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INTRODUCTION: The completion of the Human Genome Project in 2003 marked the beginning of a transformative era in medicine. This milestone laid the foundation for personalized medicine, an innovative approach that customizes healthcare treatments. CONTENT: Central to the advancement of personalized medicine is the understanding of genetic variations and their impact on drug responses. The integration of artificial intelligence (AI) into drug response trials has been pivotal in this domain. These technologies excel in handling large-scale genomic datasets and patient histories, significantly improving diagnostic accuracy, disease prediction and drug discovery. They are particularly effective in addressing complex diseases such as cancer and genetic disorders. Furthermore, the advent of wearable technology, when combined with AI, propels personalized medicine forward by offering real-time health monitoring, which is crucial for early disease detection and management. SUMMARY: The integration of AI into personalized medicine represents a significant advancement in healthcare, promising more accurate diagnoses, effective treatment plans and innovative drug discoveries. OUTLOOK: As technology continues to evolve, the role of AI in enhancing personalized medicine and transforming the healthcare landscape is expected to grow exponentially. This synergy between AI and healthcare holds great promise for the future, potentially revolutionizing the way healthcare is delivered and experienced.
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Inteligência Artificial , Medicina de Precisão , HumanosRESUMO
Partial and full PPAR-γ agonists have shown promising effects and antihypertensive and antidiabetic agents through increased plasma adiponectin concentration. This study is aimed at examining the role of PPAR-γ, alpha-adrenoceptors, and adiponectin receptors in the modulation of vasopressor responses to angiotensin II (Ang II) and adrenergic agonists, after a subset treatment of partial and full PPAR-γ agonists, each individually, and also when coupled with adiponectin in SHRs. The antioxidant potential and metabolic indices for these animals were also determined. Group I (WKY) and group II (SHR) were designated as normotensive control and hypertensive control, respectively. Groups III (SHR) and IV (SHR) received irbesartan (30 mg/kg) and pioglitazone (10 mg/kg) orally for 28 days, and groups V (SHR), VI (SHR), and VII (SHR) were treated with adiponectin (2.5 µg/kg) intraperitoneally alone, in combination with irbesartan, and in combination with pioglitazone, respectively, from days 21 to 28 only. On day 29, sodium pentobarbitone (60 mg/kg) was used to anesthetize all test animals, and systemic hemodynamic and plasma adiponectin concentrations and in vitro and in vivo antioxidant potential were measured. As compared to the WKY control, the SHR control group's noninvasive blood pressure and basal mean arterial pressure were significantly greater, along with increased arterial stiffness, lower plasma nitric oxide, adiponectin concentration, and antioxidant enzyme levels (all P < 0.05). However, they were gradually normalized by single drug treatments in all groups, and to a greater extent in the SHR + Irb + Adp group (P < 0.05). In the acute study, the dose dependant mean arterial pressure responses to intravenously administered adrenergic agonists and angiotensin-II were significantly larger in SHRs as compared to WKY by 20-25%. Adiponectin alone and in combination significantly blunted vasopressor responses to these alpha-adrenergic agonists in the SHR + Pio + Adp group by 63%, whereas attenuated responses to ANG-II administration to 70% in SHR + Irb + Adp. In conclusion, the combined treatment of adiponectin with PPAR-agonists reduced the systemic vascular responses to adrenergic agonists and improved arterial stiffness. This an evidence of the interaction of adiponectin receptors, PPAR-γ, alpha-adrenoceptors, and ANG-II in the systemic vasculature of SHRs. A significant level of synergism has also been proved among full PPAR-γ agonists and adiponectin receptors.
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As we learn to co-exist with COVID-19, this Research Topic highlights significant research contributions that examine the interaction of COVID-19 and the social determinants of health. To emphasize the impactful research in this area, this Research Topic features scholarly contributions in the fields of Epidemiology, specifically Aging and Life-course Epidemiology, and Public Health, specifically Public Health Policy. This theme is intentionally broad in scope, and our editorial provides an overview of the key findings of the papers published in the Research Topic on COVID-19 pandemic and the social determinants of health. The types of articles received in response to this Research Topic are summarized below.
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Hepatotoxin carbon tetrachloride (CCl4) causes liver injury. This research aims to create ZnO-NPs using green synthesis from Moringa oleifera (MO) leaves aqueous extract, and chemically prepared and confirming the synthesis by specialized equipment analysis. The sizes formed of ZnO-NPs were 80 and 55 nm for chemical and green methods, respectively. In addition, to study their ability to protect Wistar Albino male rats against oxidative stress exposed to carbon tetrachloride. MO leaf aqueous extract, green synthesized ZnO-NPs, and ZnO-NPs prepared chemically at 100 and 200 mg/kg BW per day were investigated for their hepatoprotective effects on liver enzyme biomarkers, renal biomarkers, antioxidant enzymes, lipid peroxidation, hematological parameters, and histopathological changes. Compared to the control group, all liver and kidney indicators were considerably elevated after the CCl4 injection. However, the activity of antioxidant enzymes in the liver was significantly reduced after the CCl4 injection. These outcomes indicate that MO leaf aqueous extract, greenly synthesized ZnO-NPs, and ZnO-NPs chemically prepared can restore normal liver and kidney function and activity, as well as hematological and antioxidant enzymes. The highest impact on enhancing the hepatoprotective effect was recorded for rats that received green synthesized ZnO-NPs. The increased drug delivery mechanism of green synthesized ZnO-NPs resulted in a higher protective effect than that of MO leaf aqueous extract.
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Previously, we found by constructing various luciferase reporters that a well-conserved ATF6-binding element in the CRELD2 promoter is activated by transient ATF6 overexpression. In this study, we established ATF6-deficient and ATF4-deficient cell lines to analyze CRELD2 mRNA and protein expression together with that of other ER stress-inducible factors. Our results showed that ATF6 deficiency markedly suppressed tunicamycin (Tm)-induced expression of unglycosylated CRELD2. This reduction reflected a decrease in the CRELD2 transcription level. On the other hand, a putative ATF4-binding site in the mouse CRELD2 promoter did not respond to Tm stimulation, but ATF4 loss resulted in reductions in CRELD2 mRNA and protein expression, accompanied by a decrease in Tm-induced ATF6 expression. In contrast, transient suppression of GADD34, an ATF4 downstream factor, suppressed Tm-induced CRELD2 protein expression without a decrease in ATF6 protein expression. Furthermore, we investigated the association of CRELD2 with a well-known ERAD substrate, namely, an α1-antitripsin truncation mutant, NHK, by generating various CRELD2 and NHK constructs. Coimmunoprecipitation of these proteins was observed only when the cysteine in the CXXC motif on the N-terminal side of CRELD2 was replaced with alanine, and the interaction between the two was found to be disulfide bond-independent. Taken together, these findings indicate that CRELD2 expression is regulated by multiple factors via transcriptional and posttranscriptional mechanisms. In addition, the N-terminal structure of CRELD2, including the CXXC motif, was suggested to play a role in the association of the target proteins. In the future, the identification and characterization of factors interacting with CRELD2 will be useful for understanding protein homeostasis under various ER stress conditions.
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Background: Camel meat tainted with heavy metals or trace elements may pose a health risk to consumers. Heavy metal contamination poses a severe danger due to both their toxicity and bioaccumulation in the food chain. Aim: To estimate the residual levels of heavy metals (Co, Cr, Mn, Se, and As) in muscle, liver, kidney, hair, and serum of three camel breeds (Magaheem, Maghateer, and Wadha) collected from Al-Omran abattoir, Al-Ahsa, Saudi Arabia. Methods: A total of 225 tissue samples (muscles, liver, kidney, serum, and hair) were taken and analyzed using an Atomic Absorption Spectrophotometer. Health risk assessment was assessed using the guidelines set by the US Environmental Protection Agency. Results: Camel breed significantly (p < 0.05) influences Co, Cr, Mn, and Se accumulation and distribution in organs and muscle; however, arsenic accumulation was not significantly affected (p < 0.05) by camel breeds. The highest values of Co, Cr, Se, and Mn in all examined samples were detected in the liver samples of Maghateer and Magaheem breeds. Furthermore, significant strong positive correlation between serum and liver cobalt, chromium, manganese, and arsenic. The estimated daily intake owing to camel meat consumption was less than the tolerated daily intake. Conclusion: Heavy metals were distributed among different breeds of camel. Trace elements (Pb and Cd) in meat and offal were below the international maximum permissible limit. The correlation between samples reflects the role of hair as a good tool for the identification of heavy metal pollution.
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Arsênio , Metais Pesados , Oligoelementos , Estados Unidos , Animais , Camelus , Metais Pesados/análise , Carne , Músculos/química , Medição de Risco , Cabelo/químicaRESUMO
This study was performed to reveal the risk factors associated with mortality in people living with HIV (PLHIV) who were diagnosed with COVID-19. Studies reporting deaths among PLHIV and infected with SARS-CoV-2 were investigated. After protocol setup and registration, the extracted sources were categorized and assessed for quality. This study examined ten articles with a total of 46,136 patients. Patients aged ≥ 60 years (hazard ratio [HR] = 2.22; 95% CI: 1.617, 3.050; p < 0.001), male (HR = 1.668; 95% CI: 1.179, 2.361; p = 0.004), and people with diabetes (risk ratio [RR] = 3.34; 95% CI: 1.45, 7.68; p = 0.005) were at higher risk of death. Adherence to antiretroviral therapy (ART) reduced mortality risk (RR = 0.90; 95% CI: 0.83, 0.98; p = 0.02). Patients in the survival groups showed a statistically significant lower mean of C-reactive protein (mean difference = 114.08; 95% -74.05, 154.10; p < 0.001). Deceased patients showed higher mean levels of interleukin-6 (IL-6). Chronic respiratory disorders, hypertension, oxygen requirement, admission to an intensive care unit, D-dimer levels, and HIV viral load < 50 copies RNA/mL before admission did not show statistically significant differences between the deceased and survival groups. ART therapy reduced mortality risk (RR = 0.90; 95% 0.83, 0.98; p = 0.02). Identifying PLHIV at higher mortality risk could improve the outcomes of COVID-19 by stratifying these patients to the most effective treatment in a timely fashion.
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COVID-19 , Infecções por HIV , Humanos , Masculino , COVID-19/complicações , Infecções por HIV/complicações , SARS-CoV-2 , Fatores de Risco , Resultado do TratamentoRESUMO
Introduction: Avian orthoavulavirus-1 (AOAV1) has a wide host range, including domestic and wild birds. The present study aimed to identify the currently circulating AOAV1 strains from some outbreaks in some backyard pigeons in the eastern region of Saudi Arabia (ERSA). Methods: Tracheal/cloacal swabs and tissue specimens were collected from eight backyards in Al-Ahsa, ERSA, between January 2021 and March 2023. Samples were tested for the presence of AOAV1 using commercial real-time RT-PCR. Part of the fusion gene was also amplified by gel-based RT-PCR, and the obtained amplicons were sequenced. Results and discussion: AOAV1 was detected in samples from the eight flocks. The retrieved sequences from samples of 6/8 pigeon backyards are reported. Phylogenetic analysis based on the obtained sequences from these backyard pigeons showed the segregation of the obtained sequences in AOAV1 genotypes VI.2.1 and VII.1.1. Clinically, nervous manifestations were dominant in pigeons infected with both genotypes. Respiratory manifestations and significantly higher overall mortality rate were induced by genotype VI.2.1. The deduced amino acid sequences of the fusion protein cleavage site (FPCS) showed that all the detected isolates belong to velogenic strains. Differences in clinical profiles induced by the natural infection of pigeons with AOAV1 genotypes VI.2.1 and VII.1.1 were reported. The present findings highlight the potential roles of some backyard pigeons in the long-distance spread and cross-species transmission of the reported AOAVI genotypes. Further research is required to perform biotyping and pathotyping of the reported strains.
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Cryptosporidium is an intestinal protozoan that cause diarrhea in livestock all over the world and have zoonotic importance. The present study aimed to determine the prevalence of Cryptosporidium spp. in horses in Egypt and evaluate the associated risk factors. A total of 420 fecal samples were collected from three governorates (Giza, Kafr ElSheikh and Qalyubia) and examined microscopically using Ziehl-Neelsen staining method. The overall prevalence of Cryptosporidium spp. was 29% and Kafr ElSheikh governorate had the highest rate in comparison to other areas. The prevalence of Cryptosporidium spp. in examined horses had significant association with sex, age, type of management, absence of bedding and presence of dogs. The higher prevalence rate was observed in females (32.2%), age group less than two years (43.2%), mixed (grazing and stable) horses (36.1%), animals had history of diarrhea (33%), absence of bedding (35.1%) and contact with dogs (35.7%). These findings give baseline data for further research. It is necessary to establish control strategy for Cryptosporidium spp. infection in order to lower the risk of infection in animals and human.
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Criptosporidiose , Cryptosporidium , Feminino , Animais , Humanos , Cães , Cavalos , Pré-Escolar , Criptosporidiose/epidemiologia , Prevalência , Egito/epidemiologia , Fatores de Risco , Fezes , Diarreia/epidemiologia , Diarreia/veterinária , GadoRESUMO
This meta-analysis aims to investigate demographic disparities in monkeypox (mpox) infections among various groups based on ethnicity, sexual partners, and gender. The study includes data from 2,646 to 4,002 patients across various outcomes. Among racial demographics, black populations show a lower odds ratio for mpox compared to white populations (OR=0.08 [0.01, 0.45], 95% CI, p=0.004). However, no statistically significant difference is found when comparing black populations with Hispanic or Asian populations (OR=0.72 [0.46, 1.11], p=0.13). There was a substantial disparity between gay, bisexual and other men-who-have-sex-with-men (GBMSM) and heterosexual populations, with significantly higher odds of mpox among the former (OR=393.80, 95% CI: [82.45, 180.85], p<0.00001). Analysis of sexual partners indicates a significant difference in infection risk between individuals with zero to one sexual partner and those with more than two partners (OR=0.06 [0.01, 0.28], p=0.0005). Additionally, there is a substantial difference in infection risk between male and female populations (OR=3868.02, p<0.00001). These findings emphasize the importance of considering demographic factors in understanding mpox transmission and risk profiles. Targeted research and intervention strategies are required to address the identified disparities and mitigate the spread of mpox.
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Mpox , Minorias Sexuais e de Gênero , Humanos , Feminino , Masculino , Homossexualidade Masculina , DemografiaRESUMO
Inflammation drives coronary artery disease and atherosclerosis implications. Lipoprotein entry, retention, and oxidative modification cause endothelial damage, triggering innate and adaptive immune responses. Recruited immune cells orchestrate the early atherosclerotic lesions by releasing proinflammatory cytokines, expediting the foam cell formation, intraplaque haemorrhage, secretion of matrix-degrading enzymes, and lesion progression, eventually promoting coronary artery syndrome via various inflammatory cascades. In addition, soluble mediators disrupt the dynamic anti- and prothrombotic balance maintained by endothelial cells and pave the way for coronary artery disease such as angina pectoris. Recent studies have established a relationship between elevated levels of inflammatory markers, including C-reactive protein (CRP), interleukins (IL-6, IL-1ß), and tumour necrosis factor-alpha (TNF-α) with the severity of CAD and the possibility of future cardiovascular events. High-sensitivity C-reactive protein (hs-CRP) is a marker for assessing systemic inflammation and predicting the risk of developing CAD based on its peak plasma levels. Hence, understanding cross-talk interactions of inflammation, atherogenesis, and CAD is highly warranted to recalculate the risk factors that activate and propagate arterial lesions and devise therapeutic strategies accordingly. Cholesterol-inflammation lowering agents (statins), monoclonal antibodies targeting IL-1 and IL-6 (canakinumab and tocilizumab), disease-modifying antirheumatic drugs (methotrexate), sodium-glucose transport protein-2 (SGLT2) inhibitors, colchicine and xanthene oxidase inhibitor (allopurinol) have shown promising results in reducing inflammation, regressing atherogenic plaque and modifying the course of CAD. Here, we review the complex interplay between inflammatory, endothelial, smooth muscle and foam cells. Moreover, the putative role of inflammation in atherosclerotic CAD, underlying mechanisms and potential therapeutic implications are also discussed herein.
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Aterosclerose , Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Proteína C-Reativa , Interleucina-6 , Células Endoteliais/metabolismo , Aterosclerose/metabolismo , Inflamação/complicações , Inflamação/tratamento farmacológicoRESUMO
A new series inspired by combining fragments from nitazoxanide (NTZ) and 4-aminosalicylic acid (4-ASA) was synthesized and screened for in vitro antibacterial and antimycobacterial activities. The majority showed higher antibacterial potency than NTZ against all the screened strains, notably, 5f, 5j, 5n and 5o with MICs of 0.87-9.00 µM. Compounds 5c, 5n and 5o revealed higher potency than ciprofloxacin against K. pneumoniae, while 5i was equipotent. For E. faecalis, 3b, 5j, and 5k showed higher potency than ciprofloxacin. 5j was more potent against P. aeruginosa than ciprofloxacin, while 5n was more potent against S. aureus with an MIC of 0.87 µM. 5f showed equipotency to ciprofloxacin against H. pylori with an MIC of 1.74 µM. Compounds 3a and 3b (4-azidoNTZ, MIC 4.47 µM) are 2 and 5-fold more potent against Mycobacterium tuberculosis (Mtb H37Rv) than NTZ (MIC 20.23 µM) and safer. 4-Azidation and/or acetylation of NTZ improve both activities, while introducing 1,2,3-triazoles improves the antibacterial activity. Molecular docking studies within pyruvate ferredoxin oxidoreductase (PFOR), glucosamine-6-phosphate synthase (G6PS) and dihydrofolate reductase (DHFR) active sites were performed to explore the possible molecular mechanisms of actions. Acceptable drug-likeness properties were found. This study may shed light on further rational design of substituted NTZ as broad-spectrum more potent antimicrobial candidates.
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Increased production and buildup of reactive oxygen species (ROS) can lead to various health issues, including metabolic problems, cancers, and neurological conditions. Our bodies counteract ROS with biological antioxidants such as SOD, CAT, and GPx, which help prevent cellular damage. However, if there is an imbalance between ROS and these antioxidants, it can result in oxidative stress. This can cause genetic and epigenetic changes at the molecular level. This review delves into how ROS plays a role in disorders caused by oxidative stress. We also look at animal models used for researching ROS pathways. This study offers insights into the mechanism, pathology, epigenetic changes, and animal models to assist in drug development and disease understanding.
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Introduction: Bovine viral diarrhea virus (BVDV) brings great economic loss to the cattle industry worldwide. Developing a control/prevention strategy requires the prior assessment of certain epidemiological parameters. To determine the BVD incidence rate and associated risk factors, a dairy cattle herd in the eastern region of Saudi Arabia was monitored between 2020 and 2022. Methods: Nasal swabs (n = 190), rectal swabs (n = 190), and sera (n = 190) were collected from 79 cows in this herd. Collected sera and swabs were tested using the commercially available ELISAs for the BVDV antibodies and antigens, respectively. Collected sera were also tested for the presence of BVDV nucleic acids using commercial real-time RT-PCR kits. Results and discussion: Our data show BVDV seroprevalence (18.8%, 15%, and 8.2%) in the tested animals in 2020-2022, respectively. None of the collected nasal swabs, rectal swabs, or sera tested positive for the BVDV antigen, whereas 10.1%, 10%, and 18.1% of the tested sera were positive for BVDV nucleic acid in 2020-2022, respectively. The incidence rate was estimated at 0.02446 new cases/year despite the detection of BVDV in seronegative animals on single or two occasions at ≥6-month intervals. Young calves and bulls remained apparently unexposed to BVDV despite their presence with BVDV-infected females, with no significant physical separation. Both seropositivity and nucleic acid detectability showed significant positive and negative correlations, respectively, with reproductive performance. Collectively, the present study provides useful clues about the transmissibility of BVDV in the presence of possibly persistently infected animals. To the best of our knowledge, this is the first longitudinal study of BVDV in the Eastern Region of Saudi Arabia. Further detailed characterization of the circulating BVDVs is encouraged.
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Rift Valley fever (RVF) is a mosquito-borne viral disease that affects a variety of domestic animals, including cattle, sheep, goats, and camels, and has zoonotic potential. Although the rift valley fever virus (RVFV) is usually asymptomatic in camels, it can induce abortion in some pregnant animals. In the current study, a serosurvey was carried out to investigate the prevalence of RVFV antibodies and related risk factors in camels from four Egyptian governorates. A total of 400 serum samples were examined for anti-RVFV antibodies using a competitive enzyme-linked immunosorbent assay (c-ELISA). The results revealed that the overall prevalence of RVF among examined camels was 21.5% and the disease was more prevalent in Kafr ElSheikh governorate in Nile Delta of Egypt. In addition, the age group of camels with more than 5 years (OR=4.49, 95%CI: 1.39-14.49), the female sex (OR=3.38, 95%CI: 1.51-7.58), the emaciated animals (OR=1.52, 95%CI: 0.86-2.66), the summer season's infection (OR=5.98, 95%CI: 1.79-19.93), the presence of mosquitoes (OR= 2.88, 95%CI: 1.39-5.95), and the absence of mosquitoes control (OR=3.97, 95%CI: 2.09-7.57) were identified as risk factors for RVFV infection. The results of this study support knowledge on the risk factors for RVFV infection and demonstrate that camels raising in Egypt have RVFV antibodies. Quarantine measures or vaccination program should be implemented to reduce the likelihood of RVFV introduction, dissemination among susceptible animals, and ultimately transmission to humans.
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Doenças dos Bovinos , Doenças das Cabras , Febre do Vale de Rift , Vírus da Febre do Vale do Rift , Doenças dos Ovinos , Humanos , Gravidez , Bovinos , Animais , Feminino , Ovinos , Camelus , Egito/epidemiologia , Estudos Soroepidemiológicos , Febre do Vale de Rift/epidemiologia , Cabras , Anticorpos Antivirais , Doenças dos Bovinos/epidemiologia , Doenças das Cabras/epidemiologia , Doenças dos Ovinos/epidemiologiaRESUMO
Background and Aim: Avian viral diseases usually cause high economic losses because of high morbidity and mortality and poor growth. The rearing of chickens in backyards could have an important role in the spread of certain diseases, particularly those of viral origin. Infected birds might be prone to many viral infections for several reasons, including a lack of vaccination programs, the mixing of different bird species in the same location, and the close interactions of these birds with wild and migratory birds carrying various pathogens. This study aimed to conduct serological surveillance of avian encephalomyelitis virus (AEV) in some backyard chickens in the eastern region of Saudi Arabia. Materials and Methods: Serum samples (n = 368) were collected from domestic chickens reared in 10 backyards in the Eastern Province of Saudi Arabia. None of the domestic birds in these 10 backyards were vaccinated against the virus. In addition, 78 serum samples were collected from free-ranging birds belonging to Columbidae, such as pigeons and doves, in common areas near the domestic backyards. We tested these sera for specific antibodies against AEV. Results: Our results revealed seroconversion to AEV among the examined chickens (14.6%). None of the tested pigeons and doves displayed seroconversion to AEV. Conclusion: Seroconversion of these non-vaccinated birds against AEV was suggestive of a recent natural infection by this virus. Further studies with a large number of birds are required to molecularly characterize the circulating strains of this virus in this area.
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HIV is a global deliberating infectious disease. Of note, more than 36 million people living with HIV (PLHIV) with approximately newly diagnosed 1.5 million cases annually. M184V is a single base mutation in the highly conserved YMDD domain of reverse transcriptase (RT). It is one of the most encountered resistances associated with mutations to nucleoside RT inhibitors. There were continuous efforts to evaluate the impact of M184V mutation on the treatment outcomes in PLHIV. Therefore, the present systematic review was executed to reveal the virological failure, virological suppression, and resistance to antiretroviral therapy (ART) regimens in PLHIV with the M184V mutation. All clinical studies comparing the treatment outcomes among PLHIV harboring or not harboring M184V mutation were appropriate for systematic review and meta-analysis. The present systematic review included six articles, encompassing 4760 PLHIV. Of them, 1222 (25.67%) patients had M184V mutation, while 3538 (74.32%) PLHIV did not. The meta-analysis showed that patients with M184V mutation were 1.87 times more liable to virological failure (risk ratio [RR] 1.87; 95% 1.09, 3.20; p = 0.02). Furthermore, pooling the data from two studies revealed a significantly higher risk of viral blips (RR 2.26; 95% 1.47, 3.46; p = 0.0002). Concerning discontinuation of ART, there was no statistical difference between patients with and without M184V mutation (RR: 0.99; 95% 0.78, 1.25; p = 0.90). The present study revealed the negative impact of the M184V mutation on treatment outcomes in PLHIV. This included a higher risk of virological failure and viral blips, relative to patients without the mutation. Such patients may benefit from more aggressive and combined therapy for better disease management.
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Humanos , Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , HIV-1/genética , Resultado do Tratamento , Mutação , Farmacorresistência Viral/genética , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacologia , Transcriptase Reversa do HIV/genética , Transcriptase Reversa do HIV/uso terapêuticoRESUMO
Cisplatin is a cancer medication widely used today, but it still poses some problems due to its toxic properties in the body. To overcome this issue, a new complex has been developed as a potential anticancer drug prospect by minimizing its toxic consequences. A novel Zn(II)IleDTC complex containing isoleucine dithiocarbamate ligands has been produced and analyzed using a range of analytical and spectroscopic methods. The Zn(II) IleDTC complex were characterized using various methods, including UV-Vis spectroscopy, FT-IR, determination of melting point, conductivity, and HOMO-LUMO analysis. Furthermore, computational NMR spectrum analysis was conducted in this study. Molecular docking studies was conducted to evaluate the potential of Zn(II) isoleucine dithiocarbamate as an HIF1 inhibitor. The results showed that the Zn complex exhibited a good docking score of -6.6 and formed hydrogen bonds with ARG 17, VAL264, and GLU15, alkyl bonds with TRP27 and LEU32, and Pi-Alkyl bonds with PRO41 and ARG44. This suggests that the Zn(II) isoleucine dithiocarbamate complex could be a promising candidate for cancer treatment with potential HIF1 inhibition properties. To assess the dynamic stability and efficacy of protein-ligand interactions over time, molecular dynamics simulations was conducted for both individual proteins and protein complexes. The cytotoxicity evaluation of Zn(II) isoleucine dithiocarbamate against MCF-7 cells obtained an IC50 value of 362.70 µg/mL indicating moderate cytotoxicity and morphological changes of cancer cells causing cancer cells to undergo apoptosis. The Zn(II) isoleucine dithiocarbamate complex may have promising potential as an anticancer compound due to its significant inhibitory effect on the breast cancer cell line (MCF7). According to the ADMET study, the complex exhibits drug-like characteristics with low toxicity, further supporting its potential as a viable drug candidate.