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1.
Int J Mol Sci ; 24(11)2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37298092

RESUMO

People living with HIV (PLWH) have an elevated risk of chronic obstructive pulmonary disease (COPD) and are at a higher risk of asthma and worse outcomes. Even though the combination of antiretroviral therapy (cART) has significantly improved the life expectancy of HIV-infected patients, it still shows a higher incidence of COPD in patients as young as 40 years old. Circadian rhythms are endogenous 24 h oscillations that regulate physiological processes, including immune responses. Additionally, they play a significant role in health and diseases by regulating viral replication and its corresponding immune responses. Circadian genes play an essential role in lung pathology, especially in PLWH. The dysregulation of core clock and clock output genes plays an important role in chronic inflammation and aberrant peripheral circadian rhythmicity, particularly in PLWH. In this review, we explained the mechanism underlying circadian clock dysregulation in HIV and its effects on the development and progression of COPD. Furthermore, we discussed potential therapeutic approaches to reset the peripheral molecular clocks and mitigate airway inflammation.


Assuntos
Relógios Circadianos , Infecções por HIV , Doença Pulmonar Obstrutiva Crônica , Humanos , Adulto , Relógios Circadianos/genética , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/genética , Pulmão/patologia , Ritmo Circadiano/genética , Inflamação/metabolismo , Infecções por HIV/complicações , Infecções por HIV/genética , Infecções por HIV/metabolismo
2.
Biochem Biophys Res Commun ; 523(2): 342-347, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-31866011

RESUMO

Ribonuclease P (RNase P) is an RNA processing enzyme essential for production of functional tRNAs. Bacterial RNase P is a ribozyme, i.e., an RNA-based enzyme, which functions in all bacteria including those growing at high temperatures (≥55 °C). We examined three bacterial RNase P ribozymes, one from a mesophilic bacterium and two from thermophilic bacteria, to understand the factor(s) providing efficient catalytic ability under conditions of high temperature. Thermophilic RNase P ribozymes show structural adaptations to allow correct folding at high temperature. The presence of a molecular crowder significantly enhanced the catalytic efficiency of thermophilic RNase P ribozyme reactions at 55 °C, while it modestly reduced the upper limit of the reaction temperature.


Assuntos
Proteínas de Bactérias/metabolismo , Ribonuclease P/metabolismo , Proteínas de Bactérias/química , Biocatálise , Escherichia coli/enzimologia , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Temperatura Alta , Cinética , Conformação de Ácido Nucleico , Dobramento de Proteína , Estrutura Secundária de Proteína , Precursores de RNA/química , Precursores de RNA/metabolismo , RNA Bacteriano/química , RNA Bacteriano/metabolismo , Ribonuclease P/química , Thermotoga maritima/enzimologia , Termotolerância , Thermus thermophilus/enzimologia
3.
Int J Mol Sci ; 21(16)2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32824102

RESUMO

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder related to age, characterized by the cerebral deposition of fibrils, which are made from the amyloid-ß (Aß), a peptide of 40-42 amino acids. The conversion of Aß into neurotoxic oligomeric, fibrillar, and protofibrillar assemblies is supposed to be the main pathological event in AD. After Aß accumulation, the clinical symptoms fall out predominantly due to the deficient brain clearance of the peptide. For several years, researchers have attempted to decline the Aß monomer, oligomer, and aggregate levels, as well as plaques, employing agents that facilitate the reduction of Aß and antagonize Aß aggregation, or raise Aß clearance from brain. Unluckily, broad clinical trials with mild to moderate AD participants have shown that these approaches were unsuccessful. Several clinical trials are running involving patients whose disease is at an early stage, but the preliminary outcomes are not clinically impressive. Many studies have been conducted against oligomers of Aß which are the utmost neurotoxic molecular species. Trials with monoclonal antibodies directed against Aß oligomers have exhibited exciting findings. Nevertheless, Aß oligomers maintain equivalent states in both monomeric and aggregation forms; so, previously administered drugs that precisely decrease Aß monomer or Aß plaques ought to have displayed valuable clinical benefits. In this article, Aß-based therapeutic strategies are discussed and several promising new ways to fight against AD are appraised.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/antagonistas & inibidores , Amiloide/metabolismo , Modelos Biológicos , Peptídeos beta-Amiloides/metabolismo , Animais , Biomarcadores/metabolismo , Humanos , Proteínas tau/metabolismo
4.
BMC Complement Altern Med ; 17(1): 423, 2017 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-28836990

RESUMO

BACKGROUND: Euphorbia hirta linn., is a species of Euphorbiaceae family. They are known as asthma plant, barokhervi. The plant E. hirta is famous for its medicinal importance among the tribal population. It is a common practice to use the whole to heal wounds. Several pharmacological properties including antiseptic, anti-inflammatory, antidibetic, antispasmodic, antibacterial, antiviral, antifungal, anticonvulsant, nootropic, antifertility and aphrodisiac properties have already been reported for this plant. The aim of present work was to evaluate the wound healing property in diabetic animals by oral and topical administration of ethanolic extract of E. hirta whole plant. METHODS: The ethanolic extract of E. hirta was subjected to determine the total phenolic content and total flavonoid content using galic acid and quercetin, respectively as standard. A single injection of alloxan monohydrate (120 mg/kg, i.p.) prepared in normal saline was administered to produce diabetes in rats, after overnight fasting. For analyzing the rate of contraction of wound, excision wounds sized 4.90cm2 and of 2 mm depth were used. Oral (100, 200 and 400 mg/kg/day; p.o.) and topical treatment with the extract (5% and 10% ointment 50 mg/kg/day) and standard (5% povidone iodine ointment 50 mg/kg/day) was started on the day of induction of wound and continued up to 16 days. The means of wound area measurement between groups at different time intervals were compared using ANOVA and Dunnet's test. The diabetic wound healing mechanism was studied by measuring the plasma level of glucose, malondialdehyde (MDA) and nitric oxide (NO) in both control and treated groups. For the confirmation of activity, histopathology of the wounds tissues from excision wound model was performed. RESULTS: Phytochemical investigations showed the presence of various phytoconstituents (carbohydrates, saponins, alkaloids, glycosides, steroids, flavonoids, tannins). In the ethanolic extract of E. hirta the total phenol content was 285 ± 3.22 mg/g whereas the total flavonoid content was 118.46 ± 1.85 mg/g. In the present study, E. hirta caused significant wound closer both orally (35.92%, 44.69% and 61.42% at the doses of 100, 200 and 400, respectively) and topically (32.86% and 36.32% at the doses of 5% and 10%) treated groups as compared to diabetic control. However, the orally treated groups showed more significant effect than the topically treated groups. Moreover, oral administration of E. hirta ethanolic extract significantly reduced the blood glucose levels in diabetic wound rats (p < 0.01) on day 8 and day 16 as compared to the diabetic wound control (p < 0.01). On the other hand, topical application of E. hirta did not influence the blood glucose levels in diabetic rats (p > 0.05). It also demonstrated a significant decrease in the plasma levels of lipid malondialdehyde and nitric oxide. The results of biochemical parameters were further supported by the histopathological changes of different organs (liver, pancrease, kidney, heart and skin from wound area) which were evidenced through a decrease in inflammatory cell infiltration. CONCLUSION: The present study demonstrates that E. hirta whole plant extract promotes healing of wounds more significantly as compared to diabetic control rats, where healing is otherwise delayed.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Euphorbia/química , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Aloxano , Animais , Glicemia/efeitos dos fármacos , Feminino , Flavonoides , Extratos Vegetais/uso terapêutico , Polifenóis , Ratos , Pele/efeitos dos fármacos , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/patologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-38953454

RESUMO

Our objectives were to ascertain the following: (1) the prevalence and socioeconomic distribution of hypertension (HTN), undiagnosed for HTN, and untreated cases of HTN-diagnosed individuals; (2) the relationship between SES and the prevalence of HTN, undiagnosed for HTN, and untreated for HTN; and (3) whether sex moderate this association. Data from the 2017-18 Bangladesh Demographic Health Survey were used. 11,776 participants who were 18 years of age or older responded to our analysis. The age-adjusted prevalence of HTN, undiagnosed for HTN, and untreated cases was 25.1%, 57.2%, and 12.3%. Compared to females, males were less likely to have HTN but more likely to have undiagnosed HTN. People in the rich SES groups had a higher odd of (adjusted odds ratio [aoR] 1.25; 95% confidence interval [CI] 1.08-3.45) of having HTN compared to those in the poor SES group. When compared to individuals in the poor SES group, those in the rich SES group had lower odds of undiagnosed (aoR 0.57; 95% CI 0.44-0.74) and untreated (aoR 0.56; 95% CI 0.31-0.98) for HTN. Sex moderated the association between SES and HTN prevalence, which showed that men from rich SES were more likely to suffer from HTN than men from poor SES. According to this study, the government and other pertinent stakeholders should concentrate more on developing suitable policy measures to reduce the risk of HTN, particularly for men in rich socioeconomic groups. They should also concentrate on screening and diagnosing HTN in socioeconomically disadvantaged populations, regardless of sex.

6.
Pharmaceutics ; 16(3)2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38543301

RESUMO

The continuous evolution of new viruses poses a danger to world health. Rampant outbreaks may advance to pandemic level, often straining financial and medical resources to breaking point. While vaccination remains the gold standard to prevent viral illnesses, these are mostly prophylactic and offer minimal assistance to those who have already developed viral illnesses. Moreover, the timeline to vaccine development and testing can be extensive, leading to a lapse in controlling the spread of viral infection during pandemics. Antiviral therapeutics can provide a temporary fix to tide over the time lag when vaccines are not available during the commencement of a disease outburst. At times, these medications can have negative side effects that outweigh the benefits, and they are not always effective against newly emerging virus strains. Several limitations with conventional antiviral therapies may be addressed by nanotechnology. By using nano delivery vehicles, for instance, the pharmacokinetic profile of antiviral medications can be significantly improved while decreasing systemic toxicity. The virucidal or virus-neutralizing qualities of other special nanomaterials can be exploited. This review focuses on the recent advancements in nanomedicine against RNA viruses, including nano-vaccines and nano-herbal therapeutics.

7.
Diagnostics (Basel) ; 13(11)2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37296800

RESUMO

Heart failure is a devastating disease that has high mortality rates and a negative impact on quality of life. Heart failure patients often experience emergency readmission after an initial episode, often due to inadequate management. A timely diagnosis and treatment of underlying issues can significantly reduce the risk of emergency readmissions. The purpose of this project was to predict emergency readmissions of discharged heart failure patients using classical machine learning (ML) models based on Electronic Health Record (EHR) data. The dataset used for this study consisted of 166 clinical biomarkers from 2008 patient records. Three feature selection techniques were studied along with 13 classical ML models using five-fold cross-validation. A stacking ML model was trained using the predictions of the three best-performing models for final classification. The stacking ML model provided an accuracy, precision, recall, specificity, F1-score, and area under the curve (AUC) of 89.41%, 90.10%, 89.41%, 87.83%, 89.28%, and 0.881, respectively. This indicates the effectiveness of the proposed model in predicting emergency readmissions. The healthcare providers can intervene pro-actively to reduce emergency hospital readmission risk and improve patient outcomes and decrease healthcare costs using the proposed model.

8.
Mol Ther Nucleic Acids ; 32: 553-565, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37215150

RESUMO

Gene editing using clustered regularly interspaced short palindromic repeats (CRISPR) targeted to HIV proviral DNA has shown excision of HIV from infected cells. However, CRISPR-based HIV excision is vulnerable to viral escape. Targeting cellular co-factors provides an attractive yet risky alternative to render viral escape irrelevant. Cyclin T1 is a critical modulator of HIV transcription and mediates recruitment of positive transcription elongation factor-b (P-TEFb) kinase for transcriptional elongation. Hence, a CRISPR-mediated cyclin T1 inactivation will silence HIV transcription, locking it in an inactive form in the cell and thereby serving as an effective antiviral and possibly effecting a functional cure. However, cellular genes play important roles, and their uncontrolled inhibition can promote undesirable effects. Here, we demonstrate a conditional inducible RNA polymerase II (RNA Pol II) mono-promoter-based co-expression of a CRISPR system targeting cyclin T1 from a single transcription unit. Co-expression of guide RNA (gRNA) and CRISPR-associated protein (Cas9) is observed only in HIV-infected cells and leads to sustained HIV suppression in stringent chronically infected cell lines as well as in T cell lines. We further show that incorporation of cis-acting ribozymes immediately upstream of the gRNA further enhances HIV silencing.

9.
Environ Sci Pollut Res Int ; 30(16): 47381-47393, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36738411

RESUMO

Though mass vaccination programs helped to reduce the severity of the ongoing pandemic, various unwanted effects were reported in Turkey and Bangladesh after taking vaccines. The purpose of this study was to evaluate and compare the adverse effects of several vaccines in Turkey and Bangladesh and how the population of both countries prioritizes the continuation of vaccination compared to the side effects. An online survey with a pretest was conducted to gather data over the research period from July 10, 2021 to December 10, 2021. Finally, the questionnaire was shared with the mass population of Turkey and Bangladesh who have received at least one or two doses of the COVID-19 vaccines. The quality of the questionnaire was evaluated with Cronbach's alpha test. The study consisted of 1508 respondents from Bangladesh and 602 respondents from Turkey. Among the total 2110 respondents, 50.0% were male 66.8% were from the 18-30 years age range, and 77.5% reported living in the city area. Among all the respondents, 64.99% of those vaccinated in Bangladesh and 67.28% of those vaccinated in Turkey reported side effects after vaccinations. Participants receiving mRNA vaccines (Pfizer and Moderna) experienced the most side effects, with many reporting pain at the injection site in both nations. Following that, fever, body pain, and headache were common in Bangladesh, whereas body pain, fatigue, and arm numbness were common in Turkey. The study found no significant adverse events reported in Turkey and Bangladesh following the first and second doses of COVID-19 vaccination. These COVID-19 vaccines showed similar patterns of efficacy and safety during the short period of analysis. Vaccines from different manufacturers showed a non-significant level of adverse events during this binational AEFI approach to COVID-19 vaccines. More studies are recommended on the efficacy and safety of several vaccines to discover unexpected effects.


Assuntos
COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Vacinas , Masculino , Humanos , Idoso , Feminino , Vacinas contra COVID-19/efeitos adversos , Autorrelato , Bangladesh , Turquia , COVID-19/prevenção & controle , Vacinação , Imunização , Dor
10.
Int J Breast Cancer ; 2022: 2599689, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35223101

RESUMO

The use of dietary phytochemical rather than conventional therapies to treat numerous cancers is now a well-known approach in medical science. Easily available and less toxic dietary phytochemicals present in plants should be introduced in the list of phytochemical-based treatment areas. Sesamin, a natural phytochemical, may be a promising chemopreventive agent aiming to manage breast cancer. In this study, we discussed the pharmacological properties of sesamin that determine its therapeutics opportunity to be used in breast cancer treatment and other diseases. Sesamin is available in medicinal plants, especially in Sesamum indicum, and is easily metabolized by the liver. To better understand the antibreast cancer consequence of sesamin, we postulate some putative pathways related to the antibreast cancer mechanism: (1) regulation of estrogen receptor (ER-α and ER-ß) activities, (2) suppressing programmed death-ligand 1 (PD-L1) overexpression, (3) growth factor receptor inhibition, and (4) some tyrosine kinase pathways. Targeting these pathways, sesamin can modulate cell proliferation, cell cycle arrest, cell growth and viability, metastasis, angiogenesis, apoptosis, and oncogene inactivation in various in vitro and animal models. Although the actual tumor intrinsic signaling mechanism targeted by sesamin in cancer treatment is still unknown, this review summarized that this phytoestrogen suppressed NF-κB, STAT, MAPK, and PIK/AKT signaling pathways and activated some tumor suppressor protein in numerous breast cancer models. Cotreatment with γ-tocotrienol, conventional drugs, and several drug carriers systems increased the anticancer potentiality of sesamin. Furthermore, sesamin exhibited promising pharmacokinetics properties with less toxicity in the bodies. Overall, the shreds of evidence highlight that sesamin can be a potent candidate to design drugs against breast cancer. So, like other phytochemicals, sesamin can be consumed for better therapeutic advantages due to having the ability to target a plethora of molecular pathways until clinically trialed standard drugs are not available in pharma markets.

11.
Biomed Res Int ; 2022: 7265445, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35968239

RESUMO

Scutellaria (Lamiaceae), which contains over 350 species, usually known as skullcaps, is found throughout Europe, the United States, and East Asia. In traditional Chinese medicine, several species are used to wipe out heat-evil and remove surface ills (TCM). The current study examines the ethnopharmacology, biological activity, and chemical substances associated with Scutellaria species. More than 295 chemicals, including flavonoids and diterpenes, have been identified. Scutellaria and its active principles have been shown in studies to have a wide range of pharmacological activities, including antioxidant, antimicrobial, antifeedant, phytotoxic, acaricidal toxicity, antibacterial, anti-inflammatory, and antianalgesic activities. Currently, effective monomeric compounds or active components from Scutellaria have been evaluated for pharmacological action in vivo and in vitro. More data facilitates applications and exploitation of novel medication development.


Assuntos
Lamiaceae , Óleos Voláteis , Scutellaria , Etnofarmacologia , Medicina Tradicional Chinesa , Óleos Voláteis/farmacologia , Scutellaria/química
12.
Environ Sci Pollut Res Int ; 29(31): 46385-46404, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35486279

RESUMO

Diabetes is a global health concern that has affected almost 415 million people globally. Bromocriptine is a dopamine D2 agonist, which is a Food and Drug Administration (FDA)-approved drug to treat type 2 diabetes mellitus (T2DM) patients. However, it is considered that a novel treatment therapy is required which can be used in the treatment of diabetes with or without other antidiabetic agents. Dopamine agonists are usually used in neurological disorders like Parkinson's disease (PD), restless leg syndrome, and hyperprolactinemia. However, dopamine agonists including bromocriptine and cabergoline are also effective in reducing the glycemic level in T2DM patients. Bromocriptine was formerly used for the treatment of PD, hyperprolactinemia, and restless leg syndrome, but now it is used for improving glycemic levels as well as reducing free fatty acids and triglycerides. In addition, cabergoline has been found to be effective in glycemic control, but this drug is yet to be approved by the FDA due to its limitations and lack of study. Findings of the clinical trials of bromocriptine have suggested that it reduces almost 0.4-0.8% glycated hemoglobin and cardiovascular risk by 40% in insulin-resistant patients. Moreover, the safe use of bromocriptine in obese T2DM patients makes it a more attractive option as it causes weight loss. Indeed, bromocriptine is a novel therapy for T2DM patients, as its mechanism of action is unique in T2DM patients with minimal adverse effects. This review summarizes the potential of dopamine agonists in the treatment of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperprolactinemia , Doença de Parkinson , Síndrome das Pernas Inquietas , Bromocriptina/farmacologia , Bromocriptina/uso terapêutico , Cabergolina/uso terapêutico , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Agonistas de Dopamina/farmacologia , Agonistas de Dopamina/uso terapêutico , Humanos , Hiperprolactinemia/induzido quimicamente , Hiperprolactinemia/tratamento farmacológico , Síndrome das Pernas Inquietas/induzido quimicamente , Síndrome das Pernas Inquietas/tratamento farmacológico
13.
Environ Sci Pollut Res Int ; 29(19): 29130-29140, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34997511

RESUMO

Obesity is a multifaceted disease encompassing deposition of an unnecessary amount of fat which upsurges the possibility of other complications, viz., hypertension and certain type of cancers. Although obesity results from combination of genetic factors, improper diet and inadequate physical exercise also play a major role in its onset. The present study aims at exploring the anti-obesity activity of Crinum latifolia leaf extract in obese rats. The leaves were extracted using hydroalcoholic extraction which was later diluted with water and given to obese rats. The dosing was started from the 4th week (by oral administration of extract of Crinum latifolia (100 mg/kg and 200 mg/kg) and combination of Crinum latifolia leaf extract 200 mg/kg and orlistat 30 mg/kg) till the 10th week. Various angiogenic, antioxidant, biochemical, and inflammatory biomarkers were assessed at the end of the study. The obese symptoms were progressively reduced in treatment groups when compared to disease control groups. The angiogenic parameters and inflammatory parameters were consequently reduced in treatment groups. The oxidative parameters superoxide dismutase (SOD) and catalase were gradually increased, while levels of TBARS were reduced in treatment groups showing antioxidant nature of leaf hydroalcoholic extract. The Crinum latifolia leaf extract possesses anti-obesity properties and therefore can be used as a therapeutic option in the management of obesity.


Assuntos
Crinum , Animais , Antioxidantes/farmacologia , Crinum/química , Obesidade , Estresse Oxidativo , Extratos Vegetais/química , Ratos
14.
Adv Pharmacol Pharm Sci ; 2022: 3169500, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265845

RESUMO

Background: Polyherbal formulations (PLFs) have been widely used for liver protection, treatment for hepatic dysfunction, and regeneration. They can also enhance appetite and protect the gastrointestinal tract from injury. In spite of the prevalent use, there is a need of scientific evidence on their effectiveness and safety. The objective of the present study was to assess the hepatoprotective effect of polyherbal formulations (commercially available in Bangladesh namely Heptaliv, Holyliv, Icturn, and J-deenar) in CCl4-induced hepatotoxicity in mice. Methods: In this study, Swiss albino mice were treated for 7 days with distilled water or PLFs (2.6 and 5.2 ml/kg body weight/day, per os.) followed by single subcutaneous injection of CCl4 (1 ml/kg body weight, diluted with olive oil in 1 : 1 ratio) on day 8. Twenty-four hours after CCl4 administration, the mice were monitored for the effects of PLFs on liver morphology, biochemical parameters including serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), and total bilirubin. Phenobarbitone-induced sleeping time and histopathology changes in liver tissues were also monitored. Results: CCl4 administration caused significant hepatotoxicity as evidenced by marked elevation in AST, ALT, ALP, and total bilirubin. Phenobarbitone-induced sleeping time and infiltration of inflammatory cells and centrizonal necrosis on histological examination of liver demonstrated hepatic injury after CCl4 administration. However, the administration of Icturn and J-deenar polyherbal formulations at the higher dose significantly decreased the levels of AST, ALT, ALP, and total bilirubin. Moreover, pentobarbitone-induced sleeping time and histopathological analysis also revealed significant improvement as result of treatment with formulations Icturn and J-deenar. Conclusion: Our results confirmed that polyherbal formulations (Icturn and J-deenar) can significantly prevent CCl4-induced hepatotoxicity in mice, demonstrating their protective effect for liver.

15.
J Oncol ; 2022: 9396760, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36284633

RESUMO

Cancer has been one of the most dominant causes of mortality globally over the last few decades. In cancer treatment, the selective targeting of tumor cells is indispensable, making it a better replacement for conventional chemotherapies by diminishing their adverse side effects. While designing a drug to be delivered selectively in the target organ, the drug development scientists should focus on various factors such as the type of cancer they are dealing with according to which drug, targeting moieties, and pharmaceutical carriers should be targeted. All published articles have been collected regarding cancer and drug-targeting approaches from well reputed databases including MEDLINE, Embase, Cochrane Library, CENTRAL and ClinicalTrials.gov, Science Direct, PubMed, Scopus, Wiley, and Springer. The articles published between January 2010 and December 2020 were considered. Due to the existence of various mechanisms, it is challenging to choose which one is appropriate for a specific case. Moreover, a combination of more than one approach is often utilized to achieve optimal drug effects. In this review, we have summarized and highlighted central mechanisms of how the targeted drug delivery system works in the specific diseased microenvironment, along with the strategies to make an approach more effective. We have also included some pictorial illustrations to have a precise idea about different types of drug targeting. The core contribution of this work includes providing a cancer drug development scientist with a broad preliminary idea to choose the appropriate approach among the various targeted drug delivery mechanisms. Also, the study will contribute to improving anticancer treatment approaches by providing a pathway for lesser side effects observed in conventional chemotherapeutic techniques.

16.
Curr Pharm Des ; 27(22): 2635-2647, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33463452

RESUMO

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder that significantly affects cognitive functions in a way that causes loss of memory, thinking, and behavior. Multiple studies revealed that neuroinflammation associated with AD is linked with the amyloid-beta deposition in the brain. Elevated levels of expression of cytokines, microglial activation, nuclear factor kappa B, and reactive oxygen species play roles in AD-related inflammatory processes. Indeed, effective therapeutic approaches are urgently required to develop therapeutic agents to prevent and treat AD. So far, many anti-AD drug candidates have failed in the clinical stages and currently available drugs only provide symptomatic treatment. In recent times, pharmacologically active phytochemicals have been found to possess promising anti-neuroinflammatory effects; therefore, these natural products can be useful in AD treatment. In this review, we have comprehensively discussed the role of neuroinflammation and the molecular processes altered by multiple steroid and terpenoid-derived phytochemicals in various AD-related neuroinflammatory pathways. Indeed, steroid and terpenoid-derived phytochemicals show important therapeutic activities, which can be useful in ameliorating and treating AD-related neurodegeneration.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Esteroides , Terpenos/farmacologia
17.
Curr Pharm Des ; 27(38): 4017-4029, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34126892

RESUMO

Monoamine oxidases (MAOs) are a family of flavin adenine dinucleotide-dependent enzymes that have a crucial role in the metabolism of neurotransmitters of the central nervous system. Impaired function of MAOs is associated with copious brain diseases. The alteration of monoamine metabolism is a characteristics feature of aging. MAO plays a crucial role in the pathogenesis of Alzheimer's disease (AD), a progressive neurodegenerative disorder associated with an excessive accumulation of amyloid-beta (Aß) peptide and neurofibrillary tangles (NFTs). Activated MAO plays a critical role in the development of amyloid plaques from Aß as well as the formation of the NFTs. In the brain, MAO mediated metabolism of monoamines is the foremost source of reactive oxygen species formation. The elevated level of MAO-B expression in astroglia has been reported in the AD brains adjacent to amyloid plaques. Increased MAO-B activity in the cortical and hippocampal regions is associated with AD. This review describes the pathogenic mechanism of MAOs in aging as well as the development and propagation of Alzheimer's pathology.


Assuntos
Doença de Alzheimer , Envelhecimento , Peptídeos beta-Amiloides , Humanos , Monoaminoxidase , Emaranhados Neurofibrilares
18.
Artigo em Inglês | MEDLINE | ID: mdl-34194526

RESUMO

Acanthus ilicifolius Linn. (Acanthaceae) is a popular mangrove ethnomedicinal plant that cures several ailments, including asthma, diabetes, cancer, and many others. Our experiment was aimed at evaluating the anti-atherogenic effect of A. ilicifolius (leaf and stem) on a high-fat diet-induced atherogenic rat model. Atherosclerosis was developed in 12 weeks. Treatment with the standard drug (3 mg/kg b.w./day, p.o. of Simvastatin), separate doses of methanolic and ethanolic extracts of A. ilicifolius leaf (250 and 500 mg/kg b.w./day, p.o.), and stem (200 and 400 mg/kg b.w./day, p.o.) was subsequently conducted for additional 15 days. The anti-atherogenic effect was evaluated by estimating the change in body weight, systolic blood pressure, and lipid profile. Histopathology of aorta, liver, and kidney of atherogenic models was done for further evaluation. The antioxidant effect of different extracts was performed via DPPH (2,2-diphenyl-1-picrylhydrazyl) assay using ascorbic acid as standard. The anticoagulant effect was determined after 15 days of treatment with the same doses of the plant extracts and the standard Warfarin (2 mg/kg b.w./day, p.o.). When compared with atherogenic control, treatment with A. ilicifolius significantly reduced (p < 0.01) body weight, systolic blood pressure, and serum lipid levels while it elevated HDL (high-density lipoprotein) level in a dose-dependent manner. Moreover, bleeding and clotting time was significantly decreased (p < 0.01) under the treatment of plant extracts. The histopathological data showed considerable improvement in tissue morphology after treatment. Our study evidenced that the alcoholic extracts of A. ilicifolius leaf and stem have anti-atherogenic properties and may be recommended as a potential herbal remedy for preventing cardiovascular diseases.

19.
Biomed Res Int ; 2021: 8844030, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33644232

RESUMO

Dendrimers are nanosized, symmetrical molecules in which a small atom or group of atoms is surrounded by the symmetric branches known as dendrons. The structure of dendrimers possesses the greatest impact on their physical and chemical properties. They grow outwards from the core-shell which further reacts with monomers having one reactive or two dormant molecules. Dendrimers' unique characteristics such as hyperbranching, well-defined spherical structure, and high compatibility with the biological systems are responsible for their wide range of applications including medical and biomedical areas. Particularly, the dendrimers' three-dimensional structure can incorporate a wide variety of drugs to form biologically active drug conjugates. In this review, we focus on the synthesis, mechanism of drug encapsulations in dendrimers, and their wide applications in drug delivery.


Assuntos
Dendrímeros/química , Dendrímeros/uso terapêutico , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Humanos
20.
Pharmacy (Basel) ; 9(2)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065255

RESUMO

Background: This fact-finding study aimed to attain an overall idea and knowledge about medicine disposal practices in Dhaka Metropolitan households. Methods: This mixed study (both quantitative and qualitative) was orchestrated to inspect the household leftover medicine disposal pattern's governing status. A cross-sectional survey was conducted following a structured questionnaire and key informant interview with a household person and in-depth interviews with the top pharmaceutical and government officials. Results: Findings disclose that, for most of the key informants, the terms "drug disposal" and "drug pollution" were unknown; more precisely, 67% and 74% of key informants even did not hear these two terms. Almost all (87%) households faced undesired incidents due to the insecure storage of medicines. People disposed of excess and expired medication in regular dustbins (47%), threw out of the window (19%), flushed within commode (4%), burnt in fire (2%), and reused (4%). A good percentage of people (21%) returned unexpired drugs to the pharmacy and bought other medicines on a need basis. A total of 72% wanted a medicine take-back program, and 100% agreed on mass education on this issue. Officials of pharmaceuticals conferred mixed opinion: top-ranked pharmaceuticals will adopt leftover medicine disposal practices; middle and low-ranked pharmaceutical companies are reluctant, merely denied mentioning the less important issue. Conclusions: The absence of mass awareness and standard laws and policies may explain these existing aberrant practices.

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