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1.
Minerva Med ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33949182

RESUMO

Retinal vein occlusion is an important cause of vision loss. The current treatment options are mainly directed to the prevention of neovascular complications and few studies have addressed to potential use of anticoagulant agents and other interventions targeting the coagulation system. Herein we review the general aspects of this condition focusing on the potential benefits of anticoagulant treatment.

2.
J Med Case Rep ; 15(1): 262, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33947445

RESUMO

BACKGROUND: Low-grade endometrial stromal sarcoma is a rare neoplastic growth in the uterine cavity, representing less than 1% of uterine tumors. Such tumors usually affect premenopausal and perimenopausal women, with a mean age of 46 years. Treatment generally starts with surgical resection of the tumor, followed by chemotherapy, radiotherapy, or hormonal therapy. CASE PRESENTATION: In the current report, we again present a case of low-grade endometrial stromal sarcoma in a 51-year-old Mediterranean woman presenting with abdominopelvic pain. Computed tomography scan revealed a primary uterine tumor measuring 17 × 9 × 9 cm metastasizing to the lungs, bladder, and ureteral orifice, along with lymphovascular involvement. The patient underwent total abdominal hysterectomy, omentectomy, and lymph node dissection. Estrogen deprivation was accomplished by bilateral salpingo-oophorectomy. Lifelong hormonal therapy consisting of letrozole 2.5 mg per day was prescribed, which demonstrated remarkable efficacy, resulting in a partial remission of lung metastasis within 8 months after surgery. Full remission was observed after 18 months of hormonal therapy, with no recurrence. Another scan was performed after 2.5 years, revealing complete remission with no recurrence. CONCLUSION: We again report a case of complete remission of low-grade endometrial stromal sarcoma after surgical removal of the tumor along with first-line hormonal therapy without the use of chemotherapy or radiotherapy, emphasizing the role of hormonal therapy in the treatment of such tumors.

3.
J Colloid Interface Sci ; 599: 227-244, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33945970

RESUMO

The current study provides a novel insight into the role of synergism of the changes in Mg2+/ Al3+ in the best catalytic activity of indol-3-yl derivatives. A series of Co-Mg-Al layered triple hydroxides (LTHs) catalysts were produced by altering the Al3+/Mg2+ ratio with respect to Co2+. The physicochemical properties of LTHs were well characterized by ICP-AES, XRD, FTIR, FE-SEM, BET, Zeta-sizer, and VSM. The results show that the sample CMA4 (Co2+:Mg2+:Al3+ 2:4:4) is an exception to the physicochemical characteristics of the produced Co-Mg-Al LTHs, which is due to the synergism between the changes in Mg2+ and Al3+. To the best of our knowledge, this is the first study to report the synthesis of indol-3-yl derivatives from indole-3-carbaldehyde using Co-Mg-Al LTHs as highly efficient heterogeneous catalysts, which is an extremely appealing path. The selectivity of the synthesis was studied by condensing various nucleophiles through the one-pot method that established superior reactivity under mild conditions. Notably, the results show that the Co-Mg-Al LTHs system exhibited an extraordinarily catalytic activity, with the highest yield (98%) being obtained under the following optimal conditions: the concentration of Co-Mg-Al LTHs = 5 mol%, 30 min., water/ethanol as solvent. Furthermore, the reusable studies exhibited that the catalysts were found to be stable and reusable for up to six cycles without substantial loss of catalytic activity. Finally, a plausible reaction mechanism of the Co-Mg-Al LTHs system for indol-3-yl derivatives was put forward according to our comprehensive analysis. Our work illuminates a cheap and flexible strategy for the synthesis of indol-3-yl derivatives using Co-Mg-Al LTHs.

4.
Cancers (Basel) ; 13(6)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809455

RESUMO

Bacillus Calmette-Guérin (BCG) is commonly used in the immunotherapy of bladder cancer (BlCa) but its effectiveness is limited to only a fraction of patients. To identify the factors that regulate the response of human BlCa tumor microenvironment (TME) to BCG, we used the ex vivo whole-tissue explant model. The levels of COX2 in the BCG-activated explants closely correlated with the local production of Treg- and MDSCS attractants and suppressive factors, while the baseline COX2 levels did not have predictive value. Accordingly, we observed that BCG induced high levels of MDSC- and Treg-attracting chemokines (CCL22, CXCL8, CXCL12) and suppressive factors (IDO1, IL-10, NOS2). These undesirable effects were associated with the nuclear translocation of phosphorylated NFκB, induction of COX2, the key enzyme controlling PGE2 synthesis, and elevation of a PGE2 receptor, EP4. While NFκB blockade suppressed both the desirable and undesirable components of BCG-driven inflammation, the inhibitors of PGE2 synthesis (Celecoxib or Indomethacin) or signaling (EP4-selective blocker, ARY-007), selectively eliminated the induction of MDSC/Treg attractants and immunosuppressive factors but enhanced the production of CTL attractants, CCL5, CXCL9 and CXCL10. PGE2 blockade allowed for the selectively enhanced migration of CTLs to the BCG-treated BlCa samples and eliminated the enhanced migration of Tregs. Since the balance between the CTLs and suppressive cells in the TME predicts the outcomes in patients with BlCa and other diseases, our data help to elucidate the mechanisms which limit the effectiveness of BCG therapies and identify new targets to enhance their therapeutic effects.

5.
Nurse Educ Pract ; 52: 103041, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33866236

RESUMO

Assessing knowledge, attitude, and practices of healthcare students regarding any infectious outbreak became a fundamental step to set an effective plan related to their preparedness. The purpose of this study was to assess COVID-19 knowledge, attitude, and precautionary practices among health professional students in Oman. Data were collected using the Web-based survey method. The sample was recruited from the largest college of Medicine in Oman, while the nursing sample was recruited from two different nursing colleges in Oman. The study tool was developed based on the most recent advisory COVID-19 recommendations from the WHO and the CDC. A total of 222 students filled the survey, of which 55% were medical students and 59.9% were females. The mean knowledge score was 16.5 (SD = 4.2), which represents 66% of the highest possible score, with 25.7% were classified as 'excellent knowledge'. Participants reported a high level of public precautionary practices (M = 44.1, SD = 5.0), which represents 84.6% of the highest score, with 61.3% were classified as 'high compliance. The mean attitude score was 40.3 (SD = 5.9), which represents 67% of the highest possible score. According to the classification categories, most students (81%, n = 180) expressed a positive attitude toward COVID-19. More efforts should be done toward preparing the healthcare students to deal with the outbreak. Preparing healthcare students with the right knowledge, attitude, and precautionary practices during the COVID-19 outbreak is very essential to patient and public safety. Healthcare students can play a major role in increasing public awareness about COVID-19 precautionary practices.

6.
Libyan J Med ; 16(1): 1918903, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33899704

RESUMO

Dehydration is linked to worse cognitive functions and preference for beverages that are linked to obesity and other health conditions. Saudi Arabia's hot climate can exacerbate these effects and it is important to ensure that children in the region understand the benefits of adequate water intake. To evaluate secondary school student perceptions and practices regarding water intake, investigate how water intake is related to BMI and school performance, and compare international schools to national schools. This cross-sectional study surveyed understanding and practices relating to water intake of national and international secondary school students using a questionnaire based on a random selection of schools and students. One-hundred and sixty-two students from international schools (I) and 157 from national schools (N) responded. Most were aged 16 and 17 years old (I:61.1%, N:76.5%, p = .005). The average BMI of all students was 24.9 ± 6.013 (I:23.6 ± 4.658, N:26.1 ± 6.931, p < 0.001). Students understood beverages do not replace water intake (I:80.2%, N:75.8%, p = .337) and preferred water when thirsty (I:77.8%, N:75.2%, p = .549). However, water consumption was low with more than 50% of students drinking less than 1500 ml a day (I:54.3%, N:70.7%, p = .002). A positive correlation between BMI and water intake was observed only among international school students. Students have inadequate water intake despite understanding the importance of hydration. There are some differences between international school students and national school students that can be attributed to the availability and sources of water, though other factors cannot be excluded.

7.
8.
Nat Prod Res ; : 1-6, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33886378

RESUMO

30 secondary polyphenolic metabolites were characterised in Eucalyptus kino methanol extract using HPLC-MS/MS. The antitumor activity of the extract in combination with low level ionising radiation in female mice with solid tumors from inoculated Ehrlich ascites carcinoma cells was investigated. Tumor cell-inoculated mice received daily extract doses (100 mg/kg, 200 mg/kgBW) with or without a single exposure to 0.25 Gy γ-rays, and cis-platin as a reference anticancer drug. Changes in the tumor volume, oxidative state, levels of caspase-3, TGF-ß and Nf-κB were assessed by q-PCR. Surprisingly, a dose of 200 mg/kg extract together with γ-radiation remarkably reduced the tumor volume, improved the oxidative and apoptotic biomarker levels. In conclusion, results showed that a combination of kino extract with low level γ-radiation synergistically reduced tumor progression due to the antioxidant and anti-proliferative activities of the polyphenolics in the extract.

9.
Acta Parasitol ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33886040

RESUMO

BACKGROUND: Neoechinorhynchus cylindratus Van Cleave (Zoo Anz 43: 177-1990, 1913) Van Cleave (Ill Natl Hist Surv Bull 13:225-257, 1919) is a North American acanthocephalan originally described from Micropterus salmoides (Lacépède) in Pelican Lake, Minnesota. It is common in Centrarchids but also not infrequent in fishes of other families. PURPOSE: A unique population of N. cylindratus was discovered in Peru. It needed to be described and its introduction into Peru investigated. METHODS: Standard processing of specimens and staining in Borax carmine and fast green for creating whole mounts were employed. Literature sources were available from the OMA personal collection. RESULTS: The descriptive accounts of N. cylindratus have been rather stable over the years since its original description. It has been, however, oddly identified from Gambusia affinis (Baird and Girard) in Peru. Females of the Peruvian specimens were, however, not typical in having a terminal-near terminal gonopore at odds with the sub-ventral position characteristic of the usual populations of N. cylindratus in North America. We describe the Peruvian material and outline the distinct morphological variations from the North American populations in the position of the female gonopore, among other characters. We also explain its introduction into Peru and the translocation of the position of female gonopore to the terminal position. CONCLUSIONS: The translocation to the terminal position of the female gonopore in the Peruvian material is attributed to host related developmental factors. The route of introduction of N. cylindratus into Peru through the introduction of G. affinis from the United States has been accounted for. It may be comparable to the introduction of the same acanthocephalan species into northern Mexico via the documented introduction of its primary host, M. salmoides, also from the United States into Mexico in 1930. The introduction of Acanthocephalus dirus Van Cleave (Ill Natl Hist Surv Bull 13:225-257, 1919) (Van Cleave and Townsend, 1936) into Mexico is also discussed.

10.
Nat Commun ; 12(1): 2043, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824312

RESUMO

The tumour suppressor FBW7 is a substrate adaptor for the E3 ubiquitin ligase complex SKP1-CUL1-F-box (SCF), that targets several oncoproteins for proteasomal degradation. FBW7 is widely mutated and FBW7 protein levels are commonly downregulated in cancer. Here, using an shRNA library screen, we identify the HECT-domain E3 ubiquitin ligase TRIP12 as a negative regulator of FBW7 stability. We find that SCFFBW7-mediated ubiquitylation of FBW7 occurs preferentially on K404 and K412, but is not sufficient for its proteasomal degradation, and in addition requires TRIP12-mediated branched K11-linked ubiquitylation. TRIP12 inactivation causes FBW7 protein accumulation and increased proteasomal degradation of the SCFFBW7 substrate Myeloid Leukemia 1 (MCL1), and sensitizes cancer cells to anti-tubulin chemotherapy. Concomitant FBW7 inactivation rescues the effects of TRIP12 deficiency, confirming FBW7 as an essential mediator of TRIP12 function. This work reveals an unexpected complexity of FBW7 ubiquitylation, and highlights branched ubiquitylation as an important signalling mechanism regulating protein stability.


Assuntos
Proteínas de Transporte/metabolismo , Proteína 7 com Repetições F-Box-WD/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Biocatálise , Resistencia a Medicamentos Antineoplásicos , Células HCT116 , Células HEK293 , Humanos , Lisina/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Ligação Proteica , Processamento de Proteína Pós-Traducional , Estabilidade Proteica , RNA Interferente Pequeno/metabolismo , Especificidade por Substrato , Enzimas de Conjugação de Ubiquitina/metabolismo
11.
Am J Orthod Dentofacial Orthop ; 159(4): 512-521, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33795092

RESUMO

INTRODUCTION: This study aimed to evaluate the efficiency of a newly constructed computer-based decision support system (DSS) on the basis of artificial intelligence technology and designed to plan treatment for patients with a deep overbite. METHODS: With the help of information technology, a DSS was developed specifically for treatment planning of deepbite malocclusion. The program inputs were the components and the contributing factors used commonly by the orthodontic clinicians in deepbite diagnosis. The program outputs were the treatment planning options for deepbite treatment. A total of 357 decisions made by the algorithm were evaluated for accuracy by comparing them to the actual treatment changes of 51 patients with a well-treated deepbite. RESULTS: The decisions made by the algorithm were precise, with 94.4% having a very good agreement with actual treatment changes determined using Cohen's kappa coefficient. CONCLUSIONS: The constructed DSS was shown to be an efficient tool for planning treatment of deep overbite malocclusion in the permanent dentition; thus, the artificial intelligence could be used to formulate a customized plan for orthodontic clinicians.


Assuntos
Inteligência Artificial , Má Oclusão , Algoritmos , Cefalometria , Dentição Permanente , Humanos , Má Oclusão/terapia , Mandíbula
12.
J Infect Public Health ; 14(5): 611-619, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33866129

RESUMO

BACKGROUND: The emergence and spread of SARS-CoV-2 throughout the world has created an enormous socioeconomic impact. Although there are several promising drug candidates in clinical trials, none is available clinically. Thus, the drug repurposing approach may help to overcome the current pandemic. METHODS: The main protease (Mpro) of SARS-CoV-2 is crucial for cleaving nascent polypeptide chains. Here, FDA-approved antiviral and anti-infection drugs were screened by high-throughput virtual screening (HTVS) followed by re-docking with standard-precision (SP) and extra-precision (XP) molecular docking. The most potent drug's binding was further validated by free energy calculations (Prime/MM-GBSA) and molecular dynamics (MD) simulation. RESULTS: Out of 1397 potential drugs, 157 showed considerable affinity toward Mpro. After HTVS, SP, and XP molecular docking, four high-affinity lead drugs (Iodixanol, Amikacin, Troxerutin, and Rutin) with docking energies -10.629 to -11.776kcal/mol range were identified. Among them, Amikacin exhibited the lowest Prime/MM-GBSA energy (-73.800kcal/mol). It led us to evaluate other aminoglycosides (Neomycin, Paramomycin, Gentamycin, Streptomycin, and Tobramycin) against Mpro. All aminoglycosides were bound to the substrate-binding site of Mpro and interacted with crucial residues. Altogether, Amikacin was found to be the most potent inhibitor of Mpro. MD simulations of the Amikacin-Mpro complex suggested the formation of a complex stabilized by hydrogen bonds, salt bridges, and van der Waals interactions. CONCLUSION: Aminoglycosides may serve as a scaffold to design potent drug molecules against COVID-19. However, further validation by in vitro and in vivo studies is required before using aminoglycosides as an anti-COVID-19 agent.


Assuntos
Reposicionamento de Medicamentos , Aminoglicosídeos , Antivirais/farmacologia , Humanos , Simulação de Acoplamento Molecular , Peptídeo Hidrolases , Inibidores de Proteases/farmacologia
13.
J Pharm Biomed Anal ; 200: 114078, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33901756

RESUMO

A fast, sensitive one step UPLC ESI-MS/MS method was successfully applied for the simultaneous estimation of two concurrently administrated antidiabetic drugs, Metformin (MET) and Empagliflozin (EMPA) in human plasma. Metformin-d6 (MET-d6) and Empagliflozin-d4 (EMPA-d4) were utilized as internal standards. Extraction of the analytes from the human plasma was performed through acetonitrile precipitation technique followed by freezing the precipitated plasma proteins and lipids to minimize the matrix effect. Chromatographic analysis was developed on Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 50 mm) using isocratic elution mode. A mobile phase of formic acid (0.01 %): acetonitrile (70:30 v/v) with a flow rate of 0.3 mL/min achieved optimum separation. Multiple reaction monitoring (MRM) in positive ion mode, with transitions at (m/z) 130.14 →71.08 for (MET), 451.72 →71.29 for (EMPA), 136.03 →77.02 for (MET-d6), and 455.43 → 75.05 for (EMPA-d4) was used for quantification. The obtained linearity covered the concentration ranges of 10-1500 ng/mL and 2.0-250.0 ng/mL for MET and EMPA, respectively. The run time of the proposed Method didn't exceed 3.0 min allowing faster analysis and determination of larger number of samples per day without affecting accuracy and sensitivity. The presented chromatographic method could be successfully applied in pharmacokinetics studies and therapeutic monitoring of MET and EMPA in patients' plasma administrating fixed dose combination of both drug with high reproducibility and ruggedness.

14.
Elife ; 102021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33929316

RESUMO

Paget's Disease of Bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB associated changes in DNA methylation profiles in patients' blood. Meta-analysis of data from the discovery and cross-validation set, each comprising of 116 PDB cases and 130 controls, revealed significant differences in DNA methylation at 14 CpG sites, 4 CpG islands, and 6 gene-body regions. These loci, including two characterized as functional through expression quantitative trait-methylation (eQTM) analysis, were associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on discovery samples was found to discriminate PDB cases and controls from the cross-validation with a sensitivity of 0.84, specificity of 0.81, and an area under curve of 92.8%. In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease.

15.
Viruses ; 13(5)2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925055

RESUMO

The COVID-19 pandemic has affected all individuals across the globe in some way. Despite large numbers of reported seroprevalence studies, there remains a limited understanding of how the magnitude and epitope utilization of the humoral immune response to SARS-CoV-2 viral anti-gens varies within populations following natural infection. Here, we designed a quantitative, multi-epitope protein microarray comprising various nucleocapsid protein structural motifs, including two structural domains and three intrinsically disordered regions. Quantitative data from the microarray provided complete differentiation between cases and pre-pandemic controls (100% sensitivity and specificity) in a case-control cohort (n = 100). We then assessed the influence of disease severity, age, and ethnicity on the strength and breadth of the humoral response in a multi-ethnic cohort (n = 138). As expected, patients with severe disease showed significantly higher antibody titers and interestingly also had significantly broader epitope coverage. A significant increase in antibody titer and epitope coverage was observed with increasing age, in both mild and severe disease, which is promising for vaccine efficacy in older individuals. Additionally, we observed significant differences in the breadth and strength of the humoral immune response in relation to ethnicity, which may reflect differences in genetic and lifestyle factors. Furthermore, our data enabled localization of the immuno-dominant epitope to the C-terminal structural domain of the viral nucleocapsid protein in two independent cohorts. Overall, we have designed, validated, and tested an advanced serological assay that enables accurate quantitation of the humoral response post natural infection and that has revealed unexpected differences in the magnitude and epitope utilization within a population.

16.
Pediatr Diabetes ; 22(4): 667-674, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33715298

RESUMO

OBJECTIVE: To identify culturally appropriate psychological screening measures for children and adolescents with type 1 diabetes in Qatar, determine rates of depressive and anxiety symptoms in a clinical sample, and examine associations between screening measures, demographic variables, medical characteristics, and diabetes treatment outcomes, specifically HbA1c. METHODS: A total of 150 participants with type 1 diabetes aged 10-17 were recruited. Participants were Arabic or English speaking and of Qatari and non-Qatari nationality. Participants completed the Mood and Feelings Questionnaire (child and parent proxy form), the Spence Children's Anxiety Scale, and the Pediatric Quality of Life, Diabetes version (child and parent proxy form). Glycosylated hemoglobin (HbA1c) on the date of the testing was recorded. RESULTS: Approximately ten percent (10.2%) of children and adolescents scored above the cutoff score of 27 indicating clinically significant depressive symptoms, and 12.8% of parents rated their child above the respective cutoff score of 21 for the parent proxy form. Further, 36% of the sample reported clinically significant anxiety symptoms, scoring above the cutoff score of 50. Parent report on their child's quality of life predicted HbA1c (F[6, 140] = 5.42, p = 0.000); B = -0.05, p = 0.002). CONCLUSIONS: Rates of depressive and anxiety symptoms are comparable to those observed in western countries. Thus, systematic screening for depression and anxiety in children and adolescents with type 1 diabetes should be implemented in Qatar. This will help inform decisions to refer to mental health services and thus provide more integrated care, possibly improving treatment outcomes.

17.
J Bone Miner Res ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33724536

RESUMO

Early onset familial Paget's disease of bone (EoPDB), familial expansile osteolysis, and expansile skeletal hyperphosphatasia are related disorders caused by insertion mutations in exon 1 of the TNFRSF11A gene, which encodes receptor activator of nuclear factor κB (RANK) protein. To understand the mechanisms underlying these disorders, we developed a mouse model carrying the 75dup27 mutation which causes EoPDB. Mice heterozygous for the mutation (Tnfrsf11a75dup27/- ) developed a PDB-like disorder with focal osteolytic lesions in the hind limbs with increasing age. Treatment of these mice with zoledronic acid completely prevented the development of lesions. Studies in vitro showed that RANK ligand (RANKL)-induced osteoclast formation and signaling was impaired in bone marrow cells from Tnfrsf11a75dup27/- animals, but that osteoclast survival was increased independent of RANKL stimulation. Surprisingly, Tnfrsf11a75dup27/75dup27 homozygotes had osteopetrosis at birth, with complete absence of osteoclasts. Bone marrow cells from these mice failed to form osteoclasts in response to RANKL and macrophage colony-stimulating factor (M-CSF) stimulation. This intriguing study has shown that in heterozygous form, the 75dup27 mutation causes focal osteolytic lesions in vivo reminiscent of the human disorder and extends osteoclast survival independently of RANKL signaling. In homozygous form, however, the mutation causes osteopetrosis due to failure of osteoclast formation and insensitivity to RANKL stimulation. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..

18.
Mar Drugs ; 19(2)2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33670308

RESUMO

To tackle the growing problem of antibiotic resistance, it is essential to identify new bioactive compounds that are effective against resistant microbes and safe to use. Natural products and their derivatives are, and will continue to be, an important source of these molecules. Sea sponges harbour a diverse microbiome that co-exists with the sponge, and these bacterial communities produce a rich array of bioactive metabolites for protection and resource competition. For these reasons, the sponge microbiota constitutes a potential source of clinically relevant natural products. To date, efforts in bioprospecting for these compounds have focused predominantly on sponge specimens isolated from shallow water, with much still to be learned about samples from the deep sea. Here we report the isolation of a new Micromonospora strain, designated 28ISP2-46T, recovered from the microbiome of a mid-Atlantic deep-sea sponge. Whole-genome sequencing reveals the capacity of this bacterium to produce a diverse array of natural products, including kosinostatin and isoquinocycline B, which exhibit both antibiotic and antitumour properties. Both compounds were isolated from 28ISP2-46T fermentation broths and were found to be effective against a plethora of multidrug-resistant clinical isolates. This study suggests that the marine production of isoquinocyclines may be more widespread than previously supposed and demonstrates the value of targeting the deep-sea sponge microbiome as a source of novel microbial life with exploitable biosynthetic potential.

20.
Biomed Pharmacother ; 138: 111417, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33752057

RESUMO

Combretastatin A-4 (CA-4) received significant interest as a potential anticancer agent in recent years. Several CA-4 analogs were synthesized and investigated to enhance the activity or solve the in vivo decreased activity of CA-4. AIM: The present study aims to investigate the chemotherapeutic and the antiproliferative effects of the mono and the dual therapy of the newly synthesized CA-4 analogs OMA1520 and OMA1774 against hepatocellularcarcinoma (HCC) induced in male adult rats by N-methylnitrosourea (MNU). METHODS: 50 male rats were divided into 5 groups of 10 animals in each group. Group I: normal healthy control; group II: MNU treated group, group III: MNU animals treated by OMA1520, group IV: MNU animals treated by OMA1774, and group V: MNU animals treated by both OMA1520 and OMA1774. The rats were assessed for liver cancer progression or inhibition by evaluating the histopathological, immunohistochemical, biochemical, and antioxidant enzyme status. RESULTS: The present work indicated that OMA1520 and OMA1774 possessed substantial chemotherapeutic efficiency against HCC. The histological and immunohistochemical examinations of liver tissues confirmed the biochemical sera data. Also, they diminished the cytotoxic effects of MNU and restored the normal histological hepatic architecture. Both analogs restored the normal levels of liver enzymes and functions and revealed potential antioxidant effects. OMA1520 and OMA1774 reduced the inflammatory and tumor markers' elevated expressions in serum. CONCLUSION: Substantial evidence in our results suggests that both CA-4 analogs could be possible alternative anticancer agents, and their co-administration provides a synergistic activity.

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