cystatin levels are significantly associated with cognitive impairment in CKD patients, and this correlation becomes more evident with the worsening of CKD stages. That may help in better understanding of the pathogenesis of dementia in CKD patients with the emergence of therapeutic options depending on these data.


Assuntos
Demência , Insuficiência Renal Crônica , Idoso , Humanos , Cistatina C , Egito/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Taxa de Filtração Glomerular , Cognição , Creatinina , Biomarcadores
18.
Biosensors (Basel) ; 11(12)2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34940275

RESUMO

Exosomes, powerful extracellular nanovesicles released from almost all types of living cells, are considered the communication engines (messengers) that control and reprogram physiological pathways inside target cells within a community or between different communities. The cell-like structure of these extracellular vesicles provides a protective environment for their proteins and DNA/RNA cargos, which serve as biomarkers for many malicious diseases, including infectious diseases and cancers. Cancer-derived exosomes control cancer metastasis, prognosis, and development. In addition to the unique structure of exosomes, their nanometer size and tendency of interacting with cells makes them a viable novel drug delivery solution. In recent years, numerous research efforts have been made to quantify and characterize disease-derived exosomes for diagnosis, monitoring, and therapeutic purposes. This review aims to (1) relate exosome biomarkers to their origins, (2) focus on current isolation and detection methods, (3) discuss and evaluate the proposed technologies deriving from exosome research for cancer treatment, and (4) form a conclusion about the prospects of the current exosome research.


Assuntos
Exossomos , Neoplasias , Biomarcadores , Comunicação Celular , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias/diagnóstico , Proteínas
20.
Antibiotics (Basel) ; 10(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34439071

RESUMO

This study aims to determine the prevalence of STEC in she-camels suffering from mastitis in semi-arid regions by using traditional culture methods and then confirming it with Serological and molecular techniques in milk samples, camel feces, as well as human stool samples for human contacts. In addition, an antibiotic susceptibility profile for these isolates was investigation. Mastitic milk samples were taken after California Mastitis Test (CMT) procedure, and fecal samples were taken from she-camels and human stool samples, then cultured using traditional methods to isolate Escherichiacoli. These isolates were initially classified serologically, then an mPCR (Multiplex PCR) was used to determine virulence genes. Finally, both camel and human isolates were tested for antibiotic susceptibility. Out of a total of 180 she-camels, 34 (18.9%) were mastitic (8.3% clinical and 10.6% sub-clinical mastitis), where it was higher in camels bred with other animals. The total presence of E. coli was 21.9, 13.9, and 33.7% in milk, camel feces, and human stool, respectively, whereas the occurrence of STEC from the total E. coli isolates were 36, 16, and 31.4% for milk, camel feces, and stool, respectively. Among the camel isolates, stx1 was the most frequently detected virulence gene, while hlyA was not detected. The most detected virulence gene in human isolates was stx2 (45.5%), followed by stx1. Camel STEC showed resistance to Oxytetracycline only, while human STEC showed multiple drug resistance to Amoxicillin, Gentamycin, and Clindamycin with 81.8, 72.7, and 63.6%, respectively. Breeding camels in semi-arid areas separately from other animals may reduce the risk of infection with some bacteria, including E. coli; in contrast, mixed breeding with other animals contributes a significant risk factor for STEC emergence in camels.

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