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1.
J Org Chem ; 89(1): 701-709, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38084730

RESUMO

NHC-Pd(II) pincer catalyzed oxidative amination and hydroamination of olefins is developed under solvent-free aerobic conditions. Reaction offered a temperature-controlled synthesis of (Z)-enamine and ß-amino esters to provide easy access and remarkable functional group tolerance for a variety of enamines. The developed approach renders an opportunity of scalability and flexibility, and besides this, the produced enamines can be transformed into many N-containing heterocycles, underscoring its potential usage in synthetic and pharmaceutical chemistry. Moreover, it is the first report for coupling of aniline with styrene.

2.
Int J Mol Sci ; 25(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38338960

RESUMO

The lipid endocannabinoid system has recently emerged as a novel therapeutic target for several inflammatory and tissue-damaging diseases, including those affecting the cardiovascular system. The primary targets of cannabinoids are cannabinoid type 1 (CB1) and 2 (CB2) receptors. The CB2 receptor is expressed in the cardiomyocytes. While the pathological changes in the myocardium upregulate the CB2 receptor, genetic deletion of the receptor aggravates the changes. The CB2 receptor plays a crucial role in attenuating the advancement of myocardial infarction (MI)-associated pathological changes in the myocardium. Activation of CB2 receptors exerts cardioprotection in MI via numerous molecular pathways. For instance, delta-9-tetrahydrocannabinol attenuated the progression of MI via modulation of the CB2 receptor-dependent anti-inflammatory mechanisms, including suppression of pro-inflammatory cytokines like IL-6, TNF-α, and IL-1ß. Through similar mechanisms, natural and synthetic CB2 receptor ligands repair myocardial tissue damage. This review aims to offer an in-depth discussion on the ameliorative potential of CB2 receptors in myocardial injuries induced by a variety of pathogenic mechanisms. Further, the modulation of autophagy, TGF-ß/Smad3 signaling, MPTP opening, and ROS production are discussed. The molecular correlation of CB2 receptors with cardiac injury markers, such as troponin I, LDH1, and CK-MB, is explored. Special attention has been paid to novel insights into the potential therapeutic implications of CB2 receptor activation in MI.


Assuntos
Canabinoides , Infarto do Miocárdio , Receptor CB1 de Canabinoide , Humanos , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Canabinoides/metabolismo , Endocanabinoides/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/genética , Receptor CB2 de Canabinoide/metabolismo , Receptores de Canabinoides/metabolismo , Dronabinol/farmacologia
3.
J Am Chem Soc ; 145(32): 17819-17830, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37543962

RESUMO

Programmable chemical circuits inspired by signaling networks in living cells are a promising approach for the development of adaptive and autonomous self-assembling molecular systems and material functions. Progress has been made at the molecular level, but connecting molecular control circuits to self-assembling larger elements such as colloids that enable real-space studies and access to functional materials is sparse and can suffer from kinetic traps, flocculation, or difficult system integration protocols. Herein, we report a toehold-mediated DNA strand displacement reaction network capable of autonomously directing two different microgels into transient and self-regulating co-assemblies. The microgels are functionalized with DNA and become elemental components of the network. The flexibility of the circuit design allows the installation of delay phases or accelerators by chaining additional circuit modules upstream or downstream of the core circuit. The design provides an adaptable and robust route to regulate other building blocks for advanced biomimetic functions.


Assuntos
Microgéis , DNA/química , Transdução de Sinais , Cinética , Coloides
4.
J Viral Hepat ; 30(12): 959-969, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37697495

RESUMO

Hepatitis E is a disease associated with acute inflammation of the liver. It is related to several dysregulated metabolic pathways and alterations in the concentration of several metabolites. However, longitudinal analysis of the alterations in metabolites and lipids is generally lacking. This study investigated the changes in levels of metabolites and lipids over time in sera from men with acute hepatitis E compared to healthy controls similar in age and gender. Untargeted measurement of levels of various metabolites and lipids was done using mass spectrometry on 65 sera sequentially sampled from 14 patients with acute hepatitis E and 25 serum samples from five controls. Temporal changes in intensities of metabolites and lipids were determined over different times at 3-day periods for the hepatitis E virus (HEV) group. In carbohydrate metabolism, glucose levels, fructose 1-6-bisphosphate and ribulose-5-phosphate were increased in the HEV-infected persons compared to the healthy controls. HEV infection is significantly associated with decreased levels of inosine, guanosine, adenosine and urate in purine metabolism and thymine, uracil and ß-aminoisobutyrate in pyrimidine metabolism. Glutamate, alanine and valine levels were significantly lower in the HEV group than in healthy individuals. Homogentisate of tyrosine metabolism and cystathionine of serine metabolism were increased, whereas kynurenate of tryptophan metabolism decreased in the HEV group. Metabolites of the bile acid biosynthesis, urea cycle (arginine and citrulline) and ammonia recycling (urocanate) were significantly altered. Co-enzymes, pantothenate and pyridoxal, and co-factors, lipoamide and FAD, were elevated in the HEV group. The acylcarnitines, sphingomyelins, phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysoPC and lysoPE tended to be lower in the HEV group. In conclusion, acute hepatitis E is associated with altered metabolite and lipid profiles, significantly increased catabolism of carbohydrates, purines/pyrimidines and amino acids, and decreased levels of several glycerophospholipids.


Assuntos
Vírus da Hepatite E , Hepatite E , Masculino , Humanos , Estudos Longitudinais , Lipídeos
5.
Langmuir ; 39(36): 12865-12877, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37639338

RESUMO

The MoS2-based reduced graphene oxide aerogel (MoS2-rGOA)-assisted organic transformation reactions are presented. MoS2-rGOA is used as a heterogeneous catalyst for the reduction of benzene derivatives such as benzaldehyde, nitrobenzene, and benzonitrile to benzyl alcohol, aniline, and benzamide and their derivatives, respectively, in green solvents (water/methanol) and green reducing agents (hydrazine hydrate having N2 and H2 as byproducts). The mechanistic features of the reduction pathway, substrate scope, and the best suitable conditions by varying the temperature, solvent, reducing agent, catalyst loading, time, etc. are optimized. All of the synthesized products are obtained in quantitative yield with purity and well characterized based on nuclear magnetic resonance analysis. Further, it is also observed that our catalyst is efficiently recyclable and works well checked up to 5 cycles.

6.
Am J Obstet Gynecol ; 2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38151222

RESUMO

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

7.
Int J Mol Sci ; 24(2)2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36674739

RESUMO

Sirolimus (SRL) is widely used as an immunosuppressant to prevent graft rejection, despite the risk of impairing glucose metabolism. Metformin (MET) can reduce the detrimental effects of SRL in many patients, including diabetes and renal transplant recipients. Limited in vivo studies have reported on SRL and MET therapy, particularly in relation to cellular bioenergetics, glucose metabolism, and insulin resistance. Herein, we investigated the efficacy of SRL and MET co-treatment in BALB/c mice over 4 weeks. Balb/c mice (4-6 weeks old) were divided into four groups and injected intraperitoneally (i.p.) with water (control, CTRL), MET (200 µg/g), SRL (5 µg/g), or MET (200 µg/g) +SRL (5 µg/g) over a period of one month. We evaluated the body weight, food consumption rate, random blood glucose (BG), insulin levels, serum biochemistry parameters (ALT, Albumin, BUN, Creatinine), and histomorphology in all groups using standardized techniques and assays. All drug-treated groups showed a statistically significant decrease in weight gain compared to the CTRL group, despite normal food intake. Treatment with SRL caused elevated BG and insulin levels, which were restored with SRL + MET combination. Serum biochemical parameters were within the normal range in all the studied groups. SRL+ MET co-treatment decreased liver cellular respiration and increased cellular ATP levels in the liver. In the pancreas, co-treatment resulted in increased cellular respiration and decreased cellular ATP levels. Liver and pancreatic histology were unchanged in all groups. This study showed that co-treatment of SRL with MET alleviates hyperglycemia induced by SRL without any deleterious effects. These results provide initial insights into the potential use of SRL + MET therapy in various settings.


Assuntos
Hiperglicemia , Insulinas , Metformina , Animais , Camundongos , Sirolimo/farmacologia , Metformina/farmacologia , Camundongos Endogâmicos BALB C , Imunossupressores , Hiperglicemia/tratamento farmacológico , Hiperglicemia/induzido quimicamente , Respiração Celular , Glucose , Trifosfato de Adenosina , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle
8.
Int J Mol Sci ; 24(3)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36769305

RESUMO

Psoriasis is linked with unusual differentiation and hyperproliferation of epidermal keratinocytes that significantly impair the quality of life (QoL) of patients. The present treatment options only provide symptomatic relief and are surrounded by various adverse effects. Recently, nanostructured lipid carriers (NLCs) have emerged as next-generation nanocarriers with better physicochemical characteristics. The current manuscript provides background information on psoriasis, its pathophysiology, existing treatment options, and its limitations. It highlights the advantages, rationale, and mechanism of the permeation of NLCs for the treatment of psoriasis. It further gives a detailed account of various NLC nanoformulations for the treatment of psoriasis. In addition, tabular information is provided on the most relevant patents on NLCs for treating psoriasis. Lastly, light is shed on regulatory considerations related to NLC-like nanoformulations. In the treatment of psoriasis, NLCs display a sustained release drug profile, an ability to incorporate both hydrophobic and hydrophilic drugs, an enhancement in skin hydration, penetrability, retention, and bioavailability of the drug, along with reduced staining potential as compared to conventional ointments, and decreased side effects of drug molecules. This affirms the bright future of NLC nanoformulations in the treatment of psoriasis. However, academic industry collaboration and more sound regulatory controls are required to commercialize the NLC nanoformulations for psoriasis treatment.


Assuntos
Nanoestruturas , Psoríase , Humanos , Qualidade de Vida , Portadores de Fármacos/química , Pele/metabolismo , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Nanoestruturas/química , Lipídeos/química , Tamanho da Partícula , Liberação Controlada de Fármacos
9.
Eur J Contracept Reprod Health Care ; 28(3): 153-162, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36995695

RESUMO

PURPOSE: The objective of the study was to see the difference in expulsion rates of two types of Copper containing intrauterine contraceptive devices (IUCDs): Cu 375 & CuT 380 A, within or at 6 weeks after insertion. METHODS: It was a randomised control trial. A total of 396 pregnant women were recruited. Ultrasonography was done to look for the position of the IUCD at the time of discharge and at six weeks follow-up and the expulsion rate was calculated. RESULTS: Amongst 396 participants, 22 PPIUCDs were expelled completely at 6 weeks (modified intention to treat analysis [ITA]), 10 (5.3%) and 12 (6.7%) in the Cu 375 and CuT 380 A groups respectively. The expulsion rate was 6.02%. However, this difference was not statistically significant. When ultrasonologically assessed partial expulsions were also considered, the total expulsion rate in both groups (14.3% and 14.1% respectively) was also not significantly different. The expulsion rate was higher in the vaginal delivery group (10.7%) than in the caesarean section (3.6%) group (p = 0.007) and early postpartum insertion 12.3% than in the immediate post-placental insertion group, 3.7% (p = 0.002). CONCLUSIONS: The study concluded that the altered shape of Cu 375 has effectively no role in decreasing the expulsion rate. Placement of IUCD at or near the uterine fundus immediately after delivering the placenta (post-placental) decreases the expulsion rate, thereby increasing the contraceptive efficacy.SHORT CONDENSATIONThe altered shape of Cu 375 has effectively no role in decreasing the expulsion rate. Placement of IUCD at or near the uterine fundus immediately after delivering the placenta (post-placental) decreases the expulsion rate, thereby increasing the contraceptive efficacy.


Assuntos
Dispositivos Intrauterinos de Cobre , Dispositivos Intrauterinos , Gravidez , Feminino , Humanos , Cobre , Cesárea , Estudos Prospectivos , Placenta , Período Pós-Parto , Anticoncepcionais , Expulsão de Dispositivo Intrauterino
10.
J Obstet Gynaecol Res ; 48(7): 1955-1960, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35580870

RESUMO

OBJECTIVE: The goal of this study was to analyze how the COVID-19 pandemic affected the Obstetrics and Gynecology (OBG) residency program in India. STUDY DESIGN: This was a cross-sectional questionnaire-based online survey aimed to assess the impact of the pandemic on the residency training program in Obstetrics and Gynecology. The questionnaire consisted of five sections: demographic details, information regarding COVID-19 status, clinical work load, teaching and research, and psychological impact. RESULTS: The questionnaire was completed by 280 OBG trainees from different medical colleges from India. Training activity in general was reduced considerably during the pandemic, according to 79.6% (n = 223) respondents. According to 13.21% (n = 37) and 5% (n = 14) respondents, reduction in training activity were due to cancelation of elective operations and reduced patient foot fall respectively. In 74.3% (n = 208) of cases, trainees reported worry about meeting the goals of their specialty training. Logistic regression showed that the extent of training reduction was not significantly associated with residents' age (p = 0.806), gender (p = 0.982), marital status (p = 0.363), and status of their duty in COVID-19 dedicated hospitals (p = 0.110). However, year of residency was a significant predictor of the perception about degree of training reduction. CONCLUSION: The pandemic imposed a significant impact on OBG residency training in India. During the pandemic, exposure to learning opportunities, surgeries, and teaching were reduced, which may result in a decline in the quality of care offered to women in the future if training deficit is not overcome. At the same time, pandemic also gave birth to newer insights of learning and interaction by online mode.


Assuntos
COVID-19 , Ginecologia , Internato e Residência , Obstetrícia , COVID-19/epidemiologia , Estudos Transversais , Feminino , Ginecologia/educação , Humanos , Obstetrícia/educação , Pandemias , Gravidez , Inquéritos e Questionários
11.
Molecules ; 27(11)2022 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-35684428

RESUMO

A lethal condition at the arterial-alveolar juncture caused the exhaustive remodeling of pulmonary arterioles and persistent vasoconstriction, followed by a cumulative augmentation of resistance at the pulmonary vascular and, consequently, right-heart collapse. The selective dilation of the pulmonary endothelium and remodeled vasculature can be achieved by using targeted drug delivery in PAH. Although 12 therapeutics were approved by the FDA for PAH, because of traditional non-specific targeting, they suffered from inconsistent drug release. Despite available inhalation delivery platforms, drug particle deposition into the microenvironment of the pulmonary vasculature and the consequent efficacy of molecules are influenced by pathophysiological conditions, the characteristics of aerosolized mist, and formulations. Uncertainty exists in peripheral hemodynamics outside the pulmonary vasculature and extra-pulmonary side effects, which may be further exacerbated by underlying disease states. The speedy improvement of arterial pressure is possible via the inhalation route because it has direct access to pulmonary arterioles. Additionally, closed particle deposition and accumulation in diseased tissues benefit the restoration of remolded arterioles by reducing fallacious drug deposition in other organs. This review is designed to decipher the pathological changes that should be taken into account when targeting the underlying pulmonary endothelial vasculature, especially with regard to inhaled particle deposition in the alveolar vasculature and characteristic formulations.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Administração por Inalação , Pressão Arterial , Sistemas de Liberação de Medicamentos , Humanos , Hipertensão Pulmonar/tratamento farmacológico
12.
Angew Chem Int Ed Engl ; 61(19): e202201573, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35235231

RESUMO

Biological self-assemblies self- and cross-regulate each other via chemical reaction networks (CRNs) and feedback. Although artificial transient self-assemblies have been realized via activation/deactivation CRNs, the transient structures themselves do mostly not engage in the CRN. We introduce a rational design approach for chemo-structural feedback, and present a transient colloidal co-assembly system, where the formed co-assemblies accelerate their destruction autonomously. We achieve this by immobilizing enzymes of a deactivating acid-producing enzymatic cascade on pH-switchable microgels that can form co-assemblies at high pH. Since the enzyme partners are immobilized on individual microgels, the co-assembled state brings them close enough for enhanced acid generation. The amplified deactivator production (acid) leads to an almost two-fold reduction in the lifetime of the transiently formed pH-state. Our study thus introduces versatile mechanisms for chemo-structural feedback.


Assuntos
Microgéis , Retroalimentação
13.
Ann Hum Genet ; 85(2): 48-57, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32970831

RESUMO

Type 1 diabetes (T1D) is a chronic autoimmune disease with a complex interrelation of genetic and environmental factors. Genetic studies have reported HLA and non-HLA loci as significant contributors to T1D. However, the genetic basis of T1D among Emiratis is unexplored. This study aims to determine the contribution of four genes PTPN22, CTLA-4, IL2-RA, and INS to T1D risk among Emiratis. The association between variants in PTPN22 (rs2476601, rs1310182), CTLA-4 (rs11571316, rs231775, rs3087243, rs1427676, and rs231727), IL2-RA (rs7090530), and INS (rs7111341) with T1D was tested in 310 Emiratis (139 T1D patients and 171 controls). A significant association was found at rs1310182, and rs2476601 both in PTPN22, rs3087243, and rs231775 both in CTLA-4, and rs12251307 in IL2-RA. Moreover, a haplotype constituted from GG and AG genotypes at rs231727 and rs231775, respectively, in CTLA-4 was significantly associated with an increased T1D risk. The cumulative effects of risk alleles for all significantly associated SNPs showed 11.8 higher relative risk for T1D for those who carry 5-6 compared to 0-1 risk alleles. This study illustrated that PTPN22, CTLA-4, and IL2-RA gene variants could confer risk alleles for T1D among the Emirati population.


Assuntos
Antígeno CTLA-4/genética , Diabetes Mellitus Tipo 1/genética , Insulina/genética , Subunidade alfa de Receptor de Interleucina-2/genética , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Adolescente , Adulto , Alelos , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/patologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Haplótipos/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Emirados Árabes Unidos/epidemiologia , Adulto Jovem
14.
Int J Med Sci ; 18(15): 3526-3532, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522179

RESUMO

Background: Acute myocardial infarction is a relatively rare phenomenon in the young population. The incidence has nevertheless increased from years past, likely due to the presence of multiple risk factors from an increasingly younger age. Regardless of whether they have atherosclerotic coronary artery disease or normal coronary angiogram, young patients with risk factors for coronary artery disease (CAD), chest pain, and positive troponin, are initially treated in a similar fashion. Our goal was to shed light on whether risk factors between these two groups differ to help guide physicians in clinically determining whether or not an atherosclerotic cardiovascular event has occurred, as well as to potentially identify young patients at risk of acute coronary syndrome (ACS) despite normal coronary arteries. Methods: A retrospective cross sectional study was undertaken over an 8 year period at Tawam Hospital. 576 patients aged 50 or under who underwent coronary angiography were selected for the study. Medical records were analyzed for the patient's demographics and CAD risk factor profile, including the following variables: family history of CAD, smoking status, Body Mass Index category, lipid profile, and diagnosis of hyperlipidemia, diabetes, or hypertension. Details of the coronary angiogram were also reviewed. Results: Statistically significant outcomes included a higher prevalence of diabetes, hyperlipidemia, and smoking history in patients with CAD compared to the patients with normal coronary angiogram. Diabetes was one of the strongest risk factors in CAD patients, with an odds ratio of 1.98 (p= 0.011), followed by hyperlipidemia at 1.85 (p= 0.021). Smoking history had an odds ratio of 2.93 (p <0.001). Conclusion: Risk factors were present in both groups, but significantly more in the CAD group. No particular risk factor stood out for the development of ACS in those with normal coronary arteries, other than mean BMI being slightly higher in this group. Based on our analysis, no single variable can accurately predict the risk for ACS in normal coronaries. To our knowledge, few studies have been done in the young population with angiographically normal coronary arteries to determine possible risk factors for development of ACS. Further research needs to be done to determine whether the risk factors that were common amongst both groups are coincidental, or a cause of ACS in those with normal coronary arteries.


Assuntos
Síndrome Coronariana Aguda/etiologia , Aterosclerose/etiologia , Angiografia Coronária , Doença da Artéria Coronariana/etiologia , Fatores de Risco de Doenças Cardíacas , Síndrome Coronariana Aguda/epidemiologia , Adulto , Aterosclerose/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Diabetes Mellitus/diagnóstico por imagem , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/diagnóstico por imagem , Hiperlipidemias/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fumar/efeitos adversos , Fumar/epidemiologia , Taiwan/epidemiologia
15.
Drug Dev Res ; 82(1): 7-11, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33190277

RESUMO

The COVID-19 pandemic caused by SARS-CoV-2 is a deadly disease afflicting millions. The pandemic continues affecting population due to nonavailability of drugs and vaccines. The pathogenesis and complications of infection mainly involve hyperimmune-inflammatory responses. Thus, therapeutic strategies rely on repurposing of drugs aimed at reducing infectivity and inflammation and modulate immunity favourably. Among, numerous therapeutic targets, the endocannabinoid system, particularly activation of cannabinoid type-2 receptors (CB2R) emerged as an important one to suppress the hyperimmune-inflammatory responses. Recently, potent antiinflammatory, antiviral and immunomodulatory properties of CB2R selective ligands of endogenous, plant, and synthetic origin were showed mediating CB2R selective functional agonism. CB2R activation appears to regulate numerous signaling pathways to control immune-inflammatory mediators including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. Many CB2R ligands also exhibit off-target effects mediating activation of PPARs, opioids, and TRPV, suggestive of adjuvant use with existing drugs that may maximize efficacy synergistically and minimize therapeutic doses to limit adverse/ side effects. We hypothesize that CB2R agonists, due to immunomodulatory, antiinflammatory, and antiviral properties may show activity against COVID-19. Based on the organoprotective potential, relative safety, lack of psychotropic effects, and druggable properties, CB2R selective ligands might make available promising candidates for further investigation.


Assuntos
Tratamento Farmacológico da COVID-19 , Agonistas de Receptores de Canabinoides/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Imunidade Celular/efeitos dos fármacos , Receptor CB2 de Canabinoide/agonistas , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/metabolismo , COVID-19/imunologia , COVID-19/metabolismo , Agonistas de Receptores de Canabinoides/metabolismo , Humanos , Imunidade Celular/fisiologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/metabolismo , Receptor CB2 de Canabinoide/imunologia , Receptor CB2 de Canabinoide/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/metabolismo
16.
Molecules ; 26(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803259

RESUMO

Ezetimibe (EZE) possesses low aqueous solubility and poor bioavailability and in addition, its extensive hepatic metabolism supports the notion of developing a novel carrier system for EZE. Ezetimibe was encapsulated into nanostructured lipid carriers (EZE-NLCs) via a high pressure homogenization technique (HPH). A three factor, two level (23) full factorial design was employed to study the effect of amount of poloxamer 188 (X1), pressure of HPH (X2) and number of HPH cycle (X3) on dependent variables. Particle size, polydispersity index (PDI), % entrapment efficiency (%EE), zeta potential, drug content and in-vitro drug release were evaluated. The optimized formulation displays pragmatic inferences associated with particle size of 134.5 nm; polydispersity index (PDI) of 0.244 ± 0.03; zeta potential of -28.1 ± 0.3 mV; % EE of 91.32 ± 1.8% and % CDR at 24-h of 97.11%. No interaction was observed after X-ray diffraction (XRD) and differential scanning calorimetry (DSC) studies. EZE-NLCs (6 mg/kg/day p.o.) were evaluated in the high fat diet fed rats induced hyperlipidemia in comparison with EZE (10 mg/kg/day p.o.). Triglyceride, HDL-c, LDL-c and cholesterol were significantly normalized and histopathological evaluation showed normal structure and architecture of the hepatocytes. The results demonstrated the superiority of EZE-NLCs in regard to bioavailability enhancement, dose reduction and dose-dependent side effects.


Assuntos
Ezetimiba/farmacologia , Hiperlipidemias/tratamento farmacológico , Nanotecnologia/métodos , Animais , Disponibilidade Biológica , Dieta Hiperlipídica/efeitos adversos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Ezetimiba/administração & dosagem , Hiperlipidemias/metabolismo , Lipídeos/química , Lipídeos/farmacologia , Masculino , Nanopartículas/química , Nanoestruturas/química , Tamanho da Partícula , Ratos , Ratos Wistar , Solubilidade , Triglicerídeos , Difração de Raios X
17.
Angew Chem Int Ed Engl ; 60(41): 22537-22546, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34347941

RESUMO

Compartmentalized reaction networks regulating signal processing, communication and pattern formation are central to living systems. Towards achieving life-like materials, we compartmentalized urea-urease and more complex urea-urease/ester-esterase pH-feedback reaction networks into hydrogel spheres and investigate how fuel-driven pH fronts can be sent out from these spheres and regulated by internal reaction networks. Membrane characteristics are installed by covering urease spheres with responsive hydrogel shells. We then encapsulate the two networks (urea-urease and ester-esterase) separately into different hydrogel spheres to devise communication, pattern formation and attraction. Moreover, these pH fronts and patterns can be used for self-growing hydrogels, and for developing complex geometries from non-injectable hydrogels without 3D printing tools. This study opens possibilities for compartmentalized feedback reactions and their use in next generation materials fabrication.

18.
Am J Physiol Renal Physiol ; 319(5): F833-F838, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33017190

RESUMO

Angiotensin II drives the pathogenesis of diabetic kidney disease, and its systemic administration induces glomerular hyperpermeability in normal rats. However, the response of diabetic glomerular permeability to angiotensin II is largely unknown. In the present study, we investigated the impact of extended systemic administration of angiotensin II on the glomerular permeability of streptozotocin (STZ)-induced late diabetes in rats. We examined the changes in the glomerular permeability after subcutaneous infusion of angiotensin II at 200 ng·kg-1·min-1 for 7 days in male Wistar diabetic rats with 3 mo of STZ-induced diabetes (i.e., blood glucose of ∼20 mmol/L). We also compared these changes with the effects on nondiabetic rats. The sieving coefficients (θ) for inert polydisperse Ficoll molecules, which had a radius of 10-90 Å (Ficoll70-90 Å), were measured in vivo. The θ for large Ficoll molecules was selectively enhanced after infusion of extended angiotensin II in both diabetic (θ for Ficoll70-90 Å = 0.00244 vs. 0.00079, P < 0.001) and nondiabetic animals (θ for Ficoll70-90 Å = 0.00029 vs. 0.00006, P < 0.001). These changes were compatible with the more than twofold increase in the macromolecular glomerular transport through the large-pore pathways after infusion of angiotensin II in both diabetic and nondiabetic animals. Angiotensin II infusion enhanced the large shunt-like glomerular transport pathway of STZ-induced late diabetes. Such defects can account for the large-molecular-weight IgM-uria that is observed in severe diabetic kidney disease.


Assuntos
Angiotensina II/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomérulos Renais/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Ficoll/metabolismo , Glomérulos Renais/metabolismo , Masculino , Ratos Wistar
19.
Org Biomol Chem ; 18(15): 2921-2928, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32239077

RESUMO

A tandem cleavage of carbon-carbon and carbon-nitrogen bonds in imidazo[1,2-a]pyridines and imidazo[1,2-a]quinolines is reported in the presence of eosin Y and visible light. The ring opening occurs under ambient conditions through singlet oxygen insertion, bond cleavage and CO2 elimination, and produces N-(pyridin-2-yl) amides and N-(quinolin-2-yl) amides in high yields. The reaction shows good versatility, and does not require strong external oxidants and additives.

20.
Org Biomol Chem ; 18(18): 3599-3606, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32347877

RESUMO

Three new pyrazolated chalcogenoether ligated Rh(iii) half-sandwich complexes (1-3) were synthesised by the thermal reaction of chalcogenoether (S, Se and Te) substituted 1H-pyrazole ligands (L1-L3) and [(η5-C5Me5)RhCl]2 in methanol. The complexes were fully characterised by various spectroscopic techniques, and the molecular structures of complexes 1 and2 were also established through single crystal X-ray crystallographic analysis, which indicates a pseudo-octahedral half-sandwich piano-stool geometry around the rhodium metal. All three complexes were found to be thermally stable and insensitive towards air and moisture. One mol% of Rh(iii) complexes (1-3) along with 10 mol% of Cu(OAc)2 were explored for the Buchwald-Hartwig type C-N coupling reactions of amine and aryl chloride. Good to excellent yields (89-92%) of the coupling products were obtained with seleno- and thio-ether functionalised pyrazolated Rh(iii) complexes (1 and 2), while an average yield (39%) was obtained with the telluro-ether functionalised complex (3). In contrast to the previously reported C-N coupling reactions the present reaction works under solvent- and base-free conditions, and the coupling reaction is accomplished in just 6 h with a high yield of the coupling product. The present methodology was also found to be efficient for a wide variety of functionalised aryl halides, and aliphatic or aromatic amines (1° and 2°). Moreover, the reaction also enables the C-N coupling of electron-withdrawing substrates and base-sensitive functionalities.

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