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AIM: The primary objective of this study was to elucidate the putative cell wall-associated targets of compound 6i, a glycoconjugate of eugenol, in Aspergillus fumigatus, while also evaluating its toxicity and assessing histopathologic alterations in the liver, heart, and kidney of compound 6i-treated embryos using an in ovo model. METHOD: To achieve this aim, compound 6i was synthesized, and a series of biochemical assays were performed to determine its impact on the fungal cell wall. Additionally, qRT-PCR and LC-MS/MS analyses were conducted to investigate changes in gene and protein expression profiles associated with melanin biosynthesis, conidiation, siderophore production, transcriptional regulation of ß-glucan biosynthesis, and calcineurin activity in A. fumigatus. RESULTS: The experimental findings revealed that compound 6i exhibited notable antifungal activity against A. fumigatus by perturbing cell wall integrity, hindering ergosterol, glucan, and chitin biosynthesis, and inhibiting catalase production. Moreover, relative gene expression and proteomic analyses demonstrated that compound 6i exerted both down-regulatory and up-regulatory effects on several crucial genes and proteins involved in the aforementioned fungal processes. Furthermore, increased expression of oxidative stress-related proteins was observed in the presence of compound 6i. Notably, the glycoconjugate of eugenol did not elicit cytotoxicity in the liver, heart, and kidney of chick embryos. CONCLUSION: The current investigation elucidated the multifaceted mechanisms by which compound 6i exerts its antifungal effects against A. fumigatus, primarily through targeting cell wall components and signaling pathways. These findings underscore the potential of the eugenol glycoconjugate as a promising antifungal candidate, warranting further exploration and development for combating A. fumigatus infections.
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BACKGROUND: Group B Streptococcus (GBS) is a causative agent of various infections in newborns, immunocompromised (especially diabetic) non-pregnant adults, and pregnant women. Antibiotic resistance profiling can provide insights into the use of antibiotic prophylaxis against potential GBS infections. Virulence factors are responsible for host-bacteria interactions, pathogenesis, and biofilm development strategies. The aim of this study was to determine the biofilm formation capacity, presence of virulence genes, and antibiotic susceptibility patterns of clinical GBS isolates. RESULTS: The resistance rate was highest for penicillin (27%; n = 8 strains) among all the tested antibiotics, which indicates the emergence of penicillin resistance among GBS strains. The susceptibility rate was highest for ofloxacin (93%; n = 28), followed by azithromycin (90%; n = 27). Most GBS strains (70%; n = 21) were strong biofilm producers and the rest (30%; n = 9) were moderate biofilm producers. The most common virulence genes were cylE (97%), pavA (97%), cfb (93%), and lmb (90%). There was a negative association between having a strong biofilm formation phenotype and penicillin susceptibility, according to Spearman's rank correlation analysis. CONCLUSION: About a third of GBS strains exhibited penicillin resistance and there was a negative association between having a strong biofilm formation phenotype and penicillin susceptibility. Further, both the strong and moderate biofilm producers carried most of the virulence genes tested for, and the strong biofilm formation phenotype was not associated with the presence of any virulence genes.
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Infecções Estreptocócicas , Streptococcus agalactiae , Feminino , Gravidez , Humanos , Sorogrupo , Virulência/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos , Infecções Estreptocócicas/microbiologia , Penicilinas/farmacologia , Biofilmes , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade MicrobianaRESUMO
Copper-catalyzed [3 + 2] cycloadditions of N-tosylcyclopropylamine with alkynes and alkenes have been accomplished under visible light irradiation. The developed approach is compatible with a range of functionalities and allows the synthesis of diversified aminated cyclopentene and cyclopentane derivatives being relevant for drug synthesis. The protocol is operationally simple and economically affordable as it does not require any ligand, base, or additives. As the key step, the one-electron oxidation of the N-tosyl moiety by visible light-induced homolysis of a transient Cu(II)-tosylamide complex is proposed, providing a facile entry for N-centered radicals.
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Alcenos , Alcinos , Catálise , Cobre , Reação de Cicloadição , LuzRESUMO
DNA strands consisting of multiple runs of guanines can adopt a noncanonical, four-stranded DNA secondary structure known as G-quadruplex or G4 DNA. G4 DNA is thought to play an important role in transcriptional and translational regulation of genes, DNA replication, genome stability, and oncogene expression in eukaryotic genomes. In other organisms, including several bacterial pathogens and some plant species, the biological roles of G4 DNA and G4 RNA are starting to be explored. Recent investigations showed that G4 DNA and G4 RNA are generally conserved across plant species. In silico analyses of several bacterial genomes identified putative guanine-rich, G4 DNA-forming sequences in promoter regions. The sequences were particularly abundant in certain gene classes, suggesting that these highly diverse structures can be employed to regulate the expression of genes involved in secondary metabolite synthesis and signal transduction. Furthermore, in the pathogen Mycobacterium tuberculosis, the distribution of G4 motifs and their potential role in the regulation of gene transcription advocate for the use of G4 ligands to develop novel antitubercular therapies. In this review, we discuss the various roles of G4 structures in bacterial DNA and the application of G4 DNA as inhibitors or therapeutic agents to address bacterial pathogens.
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Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Quadruplex G , Animais , DNA Bacteriano , Regulação Bacteriana da Expressão Gênica , Genoma Bacteriano , Instabilidade Genômica , Guanina , Humanos , Ligantes , VirulênciaRESUMO
PURPOSE: The study aimed to evaluate the effect of sensorimotor training on spatiotemporal parameters of gait among middle-aged and older adults with diabetic peripheral neuropathy (DPN). METHODS: A randomised controlled study with four parallel arms (two intervention groups and two control groups) was conducted. Thirty-seven DPN patients were selected on the basis of inclusion and exclusion criteria. Of these, 16 middle-aged and 21 older adults were randomly allocated to the intervention and control groups. Participants in the intervention group were administered eight weeks (three days/week) of sensorimotor training along with diabetes and foot care education whereas participants in the control group received only diabetes and foot care education. Outcome measures involved spatiotemporal parameters of gait at self-paced and maximal-paced, measured before and after eight weeks. RESULTS: Age difference was found to be significant in velocity (p ≤ 0.013) and stride length (p ≤ 0.017) at self-paced and maximal-paced walking. After the intervention, velocity was found to be a significant group effect and time × group interaction at self-paced (p = 0.003) and maximal-paced (p = 0.003) walking. Stride length (p = 0.006) was found to be a significant group effect and time × group interaction at self-paced only. Cadence (p = 0.041) and gait cycle (p = 0.05) were found to be significant time × group interaction only at maximal-paced walking. Stance (p ≤ 0.047) and double limb support (p ≤ 0.02) were found to be significant group effect and time × group interaction at self-paced and maximal-paced walking. CONCLUSION: Sensorimotor training improves spatiotemporal parameters of gait after eight weeks in similar fashion in middle-aged and older age DPN patients, regardless of age.
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Diabetes Mellitus , Neuropatias Diabéticas , Idoso , Marcha , Humanos , Pessoa de Meia-Idade , CaminhadaRESUMO
BACKGROUND: Peritoneal dialysis (PD) as a modality of kidney replacement therapy (KRT) is largely underutilized globally. We analyzed PD utilization, impact of economic status, projected growth and impact of state policy(s) on PD growth in South Asia and Southeast Asia (SA&SEA) region. METHODS: The National Nephrology Societies of the region responded to a questionnaire on KRT practices. The responses were based on the latest registry data, acceptable community-based studies and societal perceptions. The representative countries were divided into high income and higher-middle income (HI & HMI) and low income and lower-middle income (LI & LMI) groups. RESULTS: Data provided by 15 countries showed almost similar percentage of GDP as health expenditure (4%-7%). But there was a significant difference in per capita income (HI & HMI -US$ 28 129 vs. LI & LMI - US$ 1710.2) between the groups. Even after having no significant difference in monthly cost of haemodialysis (HD) and PD in LI & LMI countries, they have poorer PD utilization as compared to HI & HMI countries (3.4% vs. 10.1%); the reason being lack of formal training/incentives and time constraints for the nephrologist while lack of reimbursement and poor general awareness of modalities has been a snag for the patients. The region expects ≥10% PD growth in the near future. Hong Kong and Thailand with 'PD first' policy have the highest PD utilization. CONCLUSION: Important deterrents to PD underutilization were lack of PD centric policies, lackadaisical patient/physician's attitude, lack of structured patient awareness programs, formal training programs and affordability.
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Países em Desenvolvimento , Gastos em Saúde/tendências , Política de Saúde/tendências , Nefropatias/terapia , Nefrologistas/tendências , Nefrologia/tendências , Diálise Peritoneal/tendências , Padrões de Prática Médica/tendências , Ásia/epidemiologia , Atitude do Pessoal de Saúde , Países em Desenvolvimento/economia , Previsões , Produto Interno Bruto , Pesquisas sobre Atenção à Saúde , Gastos em Saúde/legislação & jurisprudência , Conhecimentos, Atitudes e Prática em Saúde , Política de Saúde/economia , Política de Saúde/legislação & jurisprudência , Humanos , Renda , Nefropatias/economia , Nefropatias/epidemiologia , Nefrologistas/economia , Nefrologistas/legislação & jurisprudência , Nefrologia/economia , Nefrologia/legislação & jurisprudência , Diálise Peritoneal/economia , Formulação de Políticas , Padrões de Prática Médica/economia , Padrões de Prática Médica/legislação & jurisprudênciaRESUMO
AIM: There is paucity of data on the epidemiology of end-stage kidney disease (ESKD) from South Asia and South-East Asia. The objective of this study was to assess the aetiology, practice patterns and disease burden and growth of ESKD in the region comparing the economies. METHODS: The national nephrology societies of the region; responded to the questionnaire; based on latest registries, acceptable community-based studies and society perceptions. The countries in the region were classified into Group 1 (High|higher-middle-income) and Group 2 (lower|lowermiddle income). Student t-test, Mann-Whitney U test and Fisher's exact test were used for comparison. RESULTS: Fifteen countries provided the data. The average incidence of ESKD was estimated at 226.7 per million population (pmp), (Group 1 vs. Group 2, 305.8 vs. 167.8 pmp) and average prevalence at 940.8 pmp (Group 1 vs. Group 2, 1306 vs. 321 pmp). Group 1 countries had a higher incidence and prevalence of ESKD. Diabetes, hypertension and chronic glomerulonephritis were most common causes. The mean age in Group 2 was lower by a decade (Group 1 vs. Group 2-59.45 vs 47.7 years). CONCLUSION: Haemodialysis was the most common kidney replacement therapy in both groups and conservative management of ESKD was the second commonest available treatment option within Group 2. The disease burden was expected to grow >20% in 50% of Group 1 countries and 78% of Group 2 countries along with the parallel growth in haemodialysis and peritoneal dialysis.
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Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Padrões de Prática Médica/tendências , Diálise Renal/tendências , Adulto , Distribuição por Idade , Idoso , Ásia/epidemiologia , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Incidência , Falência Renal Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/tendências , Prevalência , Medição de Risco , Fatores de RiscoRESUMO
A psychrotolerant Sphingobacterium sp. was isolated from the apple orchard situated in the Kufri region of Shimla, Himachal Pradesh, India using an enrichment culture technique having chlorpyrifos (CP) as the sole source of carbon and energy. Based on biochemical characterization and 16S rRNA analysis, the strain was identified as Sphingobacterium sp. C1B. The bacterium C1B was able to degrade chlorpyrifos ≥ 42 ppm and ≥ 36 ppm within 14 days at 20 °C and 15 °C, respectively. The strain was also able to degrade chlorpyrifos ≤ 35 ppm at 28 °C within 14 days. The enzyme organophosphorus hydrolase might be responsible for the initial degradation of CP by the strain C1B. Based on the HPLC and GCMS analysis, a probable degradation pathway has been proposed, which followed the path from chlorpyrifos to 3,5,6-trichloro-2-pyridinol to benzene, 1,3-bis (1,1-dimethylethyl) and then entered into the TCA cycle. Our current study revealed that the bacterium C1B was found to be a useful strain for the degradation of pesticide chlorpyrifos in the cold climatic environment.
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Biodegradação Ambiental , Clorpirifos/metabolismo , Malus/microbiologia , Praguicidas/metabolismo , Sphingobacterium/metabolismo , Temperatura Baixa , Índia , RNA Ribossômico 16S , Sphingobacterium/genéticaRESUMO
OBJECTIVES: To examine the effect of sensorimotor and gait training on proprioception, nerve function, and muscle activation in diabetic peripheral neuropathy (DPN) patients. METHODS: Thirty-eight (25 male and 13 female) participants with DPN were selected and randomly allocated to intervention and control group. Participants in the intervention group were provided sensorimotor and gait training for eight weeks (3 days/week) along with diabetes and foot care education; participants in the control group received diabetes and foot care education only. Outcome measures involved proprioception, nerve conduction studies of peroneal and tibial nerve, and activation of lower limb muscles and multifidus while standing with eyes open and eyes closed, and treadmill walking. RESULTS: Mixed ANOVA revealed significant time effect and time×group interaction of proprioception in all four directions (p<0.05). The conduction velocity of peroneal nerve revealed significant time effect (p=0.007) and time×group interaction (p=0.022). Interaction effect was found to be significant for medial gastrocnemius and multifidus while standing with eyes open as well as with eyes closed (p≤0.004). Only multifidus showed significant group (p=0.002) and interaction effect (p=0.003) during walking. CONCLUSIONS: Sensorimotor and gait training is an effective tool for improvement of proprioception and nerve function. It benefits muscle activation around ankle and multifidus during postural control and walking in DPN patients. Clinical Trials Registry - India, National Institute of Medical Statistics (Indian Council of Medical Research): Registration Number - CTRI/2017/08/009328.
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Neuropatias Diabéticas/reabilitação , Terapia por Exercício/métodos , Equilíbrio Postural/fisiologia , Propriocepção/fisiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Copper-mediated direct ortho-C-H amination of arenes has been accomplished with the aid of easily removable bidentate pyridine N-oxide as a directing group. The use of free cyclic secondary amines and anilines as aminating agents and inexpensive copper acetate makes the strategy more effective and favorable from the economic point of view. This reaction is compatible with a wide range of functional groups to synthesize a variety of amine-containing products of high interest. This method also allows the short synthesis of the central scaffold of pharmaceutically relevant Staphylococcus aureus Sortase A inhibitors.
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Aminas/química , Cobre/química , Hidrocarbonetos Aromáticos/química , Aminação , CatáliseRESUMO
An efficient approach for the synthesis of functionalized tetrahydro-pyrido/quinolinocarbazoles from 2-alkynylindole-3-carbaldehydes and l-proline utilizing a metal-free decarboxylative cyclization, ring expansion, and ring contraction strategy via the generation of azomethine ylide was developed. The reaction of 2-alkynylindole-3-carbaldehydes with l-thioproline leads to the formation of γ-carbolines. By virtue of this expedient method, a diverse range of biologically active heteroannulated carbazoles can be synthesized efficiently.
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BACKGROUND: Mobile health (mHealth) is emerging as the most convenient way to deliver rehabilitation services remotely, and collect outcomes in real time, thus contributing to disease management by transferring care from hospital to home. It facilitates accessibility to healthcare, enhances patients' understanding of their condition, and their willingness to engage in self-management, giving way to high-quality care to the satisfaction of both patients and healthcare professionals. PURPOSE: The purpose of this study was to examine the effect of using a smartphone app (called Snapcare) on pain and function in patients suffering from chronic low back pain. METHODS: Ninety-three patients with chronic low back pain were recruited and randomly allocated to either the Conventional group (n = 48) receiving a written prescription from the Physician, containing a list of prescribed medicines and dosages, and stating the recommended level of physical activity (including home exercises) or the App group (n = 45) receiving Snapcare, in addition to the written prescription. Pain and disability were assessed at baseline and after 12 weeks of treatment. RESULTS: Both the groups showed significant improvement in pain and disability (p < 0.05). The App group showed a significantly greater decline in disability (p < 0.001). CONCLUSION: Health applications are promising tools for improving outcomes in patients suffering from various chronic conditions. Snapcare facilitated increase in physical activity and brought about clinically meaningful improvements in pain and disability in patients with chronic low back pain. These slides can be retrieved under Electronic Supplementary Material.
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Dor Crônica/terapia , Dor Lombar/terapia , Aplicativos Móveis , Autocuidado , Smartphone , Humanos , Autocuidado/instrumentação , Autocuidado/métodos , TelemedicinaRESUMO
Pesticides play an important role in the protection of different crops. Among the diverse sets of pesticides used all over the world, the organophosphates are the most widely used group. Profenofos [O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate] is one of the most largely used organophosphate insecticides on field crops, vegetables, and fruit crops. The World Health Organization classifies this compound as moderately hazardous (Toxicity Class II), and its residues have been found in vegetables like okra [ (L.) Moench], gooseberries ( sp.), green chilies [ (L.)], curry leaves [ (L.) Spreng], mint leaves [ (L.)], and coriander leaves [ (L.)]. Dietary intake of profenofos (PFF) is the major exposure pathway for humans. When applied to agricultural fields, PFF residues spread into every part of the environment: ambient air, surface water, and soil. In this review, we discuss the worldwide usage of PFF pesticide, its toxic effects on humans and other living organisms in the environment, and biodegradation of this chemical by various microbial strains. To date, no complete biodegradation pathway has been established for PFF pesticide, calling for a study of this nature.
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Biodegradação Ambiental , Organotiofosfatos/toxicidade , Praguicidas/toxicidade , Acetilcolinesterase , Humanos , Organotiofosfatos/metabolismo , Praguicidas/metabolismoRESUMO
Monocytes are critical components of the innate immune system and they can differentiate into dendritic cells (DCs). Cutaneous neoplasms of dendritic cell origin are uncommon and mostly represented by histiocytic lesions derived primarily from Langerhans cells. The myeloid DC (mDC) while recognized in the immunology literature does not have a well-defined neoplastic cutaneous counterpart. Eleven patients with a diagnosis of cutaneous mDC dyscrasia were evaluated. Routine hematoxylin and eosin stain were performed followed by selective phenotypic studies. The patients were older without a gender predilection and exhibited an asymptomatic papular skin rash with a waxing and waning course. The biopsies demonstrated a dermal based monomorphic small mononuclear cell infiltrate. The cells expressed CD14, CD11c, HLA-DR, as well as granzyme and lysozyme that defines terminally differentiated monocyte/dendritic cells. Expression of BDCA-3 (CD141) by the tumor cells indicated that they were myeloid dendritic cells (mDC2). Each patient had a prior or subsequent diagnosis of an abnormal bone marrow biopsy that included myelodysplastic syndrome, myelofibrosis, chronic myelomonocytic leukemia, and acute myelogenous leukemia. We propose the term cutaneous mDC cell dyscrasia for distinctive infiltrates of differentiated mDCs reflective of underlying myeloproliferative disease. The clinical course is variable and can be indolent although it is strongly correlated with myelodysplastic syndrome that included leukemia.
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Medula Óssea/patologia , Células Dendríticas/citologia , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/patologia , Monócitos/patologia , Transtornos Mieloproliferativos/patologia , Dermatopatias/patologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Células de Langerhans/patologia , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/etiologia , Dermatopatias/etiologiaRESUMO
[Purpose] The present study aimed to determine the changes in physical and balance performance following exercise-induced muscle damage using a sport-specific protocol. [Subjects and Methods] Fifteen collegiate soccer players were asked to perform a sport-specific sprint protocol to induce muscle damage. The markers of muscle damage (soreness, range of motion, limb girth, muscle strength, creatine kinase and lactate dehydrogenase), physical performance (speed, agility and power) and balance (static and dynamic balance) were assessed at baseline and 24, 48 and 72 hours following the sprint protocol. [Results] All variables, including the markers of muscle damage, physical performance and balance showed a significant difference when assessed at the 4 time points. [Conclusion] The study demonstrated that both the physical and balance performance were affected following repeated sprint protocol in soccer players. It is recommended the balance performance of an athlete be continually assessed following exercise-induced muscle damage so as to determine the appropriate return to sport decision thereby, minimizing the risk of further injury.
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INTRODUCTION: The COVID-19 pandemic affected the healthcare system worldwide. Cancer patients and oncologists faced challenges equally in the context of the pandemic. The present study was undertaken to assess the impact of COVID-19 on cancer patients, encompassing infection source, care type, treatment delays, and infection outcomes. MATERIALS AND METHOD: This single-center retrospective study was conducted between March 2020 and January 2022 at North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, India. It examined COVID-19 cases in cancer patients with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription-polymerase chain reaction (RT-PCR) results. Data collection included demographics, clinical details, COVID-19 specifics, treatment delays, and infection outcomes. RESULT: In our study of 9,854 oncology patients' visits, 26 (0.26%) tested COVID-19 positive by RT-PCR, aged three to 70 years with a male-female ratio of 1:1.67. Twenty-three percent had comorbidities, mainly hypertension. Gastrointestinal cancers (30.8%) and hepatobiliary origin (15.5%) were common. Most patients (69.2%) had stage IV cancer, and 34.6% aimed for curative treatment. The majority of the patients (76.9%) were community-acquired, and the rest (23.1%) contracted during hospital stay. Fever (34.5%) and asymptomatic infection (30.8%) were common presentations. Six (23.1%) comorbid patients required ICU care. Median treatment delay was three weeks, with one COVID-19-related death (3.8%) and six cancer-related deaths. On follow-up, 19.2% had stable disease, 7.7% partial response, 7.7% recurrence, and 23.1% had progression. CONCLUSION: Amid the pandemic, cancer patients safely received treatment. Mild cases were managed at home. Poor outcome was found in comorbid, severe COVID-19 cancer patients. However, the impact of treatment delays on long-term oncological outcomes needs further study.
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Acyl-Coenzyme A binding domain containing proteins (ACBDs) are ubiquitous in nearly all eukaryotes. They can exist as a free protein, or a domain of a large, multidomain, multifunctional protein. Besides modularity, ACBDs also display multiplicity. The same organism may have multiple ACBDs, differing in sequence and organization. By virtue of this diversity, ACBDs perform functions ranging from transport, synthesis, trafficking, signal transduction, transcription, and gene regulation. In plants and some microorganisms, these ACBDs are designated ACBPs (acyl-CoA binding proteins). The simplest ACBD/ACBP is a small, â¼10 kDa, soluble protein, comprising the acyl-CoA binding (ACB) domain. Most of these small ACBDs exist as monomers, while a few show a tendency to oligomerize. In sync with those studies, we report the crystal structure of two ACBDs from Leishmania major, named ACBP103, and ACBP96 based on the number of residues present. Interestingly, ACBP103 crystallized as a monomer and a dimer under different crystallization conditions. Careful examination of the dimer disclosed an exposed 'AXXA' motif in the helix I of the two ACBP103 monomers, aligned in a head-to-tail arrangement in the dimer. Glutaraldehyde cross-linking studies confirm that apo-ACBP103 can self-associate in solution. Isothermal titration calorimetry studies further show that ACBP103 can bind ligands ranging from C8 - to C20-CoA, and the data could be best fit to a 'two sets of sites'/sequential binding site model. Taken together, our studies show that Leishmania major ACBP103 can self-associate in the apo-form through a unique dimerization motif, an interaction that may play an important role in its function.
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Motivos de Aminoácidos , Leishmania major , Multimerização Proteica , Leishmania major/metabolismo , Leishmania major/genética , Acil Coenzima A/metabolismo , Acil Coenzima A/química , Cristalografia por Raios X , Ligação Proteica , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Sequência de Aminoácidos , Modelos Moleculares , Sítios de LigaçãoRESUMO
CONTEXT AND OBJECTIVE: Tobacco smoke and nitrostable foods containing N-methyl N-nitrosourea (MNU) are among the primary causes of liver cancer. To substantiate the beneficial claims ascribed to Aegle marmelos (L.) Corrêa (Rutaceae), the hepatoprotective potential of its leaf extract was studied using an MNU-induced hepatocarcinogenesis model in Balb/c mice. MATERIALS AND METHODS: After dose selection, 40 mice were randomly assigned to 4 groups: I (control), II (intraperitoneally (i.p.) primed with 50 mg/kg MNU), III (100 mg/kg A. marmelos hydroalcoholic extract (HEAM) i.p.) and IV (MNU + HEAM, i.p.). Inflammatory (IL-1ß, IL-6), anti-inflammatory (IL-4) cytokine expression, apoptosis (Bcl-2) and tumor-related (p53, c-jun) genes were assessed at mRNA level. HEAM effects on hematological parameters were examined. RESULTS AND DISCUSSION: HEAM treatment decreased IL-1ß, IL-6, Bcl-2 and c-jun respectively expressions by 90, 25, 53 and 30%, respectively. p53 and IL-4 expression was up-regulated by 1.5- and 2-fold. MNU decreased hemoglobin concentration (25%), lymphocyte count (42%) and increased leukocyte (100%), platelet (4-fold), neutrophil (43%), monocyte (10-fold) and eosinophil (10-fold) counts in Group II mice while HEAM modulated the same parameters by -7%, -21%, +24%, +3-fold, +12%, +3-fold and +4-fold, respectively, in MNU-induced mice compared to control. HEAM protective effect was confirmed by Raman spectroscopy where the MNU-induced peak at 1252 cm(-1) was normalized. DNA fragmentation data suggest apoptosis as one of the protective mechanisms of HEAM. CONCLUSION: The hepatoprotective, anti-carcinogenic and immunomodulatory effects of A. marmelos extract indicate potential beneficial effects in cancer therapy.
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Anticarcinógenos/farmacologia , Fatores Imunológicos/farmacologia , Neoplasias Hepáticas Experimentais/prevenção & controle , Metilnitrosoureia , Extratos Vegetais/farmacologia , Aegle/química , Animais , Anticarcinógenos/administração & dosagem , Anticarcinógenos/isolamento & purificação , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/isolamento & purificação , Mediadores da Inflamação/metabolismo , Injeções Intraperitoneais , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Plantas Medicinais , Fatores de TempoRESUMO
Among the organophosphate pesticides, the wide and indiscriminate use of profenofos (PFF) in agricultural and horticultural crops has resulted in serious environmental and animal health concerns and therefore demands an urgent need to develop a biological solution for its effective removal from the environment. For the bioremediation of PFF, a strain PF1, capable of utilizing profenofos as the sole source of carbon and energy was isolated from the soil samples of apple orchards of Shimla region of Himachal Pradesh, India. Based on the biochemical, FAME, and 16S rRNA gene analysis the bacterium PF1 was identified as Bacillus altitudinis (GenBank: MH986176). The strain was able to degrade 50µg mL-1 PFF up to 93% within 30 days of incubation at 28°C, pH 7.0. A linear regression analysis performed on the data-set revealed the statistical significance of the relationship between the growth of the bacterial population and the degradation of pesticides. The compound 4-Bromo-2-chlorophenol (BCP) was detected as one of the pathway metabolites which further were completely degraded to lower pathway metabolites. A probable PFF degradation pathway has been proposed which follows the path from PFF to BCP and ultimately enters into the TCA cycle. To the best of our knowledge, this is the first report of PFF biodegradation by any Bacillus species of western Himalayan origin exhibiting close phylogenetic association with Bacillus altitudinis. This indigenous bacterium can be useful to bio-remediate the PFF contaminated soil as this pesticide is extensively used in the different horticulture fields in Himachal Pradesh, India.
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Bacillus , Clorofenóis , Praguicidas , Animais , Praguicidas/metabolismo , Compostos Organofosforados , Biodegradação Ambiental , RNA Ribossômico 16S/genética , Filogenia , Bacillus/genética , Bacillus/metabolismo , Solo , Microbiologia do SoloRESUMO
A base-mediated versatile cascade dual-annulation and formylation of 2-alkenyl/alkynylbenzonitriles with 2-methylbenzonitriles has been established for the construction of four different classes of amino and amido substituted benzo[c]phenanthridines and benzo[c]phenanthrolines. The synthesized molecules could be of utmost relevance in pharmaceuticals. The transformation uses the solvent DMF as the formyl source for synthesis of the amido-substituted scaffolds. This transition-metal-free unique strategy enables the formation of multiple C-C and C-N bonds in one pot at room temperature.