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1.
Sci Rep ; 14(1): 10239, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702340

RESUMEN

The classification of locally rotationally symmetric Bianchi type V spacetime based on its killing vector fields is presented in this paper using an algebraic method. In this approach, a Maple algorithm is employed to transform the Killing's equations into a reduced evolutive form. Subsequently, the integration of the Killing's equations is carried out subject to the constraints provided by the algorithm. The algorithm demonstrates that there exist fifteen distinct metrics that could potentially possess Killing vector fields. Upon solving the Killing equations for all fifteen metrics, it is observed that seven out of the fifteen metrics exclusively exhibit the minimum number of Killing vector fields. The remaining eight metrics admit a varying number of Killing vector fields, specifically 6, 7, or 10. The Kretschmann scalar has been computed for each of the obtained metrics, revealing that all of them possess a finite Kretschmann scalar and thus exhibit regular behavior.

2.
bioRxiv ; 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38405843

RESUMEN

Plasmodium parasites, which are the causative agents of malaria, undergo closed mitosis without breakdown of the nuclear envelope. Unlike the closed mitosis in yeast, P. berghei parasites undergo multiple rounds of asynchronous nuclear divisions in a shared cytoplasm result in a multinucleated (8-24) organism prior to formation of daughter cells within an infected red blood cell. During this replication process, intact nuclear pore complexes (NPCs) and their component nucleoporins are likely to play critical roles in parasite growth, facilitating selective bi-directional nucleocytoplasmic transport and genome organization. Here we utilize ultrastructure expansion microscopy (U-ExM) to investigate P. berghei Nup138, Nup221, and Nup313 at the single nucleus level throughout the 24 hour blood-stage replication cycle. Our findings reveal that these Nups are evenly distributed around the nuclei and organized in a rosette structure previously undescribed around the centriolar plaque, which is responsible for intranuclear microtubule nucleation during mitosis. We also detect an increased number of NPCs compared with previously reported, highlighting the power of U-ExM. By adapting the recombination-induced tag exchange (RITE) system to P. berghei, we provide evidence of NPC maintenance, demonstrating Nup221 turnover during parasite asexual replication. Our data shed light on the distribution of NPCs and their homeostasis during the blood-stage replication of P. berghei parasites. Further studies into the nuclear surface of these parasites will allow for a better understanding of parasites nuclear mechanics and organization.

3.
J Biomol Struct Dyn ; 42(5): 2231-2241, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37116071

RESUMEN

For more than a century, the renin-angiotensin system (RAS) has been acknowledged for playing a crucial part in the physiological control of arterial pressure, as well as sodium and fluid balance. It is now generally acknowledged that one of the receptor of RAS system i.e. angiotensin type 2 receptor (AT2R) functions as a repair system during pathophysiologic circumstances and performs a significant protective role. Efforts have been made previously to design suitable agonist and antagonist molecules to potentially modulate AT2R. One of the agonists and antagonists, named C21 and EMA401, has been studied in a number of pathological conditions. Additionally, a wide panel of single nucleotide polymorphisms (SNPs) has been reported for AT2R, which might potentially affect the efficacy of these molecules. Therefore, computational investigations have been carried out to analyze all the SNPs (1151) reported in NCBI to find potential SNPs affecting the active site of AT2R, as this domain is still unexplored. Structures of these polymorphic forms were modeled, and in silico drug interaction studies with C21 and EMA401 were carried out. The two mutants (rs868939201 and rs1042852794) that significantly affect the binding affinity as that of the wild type were subjected to molecular dynamics simulations. Our analysis of native and mutant AT2R and their complexes with C21 and EMA401 indicated that the occurrence of these mutations affects the conformation of the protein and has affected the binding of these ligand molecules. The study's findings will aid in the development of better, more versatile medications in the near future, and also in vitro and in vivo studies might be planned in accordance with recent findings.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Compuestos de Bencidrilo , Imidazoles , Isoquinolinas , Sistema Renina-Angiotensina , Sulfonamidas , Tiofenos , Receptor de Angiotensina Tipo 2/agonistas , Receptor de Angiotensina Tipo 2/genética , Receptor de Angiotensina Tipo 2/metabolismo
4.
BMC Complement Med Ther ; 23(1): 349, 2023 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-37789322

RESUMEN

BACKGROUND: Zingiber officinale, generally known as ginger, contains bioactive phytochemicals, including gingerols and shogaols, that may function as reducing agents and stabilizers for the formation of nickel nanoparticles (Ni-NPs). Ginger extract-mediated nickel nanoparticles were synthesized using an eco-friendly method, and their antibacterial, antioxidant, antiparasitic, antidiabetic, anticancer, dye degrading, and biocompatibility properties were investigated. METHODS: UV-visible spectroscopy, fourier transform infrared spectroscopy, X-ray powder diffraction, energy-dispersive X-ray spectroscopy, and scanning electron microscopy were used to validate and characterize the synthesis of Ni-NPs. Agar well diffusion assay, alpha-amylase and glucosidase inhibitory assay, free radical scavenging assay, biocompatibility assay, and MTT assay were used to analyse the biomedical importance of Ni-NPs. RESULTS: SEM micrograph examinations revealed almost aggregates of Ni-NPs; certain particles were monodispersed and spherical, with an average grain size of 74.85 ± 2.5 nm. Ni-NPs have successfully inhibited the growth of Pseudomonas aeruginosa, Escherichia coli, and Proteus vulgaris by inducing membrane damage, as shown by the absorbance at 260 nm (A260). DPPH (2,2-diphenyl-1-picrylhydrazyl) free radicals were successfully scavenged by Ni-NPs at an inhibition rate of 69.35 ± 0.81% at 800 µg/mL. A dose-dependent cytotoxicity of Ni-NPs was observed against amastigote and promastigote forms of Leishmania tropica, with significant mortality rates of 94.23 ± 1.10 and 92.27 ± 1.20% at 1.0 mg/mL, respectively. Biocompatibility studies revealed the biosafe nature of Ni-NPs by showing RBC hemolysis up to 1.53 ± 0.81% at 400 µg/mL, which is considered safe according to the American Society for Materials and Testing (ASTM). Furthermore, Ni-NPs showed antidiabetic activity by inhibiting α-amylase and α-glucosidase enzymes at an inhibition rate of 22.70 ± 0.16% and 31.23 ± 0.64% at 200 µg/mL, respectively. Ni-NPs have shown significant cytotoxic activity by inhibiting MCF-7 cancerous cells up to 68.82 ± 1.82% at a concentration of 400 µg/mL. The IC50 for Ni-NPs was almost 190 µg/mL. Ni-NPs also degraded crystal violet dye up to 86.1% at 2 h of exposure. CONCLUSIONS: In conclusion, Zingiber officinale extract was found successful in producing stable nanoparticles. Ni-NPs have shown substantial biomedical activities, and as a result, we believe these nanoparticles have potential as a powerful therapeutic agent for use in nanomedicine.


Asunto(s)
Nanopartículas del Metal , Zingiber officinale , Níquel , Rizoma , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Hipoglucemiantes/farmacología , alfa-Amilasas
5.
Am J Physiol Renal Physiol ; 325(5): F552-F563, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37615049

RESUMEN

Lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is characterized by inflammation and infiltration of immune cells, mainly neutrophils and macrophages, and results in sudden renal dysfunction. Previously, we have reported the anti-inflammatory and renoprotective role of the angiotensin II type 2 receptor (AT2R), expressed on kidney tubular cells and immune cells, in LPS-induced AKI. Moreover, in vitro studies revealed macrophage AT2R activation shifts the cells to the anti-inflammatory M2 subtype. However, the protective role of the macrophage AT2R in a model of AKI is unknown. The present study addressed this question by adoptive transfer of bone marrow-derived macrophages (BMDMs) in systemic macrophage-depleted mice. We acquired significant systemic macrophage depletion by two doses of liposomal clodronate (CLD), and the mice were repopulated with BMDMs (CD11b+F4/80+, double positive) primed with AT2R agonist C21 (CLD + MacC21 + LPS) or vehicle (CLD + Mac + LPS) in vitro for 60 min, followed by LPS (5 mg/kg body wt ip) challenge. We observed a gradual increase in the CD11b+ cells at 2 and 24 h after the LPS challenge. However, kidney CD11b+ cells in the CLD + Mac + LPS group were elevated compared with the CLD + MacC21 + LPS group at 2 h after the LPS challenge. The level of inflammatory cytokine (tumor necrosis factor-α) was elevated at 2 h, which was reduced significantly in CLD + MacC21 + LPS-treated animals. Also, CLD + MacC21 + LPS-treated animals had elevated plasma and renal IL-10, indicating an anti-inflammatory role of C21-treated BMDMs. Renal functional injury in CLD + MacC21 + LPS-treated animals was partially improved. Collectively, the data demonstrate that BMDM AT2R stimulation results in anti-inflammation and partial renoprotection against early stages of LPS-induced AKI.NEW & NOTEWORTHY Endotoxin such as lipopolysaccharide (LPS) induces acute kidney injury (AKI), which is a risk factor for and often leads to chronic kidney diseases. The present study revealed that bone marrow-derived macrophage activation of the angiotensin II type 2 receptor (AT2R) contributes to the anti-inflammation and partial renoprotection against early stages of LPS-induced AKI. Since AT2R is an emerging anti-inflammatory and organ-protective target, this study advances our understanding of AT2R's anti-inflammatory mechanisms associated with renoprotection.


Asunto(s)
Lesión Renal Aguda , Lipopolisacáridos , Ratones , Animales , Lipopolisacáridos/toxicidad , Receptor de Angiotensina Tipo 2 , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Macrófagos/patología , Antiinflamatorios/farmacología , Angiotensinas , Ratones Endogámicos C57BL
6.
Proc Natl Acad Sci U S A ; 120(33): e2308676120, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37552754

RESUMEN

Malaria parasites uniquely depend on protein secretion for their obligate intracellular lifestyle but approaches for dissecting Plasmodium-secreted protein functions are limited. We report knockER, a unique DiCre-mediated knock-sideways approach to sequester secreted proteins in the ER by inducible fusion with a KDEL ER-retrieval sequence. We show conditional ER sequestration of diverse proteins is not generally toxic, enabling loss-of-function studies. We employed knockER in multiple Plasmodium species to interrogate the trafficking, topology, and function of an assortment of proteins that traverse the secretory pathway to diverse compartments including the apicoplast (ClpB1), rhoptries (RON6), dense granules, and parasitophorous vacuole (EXP2, PTEX150, HSP101). Taking advantage of the unique ability to redistribute secreted proteins from their terminal destination to the ER, we reveal that vacuolar levels of the PTEX translocon component HSP101 but not PTEX150 are maintained in excess of what is required to sustain effector protein export into the erythrocyte. Intriguingly, vacuole depletion of HSP101 hypersensitized parasites to a destabilization tag that inhibits HSP101-PTEX complex formation but not to translational knockdown of the entire HSP101 pool, illustrating how redistribution of a target protein by knockER can be used to query function in a compartment-specific manner. Collectively, our results establish knockER as a unique tool for dissecting secreted protein function with subcompartmental resolution that should be widely amenable to genetically tractable eukaryotes.


Asunto(s)
Plasmodium falciparum , Plasmodium , Plasmodium falciparum/metabolismo , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Plasmodium/metabolismo , Transporte de Proteínas , Transporte Biológico , Eritrocitos/metabolismo
7.
Waste Manag ; 170: 112-121, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37572447

RESUMEN

The volatiles and char derived from municipal solid waste (MSW) pyrolysis can be catalytically reformed and gasified using high-temperature CO2 (HT-CO2) as gasifying agent and char as a catalyst simultaneously to obtain high quality synthesis gas, but the reactor's design for this purpose is still a question. In this research, the contact configuration between the HT-CO2, the volatile compounds, and the char from MSW pyrolysis were studied to understand the relevant reaction behaviors and to establish guidelines for the reactor's design. Three contact modes were designed, including: M1, where volatiles and HT-CO2 contact first, then contact the char; M2, where volatiles, CO2, and char contact simultaneously at the bottom of the char layer; and M3, where CO2 contacts with the char first, then the volatiles contact in the middle of the char layer. The temperature evolution in the char layer, the yields and properties of the resultant combustible gases, used char, and tar were investigated. Experimental results revealed that the contact mode significantly affected the levels of char gasification and volatiles' reforming. For M1, intense thermal cracking of volatiles occurred and 65.41% of the input heat of HT-CO2 was consumed for thermal cracking, resulting in substantial carbon deposition and limited energy transfer from char to the synthesis gas. While, the char contacting HT-CO2 firstly in M3 improved its catalytic activity, causing 73.33 % of the input heat utilized for gasification and reforming; as a result, the maximum synthesis gas yield of 0.71 Nm3/kgMSW and gas energy ratio of 76.3 % were obtained respectively in M3 with the lowest tar yield of 5.45 %; additionally, the used char corresponded to the highest specific surface area of 10.12 m2/g. Ultimately, M3 is constructive and recommended, and the findings of this study offer helpful guidance for the design of pyro-gasification reactors.

8.
Molecules ; 28(14)2023 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-37513425

RESUMEN

The significance of nanomaterials in biomedicines served as the inspiration for the design of this study. In this particular investigation, we carried out the biosynthesis of calcium oxide nanoparticles (CaONPs) by employing a green-chemistry strategy and making use of an extract of Ficus carica (an edible fruit) as a capping and reducing agent. There is a dire need for new antimicrobial agents due to the alarming rise in antibiotic resistance. Nanoparticles' diverse antibacterial properties suggest that they might be standard alternatives to antimicrobial drugs in the future. We describe herein the use of a Ficus carica extract as a capping and reducing agent in the phyto-mediated synthesis of CaONPs for the evaluation of their antimicrobial properties. The phyto-mediated synthesis of NPs is considered a reliable approach due to its high yield, stability, non-toxicity, cost-effectiveness and eco-friendliness. The CaONPs were physiochemically characterized by UV-visible spectroscopy, energy-dispersive X-ray (EDX), scanning-electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). The biological synthesis of the calcium oxide nanoparticles revealed a characteristic surface plasmon resonance peak (SPR) at 360 nm in UV-Vis spectroscopy, which clearly revealed the successful reduction of the Ca2+ ions to Ca0 nanoparticles. The characteristic FTIR peak seen at 767 cm-1 corresponded to Ca-O bond stretching and, thus, confirmed the biosynthesis of the CaONPs, while the scanning-electron micrographs revealed near-CaO aggregates with an average diameter of 84.87 ± 2.0 nm. The antibacterial and anti-biofilm analysis of the CaONPs showed inhibition of bacteria in the following order: P. aeruginosa (28 ± 1.0) > S. aureus (23 ± 0.3) > K. pneumoniae (18 ± 0.9) > P. vulgaris (13 ± 1.6) > E. coli (11 ± 0.5) mm. The CaONPs were shown to considerably inhibit biofilm formation, providing strong evidence for their major antibacterial activity. It is concluded that this straightforward environmentally friendly method is capable of synthesizing stable and effective CaONPs. The therapeutic value of CaONPs is indicated by their potential as a antibacterial and antibiofilm agents in future medications.


Asunto(s)
Antiinfecciosos , Ficus , Nanopartículas del Metal , Staphylococcus aureus , Sustancias Reductoras/farmacología , Escherichia coli , Nanopartículas del Metal/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antibacterianos/farmacología , Antibacterianos/química , Antiinfecciosos/farmacología , Biopelículas , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X , Pruebas de Sensibilidad Microbiana
9.
Antibiotics (Basel) ; 12(4)2023 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-37107035

RESUMEN

Staphylococcus aureus is a prominent cause of food-borne diseases worldwide. Enterotoxigenic strains of this bacteria are frequently found in raw milk, and some of these strains are resistant to antimicrobials, posing a risk to consumers. The main objectives of this study were to determine the antimicrobial resistance pattern of S. aureus in raw milk and to detect the presence of mecA and tetK genes in it. A total of 150 milk samples were obtained aseptically from lactating cattle, including Holstein Friesian, Achai, and Jersey breeds, maintained at different dairy farms. The milk samples were checked for the presence of S. aureus, and it was detected in 55 (37%) of them. The presence of S. aureus was verified by culturing on selective media, gram staining, and performing coagulase and catalase tests. Further confirmation was performed through PCR with a species-specific thermonuclease (nuc) gene. Antimicrobial susceptibility testing of the confirmed S. aureus was then determined by using the Kirby-Bauer disc diffusion technique. Out of the 55 confirmed S. aureus isolates, 11 were determined to be multidrug-resistant (MDR). The highest resistance was found to penicillin (100%) and oxacillin (100%), followed by tetracycline (72.72%), amikacin (27.27%), sulfamethoxazole/trimethoprim (18.18%), tobramycin (18.18%), and gentamycin (9.09%). Amoxicillin and ciprofloxacin were found to be susceptible (100%). Out of 11 MDR S. aureus isolates, the methicillin resistance gene (mecA) was detected in 9 isolates, while the tetracycline resistance gene (tetK) was found in 7 isolates. The presence of these methicillin- and tetracycline-resistant strains in raw milk poses a major risk to public health, as they can cause food poisoning outbreaks that can spread rapidly through populations. Our study concludes that out of nine empirically used antibiotics, amoxicillin, ciprofloxacin, and gentamicin were highly effective against S. aureus compared to penicillin, oxacillin, and tetracycline.

10.
Sci Rep ; 13(1): 4277, 2023 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-36922642

RESUMEN

Proteinuria is a risk factor for and consequence of kidney injury. Angiotensin II type 2 receptor (AT2R) is an emerging reno-protective target and is anti-proteinuric under pathological conditions, including high salt-fed obese animals. However, the mechanisms remain unknown, particularly whether the anti-proteinuric activity of AT2R is independent of its anti-hypertensive and anti-inflammatory effects. In the present study, obese Zucker rats were fed high sodium (4%) diet (HSD) for 48 h, a time in which blood pressure does not change. HSD caused proteinuria without affecting glomerular slit diaphragm proteins (nephrin and podocin), glomerular filtration rate, inflammatory and fibrotic markers (TNFα, IL-6, and TGF-ß), ruling out glomerular injury, inflammation and fibrosis but indicating tubular mechanisms of proteinuria. At cellular and molecular levels, we observed a glycogen synthase kinase (GSK)-3ß-mediated megalin phosphorylation, and its subsequent endocytosis and lysosomal degradation in HSD-fed rat kidneys. Megalin is a major proximal tubular endocytic protein transporter. The AT2R agonist C21 (0.3 mg/kg/day, i.p.) administration prevented proteinuria and rescued megalin surface expression potentially by activating Akt-mediated phosphorylation and inactivation of GSK-3ß in HSD-fed rat kidneys. Overall, AT2R has a direct anti-proteinuric activity, potentially via megalin regulation, and is suggested as a novel target to limit kidney injury.


Asunto(s)
Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad , Proteinuria , Receptor de Angiotensina Tipo 2 , Animales , Ratas , Dieta , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glomérulos Renales/patología , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Obesidad/metabolismo , Proteinuria/metabolismo , Ratas Zucker , Receptor de Angiotensina Tipo 1/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Cloruro de Sodio Dietético/farmacología
11.
mBio ; 13(6): e0309622, 2022 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-36445080

RESUMEN

During vertebrate infection, obligate intracellular malaria parasites develop within a parasitophorous vacuole, which constitutes the interface between the parasite and its hepatocyte or erythrocyte host cells. To traverse this barrier, Plasmodium spp. utilize a dual-function pore formed by EXP2 for nutrient transport and, in the context of the PTEX translocon, effector protein export across the vacuole membrane. While critical to blood-stage survival, less is known about EXP2/PTEX function in the liver stage, although major differences in the export mechanism are suggested by absence of the PTEX unfoldase HSP101 in the intrahepatic vacuole. Here, we employed the glucosamine-activated glmS ribozyme to study the role of EXP2 during Plasmodium berghei liver-stage development in hepatoma cells. Insertion of the glmS sequence into the exp2 3' untranslated region (UTR) enabled glucosamine-dependent depletion of EXP2 after hepatocyte invasion, allowing separation of EXP2 function during intrahepatic development from a recently reported role in hepatocyte invasion. Postinvasion EXP2 knockdown reduced parasite size and largely abolished expression of the mid- to late-liver-stage marker LISP2. As an orthogonal approach to monitor development, EXP2-glmS parasites and controls were engineered to express nanoluciferase. Activation of glmS after invasion substantially decreased luminescence in hepatoma monolayers and in culture supernatants at later time points corresponding to merosome detachment, which marks the culmination of liver-stage development. Collectively, our findings extend the utility of the glmS ribozyme to study protein function in the liver stage and reveal that EXP2 is important for intrahepatic parasite development, indicating that PTEX components also function at the hepatocyte-parasite interface. IMPORTANCE After the mosquito bite that initiates a Plasmodium infection, parasites first travel to the liver and develop in hepatocytes. This liver stage is asymptomatic but necessary for the parasite to transition to the merozoite form, which infects red blood cells and causes malaria. To take over their host cells, avoid immune defenses, and fuel their growth, these obligately intracellular parasites must import nutrients and export effector proteins across a vacuole membrane in which they reside. In the blood stage, these processes depend on a translocon called PTEX, but it is unclear if PTEX also functions during the liver stage. Here, we adapted the glmS ribozyme to control expression of EXP2, the membrane pore component of PTEX, during the liver stage of the rodent malaria parasite Plasmodium berghei. Our results show that EXP2 is important for intracellular development in the hepatocyte, revealing that PTEX components are also functionally important during liver-stage infection.


Asunto(s)
Eritrocitos , Hepatocitos , Malaria , Plasmodium berghei , Proteínas Protozoarias , Carcinoma Hepatocelular , Eritrocitos/metabolismo , Eritrocitos/parasitología , Neoplasias Hepáticas , Malaria/genética , Malaria/metabolismo , Malaria/parasitología , Plasmodium berghei/genética , Plasmodium berghei/metabolismo , Plasmodium falciparum/genética , Transporte de Proteínas/genética , Transporte de Proteínas/fisiología , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , ARN Catalítico/metabolismo , Animales , Ratones , Hepatocitos/metabolismo , Hepatocitos/parasitología
12.
Clin Sci (Lond) ; 136(20): 1467-1470, 2022 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-36287192

RESUMEN

Podocyte injury due to either drug, toxin, infection, or metabolic abnormality is a great concern as it increases the risk of developing focal segmental glomerulosclerosis (FSGS) and proteinuric kidney diseases. The direct podocyte injury due to doxorubicin is associated with an increase in proinflammatory cytokines and induction of cathepsin L. The increased activity of cathepsin L in turn may degrade the glomerular slit diaphragm resulting in proteinuric kidney injury. The angiotensin-II type 2 receptor (AT2R) has earlier been reported to be associated with the preservation of slit diaphragm proteins and prevention of proteinuria. Recent in vivo findings by Zhang and colleagues further support the anti-proteinuric role of AT2R in preventing podocyte injury via down-regulating cytokines ccl2, and hence, cathepsin L, thereby, limiting the progression of FSGS.


Asunto(s)
Glomeruloesclerosis Focal y Segmentaria , Enfermedades Renales , Podocitos , Humanos , Glomeruloesclerosis Focal y Segmentaria/prevención & control , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Catepsina L/metabolismo , Catepsina L/uso terapéutico , Glomérulos Renales/metabolismo , Podocitos/metabolismo , Proteinuria/metabolismo , Enfermedades Renales/metabolismo , Doxorrubicina , Angiotensinas/metabolismo
13.
J Pak Med Assoc ; 72(8): 1626-1628, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36280931

RESUMEN

Basilic vein transposition (BVT) is the preferred permanent haemodialysis access due to better patency and lower infection rates compared to synthetic grafts. The outcomes of BVT cases, performed at Shifa International Hospital, Islamabad, from March 2006 to June 2018, were ambispectively investigated. The primary patency of the fistula was assessed immediately after surgery, at 24 hours, at 7-14 days, at 6-8 weeks and then at 3-6 months. A total of 160 patients were included in the study, out of which 83 (51.87%) were males while 77 (48.12%) were females. Of the total 160 patients, 119 (74.4%) underwent one stage BVT, while 41 (25.6%) underwent two stage BVT. One hundred and thirty-five (84.4%) procedures were successful and survived while in 25 (15.6%) cases it failed. Mean basilic vein diameter was 2.712±0.772 mm. Overall, 10(6.3%) patients had bleeding, 15(9.4%) fistulae thrombosed, 6(3.8%) had steal syndrome and only 1 (0.6%) patient developed pseudo aneurysm. We conclude that BVT is a feasible technique with very good patency rate especially for those patients who have multiple forearm AVF surgeries.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Masculino , Femenino , Humanos , Derivación Arteriovenosa Quirúrgica/métodos , Grado de Desobstrucción Vascular , Venas/cirugía , Centros de Atención Terciaria , Resultado del Tratamiento , Estudios Retrospectivos , Diálisis Renal/métodos
14.
Pharmacol Rev ; 74(4): 1051-1135, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36180112

RESUMEN

Discovered more than 30 years ago, the angiotensin AT2 receptor (AT2R) has evolved from a binding site with unknown function to a firmly established major effector within the protective arm of the renin-angiotensin system (RAS) and a target for new drugs in development. The AT2R represents an endogenous protective mechanism that can be manipulated in the majority of preclinical models to alleviate lung, renal, cardiovascular, metabolic, cutaneous, and neural diseases as well as cancer. This article is a comprehensive review summarizing our current knowledge of the AT2R, from its discovery to its position within the RAS and its overall functions. This is followed by an in-depth look at the characteristics of the AT2R, including its structure, intracellular signaling, homo- and heterodimerization, and expression. AT2R-selective ligands, from endogenous peptides to synthetic peptides and nonpeptide molecules that are used as research tools, are discussed. Finally, we summarize the known physiological roles of the AT2R and its abundant protective effects in multiple experimental disease models and expound on AT2R ligands that are undergoing development for clinical use. The present review highlights the controversial aspects and gaps in our knowledge of this receptor and illuminates future perspectives for AT2R research. SIGNIFICANCE STATEMENT: The angiotensin AT2 receptor (AT2R) is now regarded as a fully functional and important component of the renin-angiotensin system, with the potential of exerting protective actions in a variety of diseases. This review provides an in-depth view of the AT2R, which has progressed from being an enigma to becoming a therapeutic target.


Asunto(s)
Receptor de Angiotensina Tipo 2 , Sistema Renina-Angiotensina , Angiotensinas/metabolismo , Angiotensinas/farmacología , Sitios de Unión , Humanos , Ligandos , Péptidos/química , Péptidos/metabolismo , Péptidos/farmacología , Receptor de Angiotensina Tipo 1/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo
15.
J Pak Med Assoc ; 72(2): 360-362, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35320194

RESUMEN

Extra-cranial arteriovenous malformations of head and neck are rare and may present with acute haemorrhage. Their management varies and requires a multidisciplinary approach. Intra-arterial embolisation alone or followed by surgery is recommended. We present here a case of a huge pulsatile lesion extending from the neck to the temporo-parietal region with the main feeding vessel being the right external carotid artery. It was treated with surgical resection only as the feeding artery was very tortuous making selective embolization of artery impossible. The excision of the portion of the artery in the neck was carried out a week later. The patient recovered smoothly except for transient facial nerve palsy.


Asunto(s)
Malformaciones Arteriovenosas , Embolización Terapéutica , Malformaciones Arteriovenosas/complicaciones , Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/terapia , Cabeza/diagnóstico por imagen , Cabeza/patología , Humanos , Cuello/diagnóstico por imagen , Cráneo
16.
Comput Math Methods Med ; 2022: 5137513, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35190751

RESUMEN

Internet of Things (IoT) with deep learning (DL) is drastically growing and plays a significant role in many applications, including medical and healthcare systems. It can help users in this field get an advantage in terms of enhanced touchless authentication, especially in spreading infectious diseases like coronavirus disease 2019 (COVID-19). Even though there is a number of available security systems, they suffer from one or more of issues, such as identity fraud, loss of keys and passwords, or spreading diseases through touch authentication tools. To overcome these issues, IoT-based intelligent control medical authentication systems using DL models are proposed to enhance the security factor of medical and healthcare places effectively. This work applies IoT with DL models to recognize human faces for authentication in smart control medical systems. We use Raspberry Pi (RPi) because it has low cost and acts as the main controller in this system. The installation of a smart control system using general-purpose input/output (GPIO) pins of RPi also enhanced the antitheft for smart locks, and the RPi is connected to smart doors. For user authentication, a camera module is used to capture the face image and compare them with database images for getting access. The proposed approach performs face detection using the Haar cascade techniques, while for face recognition, the system comprises the following steps. The first step is the facial feature extraction step, which is done using the pretrained CNN models (ResNet-50 and VGG-16) along with linear binary pattern histogram (LBPH) algorithm. The second step is the classification step which can be done using a support vector machine (SVM) classifier. Only classified face as genuine leads to unlock the door; otherwise, the door is locked, and the system sends a notification email to the home/medical place with detected face images and stores the detected person name and time information on the SQL database. The comparative study of this work shows that the approach achieved 99.56% accuracy compared with some different related methods.


Asunto(s)
Reconocimiento Facial Automatizado , Aprendizaje Profundo , Internet de las Cosas , Algoritmos , COVID-19 , Seguridad Computacional , Simulación por Computador , Bases de Datos Factuales , Diseño de Equipo , Humanos , Reconocimiento de Normas Patrones Automatizadas , SARS-CoV-2 , Máquina de Vectores de Soporte
17.
Saudi J Biol Sci ; 29(1): 411-419, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35002436

RESUMEN

In recent years green nanotechnology gained significant importance to synthesize nanoparticles due to their cost effectiveness and biosafety. In the current study, silver nanoparticles were synthesized by using extract of Spirogyra hyalina as a capping and reducing agent. The synthesized nanoparticles were characterized by UV-Visible spectroscopy, Fourier transform infrared spectroscopy, Scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffractive analysis. Silver nanoparticles give a characteristic Surface Plasmon Resonance peak of 451 nm at 2.21 a.u (arbitrary unit). SEM micrograph revealed the spherical morphology and average grain size of 52.7 nm. Furthermore, antibacterial, antifungal, insecticidal, antioxidant and membrane damage activities were determined. The maximum antibacterial and antifungal activity was observed for Pseudomonas aeruginosa (18 ± 1.2 mm) and Fusarium solani (14.3 ± 0.6 mm), respectively. In membrane damage assay, Pseudomonas aeruginosa absorbed A260 wavelength and gave maximum peak values of 0.286, 0.434 and 0.629 at 25, 35 and 45 µg/mL of silver nanoparticles. The membrane damage assay confirmed that nanoparticles are involved in bacterial cell membrane damage. At 500 ppm silver nanoparticles showed 30% mortality against Tribolium castaneum (a common grain pest). The silver nanoparticles also showed potent antioxidant activity and successfully scavenged the DPPH free radicals upto 53.43 ± 0.17, 43.26 ± 0.97, 31.39 ± 0.33, 24.62 ± 0.85, and 14.13 ± 0.12% at a concentration of 400, 200, 100, 50, and 25 µg/mL of nanoparticles, respectively. It is concluded that silver nanoparticles can easily be synthesized by using green algae Spirogyra hyalina as a capping and reducing agent. Silver nanoparticles showed potent biomedical activities and thus can be used for therapeutic applications invitro and invivo.

18.
Curr Drug Targets ; 23(1): 99-113, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34365920

RESUMEN

The Angiotensin II type 2 Receptor (AT2R) is one of the critical components of the renin- angiotensin system (RAS), which performs diverse functions like inhibiting cell differentiation, cell proliferation, vasodilatation, reduces oxidative stress and inflammation. AT2R is relatively less studied in comparison to other components of RAS despite its uniqueness (sex-linked) and diverse functions. The AT2R is differentially expressed in different tissues, and its gene polymorphisms are associated with several diseases. The molecular mechanism behind the association of AT2R and its gene polymorphisms with the diseases remains to be fully understood, which hinders the development of AT2R as a drug target. Single nucleotide polymorphisms (SNPs) in AT2R are found at different locations (exons, introns, promoter, and UTR regions) and were studied for association with different diseases. There may be different mechanisms behind these associations as some AT2R SNP variants were associated with differential expression, the SNPs (A1675G/ A1332G) affect the alternate splicing of AT2R mRNA, A1332G genotype results in shortening of the AT2R mRNA and subsequently defective protein. Few SNPs were found to be associated with the diseases in either females (C4599A) or males (T1334C). Several other SNPs were expected to be associated with other similar/related diseases, but studies have not been done yet. The present review emphasizes on the significance of AT2R and its polymorphisms associated with the diseases to explore the precise role of AT2R in different diseases and the possibility to develop AT2R as a potential drug target.


Asunto(s)
Hipertensión , Receptor de Angiotensina Tipo 2 , Femenino , Humanos , Hipertensión/genética , Masculino , Polimorfismo de Nucleótido Simple , ARN Mensajero/metabolismo , Receptor de Angiotensina Tipo 2/genética , Sistema Renina-Angiotensina/genética
19.
Front Pharmacol ; 12: 600163, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33935698

RESUMEN

Acute kidney injury (AKI) due to endotoxemic insult is predicted by the infiltration of neutrophils, monocytes and macrophages, and the release of pro-and anti-inflammatory cytokines to the site of injury. Earlier, we have demonstrated the role of angiotensin-II type 2 receptor (AT2R) stimulation in reno-protection in lipopolysaccharide (LPS)-induced inflammation and AKI in C57BL6/NHsd mice. Moreover, AT2R activation has been shown to increase the anti-inflammatory cytokine interleukin-10 (IL-10), its role in AT2R-mediated anti-inflammation and reno-protection is unknown. To address this question, in the present study mice were treated with the AT2R agonist C21 (0.3 mg/kg, intraperitoneally), LPS (5 mg/kg, intraperitoneally), or LPS with C21 pre-treatment with or without neutralizing IL-10 antibody. Treatment with C21 alone caused an increase in the plasma and kidney IL-10 levels, which peaks at 2-h, and returned to baseline at 6-h. The C21-induced IL-10 increase was blocked by the AT2R antagonist PD123319 suggesting AT2R's involvement. LPS treatment caused a profound increase in tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the LPS-induced increase in these cytokines was attenuated by the C21 pre-treatment (1-h prior LPS) both in the plasma and kidney. Neutralizing IL-10 antibody treatment abrogated the C21-lowering of TNF-α and IL-6 in the kidney but not in the plasma. Similar results as related to the cytokines profiles in all the groups were also observed in the heart and spleen. The alteration in early cytokine profile prompted us to measure the markers of renal function (blood urea nitogen and urinary creatinine) in order to analyze the effect of IL-10 neutralization. However, it was too early to observe changes in renal function. Therefore, the renal function and injury markers were again measured at 24 h. Treatment with neutralizing IL-10 antibody attenuated the C21-mediated improvement in indices of the kidney function, but not the biomarkers of renal injury (kidney injury molecule-1 and neutrophil-gelatinase associated lipocalin). Collectively, our data suggest that the involvement of IL-10 in AT2R-mediated anti-inflammation and reno-protection against LPS is complex, mediating the renal cytokine profile and kidney filtration function, but not the plasma cytokine profile and renal injury markers.

20.
J Pak Med Assoc ; 71(2(B)): 708-712, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33941964

RESUMEN

OBJECTIVE: To analyse frequencies and results of anti-nuclear antibodies, anti-double stranded deoxyribonucleic acid and anti-extractable nuclear antigens tests ordered in a tertiary-care hospital. METHODS: The retrospective study was conducted at a tertiary care hospital in Karachi, and comprised all tests ordered for anti-nuclear antibodies, anti-double stranded deoxyribonucleic acid and anti-extractable nuclear antigens from March 2017 to January 2018. Data was retrieved from the institutional electronic database. The frequencies and results of the tests were determined. Anti-nuclear antibodies test was determined by indirect immunofluorescence, while the other two tests were determined by enzyme-linked immunosorbent assay. Patterns emerging from anti-nuclear antibodies tests were also analysed. RESULTS: Of the 1053 cases studied, 1000(95%) were tested for for anti-nuclear antibodies. The test was positive in 260(26%) patients, and was repeated in 8(3%) of the positive and 9(1.2%) of the negative patients. Anti-double stranded deoxyribonucleic acid test was ordered in 300(40.5%) and anti-extractable nuclear antigens test in 125(17%) patients who had tested negative for anti-nuclear antibodies. Among those who tested positive for anti-nuclear antibodies, the commonly observed patterns were homogenous 109(41.9%) and speckled 103(39.6%). Rod and ring pattern was seen in 10(3.8%) patients, and none of them were on anti-viral treatment. CONCLUSIONS: There was injudicious and unjustified ordering of auto-antibodies testing, indicating the need for greater physician education and cost-effective protocols.


Asunto(s)
Anticuerpos Antinucleares , Antígenos Nucleares , Humanos , Pakistán , Estudios Retrospectivos , Centros de Atención Terciaria
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