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1.
Ann Card Anaesth ; 27(2): 165-168, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38607882

RESUMO

ABSTRACT: Mediastinal masses pose one of the great challenges for any anesthesiologist during airway maintenance, underlining the need to devise a well-formulated plan to avoid perioperative complications. As a general rule, such patients are managed with spontaneous ventilation without the use of muscle relaxants and awake intubation. We report a case of a 66-year-old male with severe dyspnea, having a very large invasive anterior mediastinal mass, causing left lung collapse for urgent debulking surgery. The tracheobronchial compromise was ruled out using three-dimensional reconstruction on computed tomography imaging (virtual bronchoscopy) and that helped in using general anesthesia with muscle relaxation for subsequent endotracheal intubation and surgery.


Assuntos
Manuseio das Vias Aéreas , Broncoscopia , Masculino , Humanos , Idoso , Intubação Intratraqueal , Anestesia Geral , Anestesiologistas
2.
Cureus ; 16(1): e52618, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38374850

RESUMO

OBJECTIVE:  Effect of the COVID-19 pandemic on knowledge, attitude, and practices toward antenatal care among antenatal women. DESIGN:  Prospective observational study. METHOD: After taking written and informed consent, 3000 term/near-term SARS CoV2-negative antenatal women admitted to the hospital for emergency were enrolled; excluding those in advance labour or critically ill. An interview was conducted and a knowledge, attitude, and practices (KAP) questionnaire was filled out based on verbatim answers. All women were then given individualized antenatal and postnatal care as per hospital protocols and discharged accordingly. The data obtained during the study was recorded on predesigned case proforma and analysed at the end of the study using the SPSS v. 23 software, after the application of appropriate statistical tests. MAIN RESULT: All women knew about the pandemic and its signs and symptoms along with precautions to be taken. Most of the women 2652 (88.4%) thought that they were at increased risk of contracting an infection during pregnancy and 2208 (73.6%) thought that coronavirus can harm the baby and will increase the risk of pregnancy. Awareness of nearby health facilities providing antenatal care was in 71.2% and 94% were aware of functional outpatient department services but only 1.4% were aware of teleconsultation services. About 2094 women have had any ANC visits. All of them knew that taking iron, Ca and vitamin supplements and getting an ultrasound and investigations were necessary but only 1524 (50.8%) took these supplements regularly, 1752 (58.4%) got their ultrasound done and 41.6% got investigations done. Two thousand four hundred thirty-six (81.2%) women had this fear that they would contract COVID-19 infection during their visit to the hospital. All the respondents of our study wanted to have hospital delivery and knew that it was necessary to have ANC registration and none of them wanted to have home delivery. CONCLUSION: Mastering correct knowledge will foster a positive attitude among antenatal women and will not only prevent disease transmission but also improve pregnancy outcomes.

3.
Microbiol Spectr ; 11(6): e0158823, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37874174

RESUMO

IMPORTANCE: Difficult-to-treat pulmonary infections caused by nontuberculous mycobacteria of the Mycobacterium abscessus group have been steadily increasing in the USA and globally. Owing to the relatively recent recognition of M. abscessus as a human pathogen, basic and translational research to address critical gaps in diagnosis, treatment, and prevention of diseases caused by this microorganism has been lagging behind that of the better-known mycobacterial pathogen, Mycobacterium tuberculosis. To begin unraveling the molecular mechanisms of pathogenicity of M. abscessus, we here focus on the study of a two-component regulator known as PhoPR which we found to be under strong evolutionary pressure during human lung infection. We show that PhoPR is activated at acidic pH and serves to regulate a defined set of genes involved in host adaptation. Accordingly, clinical isolates from chronically infected human lungs tend to hyperactivate this regulator enabling M. abscessus to escape macrophage killing.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Mycobacterium tuberculosis , Humanos , Adaptação ao Hospedeiro , Concentração de Íons de Hidrogênio , Mutação , Mycobacterium abscessus/genética , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium tuberculosis/genética , Virulência/genética , Proteínas Quinases/genética , Proteínas Quinases/metabolismo
4.
J Indian Soc Pedod Prev Dent ; 40(1): 23-29, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35439879

RESUMO

Introduction: Restoring a proximal lesion in primary tooth has met with many challenges which has led to evolution of many materials. An alternative to Glass Ionomer Cements which has fluoride releasing capacity, offers good bond strength and is esthetic have been long looked for. Aim: This study aimed to compare the clinical performance of GIC and Cention N in proximal restorations of primary molars. Materials and Methodology: A prospective study was conducted on 154 primary molars in patients aged between 5 and 8 years using a split-mouth design. Patients were divided into two groups. Control group restored with GIC and study group received Cention N. Both groups were assessed at baseline 3, 6 and 9 months according to Ryge criteria and data was statistically analysed using Fisher's Exact. Results: Statistically significant difference was found between GIC and Cention N restorations for color match at baseline and color stability at 3 months (P < 0.001), while the other parameters did not show any significant difference among the two restorative materials. Conclusion: Cention N can be used as a suitable alternative to GIC for restoring Class II restorations in primary molars.


Assuntos
Cárie Dentária , Cimentos de Ionômeros de Vidro , Criança , Pré-Escolar , Resinas Compostas/química , Materiais Dentários , Restauração Dentária Permanente , Cimentos de Ionômeros de Vidro/química , Cimentos de Ionômeros de Vidro/uso terapêutico , Humanos , Dente Molar , Estudos Prospectivos , Dente Decíduo
5.
Mycoses ; 65(1): 13-23, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34378240

RESUMO

BACKGROUND: There has been an alarming increase in the prevalence of chronic, recurrent and steroid modified dermatophytosis of the glabrous skin in the recent years in India. There is paucity of literature on the magnitude of this major public health problem. OBJECTIVE: To estimate the prevalence of dermatophytosis and clinico-epidemiological features of chronic and recurrent dermatophytosis (CRD) across India and to evaluate the associated risk factors. METHODS: This is a multicentric descriptive cross-sectional study conducted in 13 centres situated across India in two phases during dry and rainy seasons. All consecutive patients presenting with dermatophytosis were screened during the study period of 14 consecutive working days. Patients with CRD of the glabrous skin as per the case definition were included after exclusion of isolated hair and nail infections. Demography, clinical findings and results of potassium hydroxide wet mount were recorded. RESULTS AND CONCLUSION: A total of 41,421 patients were screened, out of which 7174 (17.31%) patients had glabrous dermatophytosis. CRD was observed in 1999 (27.86%) patients with 78.08% and 21.95% of chronic and recurrent dermatophytosis, respectively. Family history was present in 50.03% of patients. History of sharing of fomites was present in 50.37% of them. Synthetic tight clothes were worn by 43.47%, while 50.9% gave history of misuse of topical corticosteroid creams. Multiple site involvement was common (69.58%) with tinea cruris (79.99%) and tinea corporis (75.69%) being the most common clinical types. CRD is associated with sharing of fomites, topical corticosteroid misuse and involvement of multiple sites.


Assuntos
Tinha , Estudos Transversais , Glucocorticoides , Humanos , Índia/epidemiologia , Recidiva , Tinha/epidemiologia
6.
ACS Omega ; 6(25): 16266-16272, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34235296

RESUMO

Diethyl sulfate (DES)-based chemical mutagenesis was applied on different fungal strains with the aim of diversifying the secondary metabolites. The mutant strain (VRE-MT1) of Penicillium oxalicum was subjected to dereplication (LCMS-based) and isolation of natural products, resulting in obtaining 10 molecules of bioactive potential. Metabolites, viz. tuckolide, methylpenicinoline, 2-acetyl-3,5-dihydroxy-4,6-dimethylbenzeneacetic acid, penicillixanthone A, brefeldin A 7-ketone, and antibiotic FD 549, were observed for the first time from P. oxalicum. The results of antimicrobial activity reveal that the compounds N-[2-(4-hydroxyphenyl)ethenyl]formamide, methylpenicinoline, and penipanoid A have potent antibacterial activity against Bacillus subtilis (ATCC 6633) with minimum inhibitory concentration (MIC) values of 16, 64, and 16 µM, respectively, and the compounds N-[2-(4-hydroxyphenyl)ethenyl]formamide, methylpenicinoline, and penipanoid A were found active against Escherichia coli (ATCC 25922), with MIC values of 16, 64, and 16 µM, respectively. Also, the metabolites N-[2-(4-hydroxyphenyl)ethenyl]formamide and tuckolide showed effective antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid scavenging assays. The mutant VRE-MT1 was found to have 8.34 times higher quantity of N-[2-(4-hydroxyphenyl)ethenyl]formamide as compared to the mother strain. The DES-based mutagenesis strategy has been found to be a potent tool to diversify the secondary metabolites in fungi.

7.
J Cutan Aesthet Surg ; 14(1): 93-100, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34084015

RESUMO

CONTEXT: Onychomycosis (OM) accounts for 20%-40% of all nail disorders. Slow growth of nails, resistance to antifungal drugs, their side effects, and drug interactions limit treatment options. Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser is approved for nail clearance of OM, however conflicting reports exist in literature about its efficacy. This study was conducted to compare the efficacy of Q-switched Nd:YAG laser. AIM: The aim of this study was to find the efficacy of Q-switched Nd:YAG laser (1064 nm) management of OM as monotherapy in comparison to itraconazole. SETTINGS AND DESIGN: A randomized parallel group, outcome assessor trial was conducted over 18 months from July 1, 2015 to December 31, 2016, at skin center of a tertiary care hospital. SUBJECTS AND METHODS: In the first group, patients of OM were administered 12 weekly sessions of the laser. Second group was administered itraconazole 200 mg twice a day for 1 week per month for the 3 months. Confirmed cases of OM, who had not received treatment 6 months before presentation, were selected and randomly allocated to two groups of 50 each. Onychomycosis severity index (OSI) and visual analog scale (VAS) score were used to assess nail involvement at the start of study, 3 months and 1 year after enrollment. STATISTICAL ANALYSIS: Clinical profile of patients was analyzed by chi-square test for qualitative variables. For comparison of quantitative variables, Student t test was performed. A 5% probability level was considered as statistically significant (P < 0.05). RESULTS: VAS and OSI showed statistically significant improvement at 3 and 12 months in Group I, while resulting in faster clearance with laser; OSI was comparable in both groups at 12 months. Mycological cure was significantly higher in Group I. Both dermatophytes as well as non-dermatophytes responded well to laser treatment, whereas non-dermatophytes responded better to laser. CONCLUSIONS: Q-switched Nd:YAG laser is effective in inducing nail clearance in OM and is better than itraconazole in managing non-dermatophyte OM.

8.
Science ; 372(6541)2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33926925

RESUMO

Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as Mycobacterium tuberculosis, have evolved to cause transmissible human infection. By analyzing the recent emergence and spread of the environmental organism M. abscessus through the global cystic fibrosis population, we have defined key, generalizable steps involved in the pathogenic evolution of mycobacteria. We show that epigenetic modifiers, acquired through horizontal gene transfer, cause saltational increases in the pathogenic potential of specific environmental clones. Allopatric parallel evolution during chronic lung infection then promotes rapid increases in virulence through mutations in a discrete gene network; these mutations enhance growth within macrophages but impair fomite survival. As a consequence, we observe constrained pathogenic evolution while person-to-person transmission remains indirect, but postulate accelerated pathogenic adaptation once direct transmission is possible, as observed for M. tuberculosis Our findings indicate how key interventions, such as early treatment and cross-infection control, might restrict the spread of existing mycobacterial pathogens and prevent new, emergent ones.


Assuntos
Doenças Transmissíveis Emergentes/microbiologia , Evolução Molecular , Aptidão Genética , Pulmão/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/genética , Mycobacterium abscessus/patogenicidade , Pneumonia Bacteriana/microbiologia , Doenças Transmissíveis Emergentes/transmissão , Conjuntos de Dados como Assunto , Epigênese Genética , Transferência Genética Horizontal , Genoma Bacteriano , Humanos , Mutação , Infecções por Mycobacterium não Tuberculosas/transmissão , Pneumonia Bacteriana/transmissão , Virulência/genética
9.
PLoS Pathog ; 17(3): e1009452, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33740020

RESUMO

Tuberculosis caused by Mycobacterium tuberculosis (Mtb) is a significant public health concern, exacerbated by the emergence of drug-resistant TB. To combat the host's dynamic environment, Mtb encodes multiple DNA repair enzymes that play a critical role in maintaining genomic integrity. Mtb possesses a GC-rich genome, rendering it highly susceptible to cytosine deaminations, resulting in the occurrence of uracils in the DNA. UDGs encoded by ung and udgB initiate the repair; hence we investigated the biological impact of deleting UDGs in the adaptation of pathogen. We generated gene replacement mutants of uracil DNA glycosylases, individually (RvΔung, RvΔudgB) or together (RvΔdKO). The double KO mutant, RvΔdKO exhibited remarkably higher spontaneous mutation rate, in the presence of antibiotics. Interestingly, RvΔdKO showed higher survival rates in guinea pigs and accumulated large number of SNPs as revealed by whole-genome sequence analysis. Competition assays revealed the superior fitness of RvΔdKO over Rv, both in ex vivo and in vivo conditions. We propose that compromised DNA repair results in the accumulation of mutations, and a subset of these drives adaptation in the host. Importantly, this property allowed us to utilize RvΔdKO for the facile identification of drug targets.


Assuntos
Adaptação Fisiológica/genética , Reparo do DNA/fisiologia , Especificidade de Hospedeiro/genética , Mycobacterium tuberculosis/genética , Animais , Cobaias , Camundongos
10.
J Orthop Case Rep ; 11(8): 33-36, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35004371

RESUMO

INTRODUCTION: Xanthomas are defined as benign lesions characterized by an accumulation of lipid-laden macrophages that develop in the cutis and subcutaneous tissue. Xanthomas are classified as eruptive, tuberous, tendinous, or planar depending on their location and clinical appearance. Co-existence of both tuberous and tendinous forms in an atypical large-sized pattern is a rarity and presented herewith. CASE PRESENTATION: A 48-year-old male patient presented with multiple large masses in his elbows, knees, Achilles tendons, feet, and hands. The largest swellings measured 12 cm × 10 cm in dimensions. The blood workup of the patient showed an elevated level of low-density lipoprotein cholesterol and was subsequently diagnosed with Type IIa familial hypercholesterolemia and multiple large co-existing tuberous and tendinous xanthomas which is a rare clinical presentation. Local surgical excision was performed to remove the symptomatic massive xanthomas from the elbows, knees, and feet. Histological analysis of the surgical specimens confirmed the clinical diagnosis of xanthomas. CONCLUSION: Tuberous and tendinous xanthomas can co-exist in the same patient, including atypical large-sized forms. Usually, patients with xanthomas have some underlying metabolic lipid derangement and a cardiology workup to detect future cardiac risk is warranted. Intervention at an early stage can prevent the formation of disfiguring xanthomas in patients with underlying lipid disorder. The case also highlights a multi-disciplinary approach to such rare clinical presentations.

11.
Biotechnol Adv ; 40: 107521, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31953204

RESUMO

Natural products (NPs) are considered as a cornerstone for the generation of bioactive leads in drug discovery programs. However, one of the major limitations of NP drug discovery program is "rediscovery" of known compounds, thereby hindering the rate of drug discovery efficiency. Therefore, in recent years, to overcome these limitations, a great deal of attention has been drawn towards understanding the role of microorganisms' co-culture in inducing novel chemical entities. Such induction could be related to activation of genes which might be silent or expressed at very low levels (below detection limit) in pure-strain cultures under normal laboratory conditions. In this review, chemical diversity of compounds isolated from microbial co-cultures, is discussed. For this purpose, chemodiversity has been represented as a chemical-structure network based on the "Tanimoto Structural Similarity Index". This highlights the huge structural diversity induced by microbial co-culture. In addition, the current trends in microbial co-culture research are highlighted. Finally, the current challenges (1 - induction monitoring, 2 - reproducibility, 3 - growth time effect and 4 - up-scaling for isolation purposes) are discussed. The information in this review will support researchers to design microbial co-culture strategies for future research efforts. In addition, guidelines for co-culture induction reporting are also provided to strengthen future reporting in this NP field.


Assuntos
Técnicas de Cocultura , Produtos Biológicos , Descoberta de Drogas , Reprodutibilidade dos Testes
12.
Anesth Essays Res ; 14(2): 326-330, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33487837

RESUMO

BACKGROUND: With increasing knee replacement surgeries, there has been a constant search for effective pain control modality. AIMS: We compared the analgesic effect of femoral nerve block (FNB) alone with combined femoral and sciatic nerve block (SNB) for postoperative pain management after total knee arthroplasty (TKA). SETTING AND DESIGN: This was a prospective observational study. METHODS: A total of 150 adult patients of American Society of Anesthesiologists physical status class I and II scheduled for elective TKA under spinal anesthesia with 3.4-mL bupivacaine 0.5% and 20-µg fentanyl were randomly allocated to two groups. Group F patients received a single shot FNB with 20 ml 0.375% ropivacaine and Group FS patients received combined FNB with 20 mL of 0.375% ropivacaine and SNB with 40 ml of 0.375% ropivacaine at the end of surgery. The primary outcome was the change in Numeric Rating Scale (NRS) scores between Groups F and FS at 6, 12, 18, 24, and 48 h later. The secondary outcome was total doses of opioid required in both groups. RESULTS: The demographic data were comparable in both groups. The NRS scores were higher and statistically significant in Group F than that in Group FS at all five measured time points (P < 0.00001), and the total pain score with a mean of 15.43 in Group F and a mean of 9.61 in Group FS was statistically significant. Significantly more opioid consumption was seen postoperatively in Group F as compared to Group FS at 12, 18, 24, and 48 h as depicted by P < 0.00001. CONCLUSIONS: We conclude that the FNB, when combined with SNB, shows superior results than femoral block alone. SNB reduced pain scores and opiate consumption postoperatively up to 48 h.

13.
J Card Surg ; 34(11): 1396-1398, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31441546

RESUMO

Iatrogenic intraoperative coronary artery ostial occlusion is quite rare and a dangerous complication of aortic valve replacement. Intraoperative vigilance and prompt intervention are required to manage this fatal complication. A case report of a 48-year-old female with normal coronaries who underwent aortic valve replacement and had right ventricle distension is described here. It seemed that the cause which led to right coronary ostial obstruction was due to prosthesis aortic root mismatch and it required bypass with a vein graft. Computed tomographic angiography of aortic root showed abutting of right coronary ostium by the aortic valve prosthesis.


Assuntos
Aorta/cirurgia , Arteriopatias Oclusivas/etiologia , Implante de Prótese Vascular/efeitos adversos , Vasos Coronários , Complicações Intraoperatórias/etiologia , Feminino , Humanos , Pessoa de Meia-Idade
14.
Sci Rep ; 9(1): 10912, 2019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358794

RESUMO

The RecX protein has attracted considerable interest because the recX mutants exhibit multiple phenotypes associated with RecA functions. To further our understanding of the functional relationship between recA and recX, the effect of different stress treatments on their expression profiles, cell yield and viability were investigated. A significant correlation was found between the expression of Mycobacterium smegmatis recA and recX genes at different stages of growth, and in response to different stress treatments albeit recX exhibiting lower transcript and protein abundance at the mid-log and stationary phases of the bacterial growth cycle. To ascertain their roles in vivo, a targeted deletion of the recX and recArecX was performed in M. smegmatis. The growth kinetics of these mutant strains and their sensitivity patterns to different stress treatments were assessed relative to the wild-type strain. The deletion of recA affected normal cell growth and survival, while recX deletion showed no significant effect. Interestingly, deletion of both recX and recA genes results in a phenotype that is intermediate between the phenotypes of the ΔrecA mutant and the wild-type strain. Collectively, these results reveal a previously unrecognized role for M. smegmatis recX and support the notion that it may regulate a subset of the yet unknown genes involved in normal cell growth and DNA-damage repair.


Assuntos
Proteínas de Bactérias/fisiologia , Mycobacterium smegmatis/crescimento & desenvolvimento , Recombinases Rec A/fisiologia , Proteínas de Bactérias/genética , Reparo do DNA , Regulação Bacteriana da Expressão Gênica , Mycobacterium smegmatis/genética , Recombinases Rec A/genética , Deleção de Sequência
15.
J Bacteriol ; 201(12)2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-30962357

RESUMO

A hallmark feature of Mycobacterium tuberculosis pathogenesis lies in the ability of the pathogen to survive within macrophages under a stressful environment. Thus, coordinated regulation of stress proteins is critically important for an effective adaptive response of M. tuberculosis, the failure of which results in elevated immune recognition of the tubercle bacilli with reduced survival during chronic infections. Here, we show that virulence regulator PhoP impacts the global regulation of heat shock proteins, which protect M. tuberculosis against stress generated by macrophages during infection. Our results identify that in addition to classical DNA-protein interactions, newly discovered protein-protein interactions control complex mechanisms of expression of heat shock proteins, an essential pathogenic determinant of M. tuberculosis While the C-terminal domain of PhoP binds to its target promoters, the N-terminal domain of the regulator interacts with the C-terminal end of the heat shock repressors. Remarkably, our findings delineate a regulatory pathway which involves three major transcription factors, PhoP, HspR, and HrcA, that control in vivo recruitment of the regulators within the target genes and regulate stress-specific expression of heat shock proteins via protein-protein interactions. The results have implications on the mechanism of regulation of PhoP-dependent stress response in M. tuberculosisIMPORTANCE The regulation of heat shock proteins which protect M. tuberculosis against stress generated by macrophages during infection is poorly understood. In this study, we show that PhoP, a virulence regulator of the tubercle bacilli, controls heat shock-responsive genes, an essential pathogenic determinant of M. tuberculosis Our results unravel that in addition to classical DNA-protein interactions, complex mechanisms of regulation of heat shock-responsive genes occur through multiple protein-protein interactions. Together, these findings delineate a fundamental regulatory pathway where transcription factors PhoP, HspR, and HrcA interact with each other to control stress-specific expression of heat shock proteins.


Assuntos
Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Proteínas de Choque Térmico/genética , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade , Humanos , Macrófagos/microbiologia , Regiões Promotoras Genéticas , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Virulência
16.
Eur J Pharm Sci ; 121: 47-58, 2018 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-29777858

RESUMO

In recent years scientific community has drawn a great deal of attention towards understanding the enigma of cluster of differentiation-44 (CD44) in order to deliver therapeutic agents more selectively towards tumor tissues. Moreover, its over-expression in variety of solid tumors has attracted drug delivery researchers to target this receptor with nanomedicines. Conventional nanomedicines based on biodegradable polymers such as poly(lactide-co-glycolide) (PLGA) are often associated with insufficient cellular uptake by cancer cells, due to lack of active targeting moiety on their surface. Therefore, to address this limitation, CD44 targeted PLGA nanomedicines has gained considerable interest for enhancing the efficacy of chemotherapeutic agents. In this review, we have elaborately discussed the recent progress in the design and synthesis of CD44 targeted PLGA nanomedicines used to improve tumor-targeted drug delivery. We have also discussed strategies based on co-targeting of CD44 with other targeting moieties such as folic acid, human epidermal growth factor 2 (HER2), monoclonal antibodies using PLGA based nanomedicines.


Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Receptores de Hialuronatos/fisiologia , Nanopartículas/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Animais , Humanos , Receptores de Hialuronatos/química , Terapia de Alvo Molecular , Nanomedicina , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Conformação Proteica
17.
Bioorg Med Chem Lett ; 28(12): 2217-2221, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29759727

RESUMO

Addition of the valproic acid (histone deacetylases inhibitor) to a culture of an endophytic fungus Diaporthe sp. harbored from Datura inoxia significantly altered its secondary metabolic profile and resulted in the isolation of three novel compounds, identified as xylarolide A (1), diportharine A (2) and xylarolide B (3) along with one known compound xylarolide (4). The structures of all the compounds (1-4) were determined by detailed analysis of 1D and 2D NMR spectroscopic data. The relative configurations of compounds 1-3 were determined with the help of NOESY data and comparison of optical rotations with similar compounds with established stereochemistry. All the isolated compounds were screened for antibacterial, antioxidant and cytotoxic activities. Xylarolide A (1) and xylarolide (4) displayed significant growth inhibition of MIAPaCa-2 with an IC50 of 20 and 32 µM respectively and against PC-3 with an IC50 of 14 and 18 µM respectively. Moreover, compound 1 displayed significant DPPH scavenging activity with EC50 of 10.3 µM using ascorbic acid as a positive control.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Ascomicetos/química , Datura/microbiologia , Peptídeos Cíclicos/farmacologia , Ácido Valproico/farmacologia , Antibacterianos/química , Antibacterianos/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Ascomicetos/crescimento & desenvolvimento , Ascomicetos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Datura/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Conformação Molecular , Peptídeos Cíclicos/química , Peptídeos Cíclicos/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade , Ácido Valproico/química
18.
J Biol Chem ; 293(17): 6497-6516, 2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29530985

RESUMO

The cell wall of Mycobacterium tuberculosis (Mtb) is a complex structure that protects the pathogen in hostile environments. Peptidoglycan (PG), which helps determine the morphology of the cell envelope, undergoes substantial remodeling under stress. This meshwork of linear chains of sugars, cross-linked through attached peptides, is generated through the sequential action of enzymes termed transglycosylases and transpeptidases. The Mtb genome encodes two classical transglycosylases and four transpeptidases, the functions of which are not fully elucidated. Here, we present work on the yet uncharacterized transpeptidase PbpA and a nonclassical transglycosylase RodA. We elucidate their roles in regulating in vitro growth and in vivo survival of pathogenic mycobacteria. We find that RodA and PbpA are required for regulating cell length, but do not affect mycobacterial growth. Biochemical analyses show PbpA to be a classical transpeptidase, whereas RodA is identified to be a member of an emerging class of noncanonical transglycosylases. Phosphorylation of RodA at Thr-463 modulates its biological function. In a guinea pig infection model, RodA and PbpA are found to be required for both bacterial survival and formation of granuloma structures, thus underscoring the importance of these proteins in mediating mycobacterial virulence in the host. Our results emphasize the fact that whereas redundant enzymes probably compensate for the absence of RodA or PbpA during in vitro growth, the two proteins play critical roles for the survival of the pathogen inside its host.


Assuntos
Proteínas de Bactérias , Glicosiltransferases , Granuloma do Sistema Respiratório , Viabilidade Microbiana , Mycobacterium tuberculosis , Peptidil Transferases , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Feminino , Genoma Bacteriano , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Granuloma do Sistema Respiratório/enzimologia , Granuloma do Sistema Respiratório/genética , Granuloma do Sistema Respiratório/patologia , Cobaias , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/enzimologia , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade , Peptidil Transferases/genética , Peptidil Transferases/metabolismo , Tuberculose/enzimologia , Tuberculose/genética , Tuberculose/patologia
19.
Drug Discov Today ; 23(5): 1115-1125, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29481876

RESUMO

In recent years, research has focused on the development of smart nanocarriers that can respond to specific stimuli. Among the various stimuli-responsive platforms for cancer therapy, near-infrared (NIR) light (700-1000nm)-responsive nanocarriers have gained considerable interest because of their deeper tissue penetration capacity, precisely controlled drug release, and minimal damage towards normal tissues. In this review, we outline various therapeutic applications of NIR-responsive nanocarriers in drug delivery, photothermal therapy (PTT), photodynamic therapy (PDT), and bioimaging. We also highlight recent trends towards NIR-responsive combinatorial therapy and multistimuli-responsive nanocarriers for improving therapeutic outcomes.


Assuntos
Portadores de Fármacos/administração & dosagem , Raios Infravermelhos , Nanoestruturas/administração & dosagem , Neoplasias/tratamento farmacológico , Animais , Portadores de Fármacos/efeitos da radiação , Humanos , Nanoestruturas/efeitos da radiação
20.
Ann N Y Acad Sci ; 1421(1): 5-18, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29377164

RESUMO

Betulinic acid (BA), a naturally occurring plant-derived pentacyclic triterpenoid, has gained attention in recent years owing to its broad-spectrum biological and medicinal properties. Despite the pharmacological activity of BA, it has been associated with some drawbacks, such as poor aqueous solubility and short half-life in vivo, which limit therapeutic application. To solve these problems, much work in recent years has focused on enhancing BA's aqueous solubility, half-life, and efficacy by using nanoscale drug delivery systems. Several different kinds of nanoscale delivery systems-including polymeric nanoparticles, magnetic nanoparticles, liposomes, polymeric conjugates, nanoemulsions, cyclodextrin complexes, and carbon nanotubes-have been developed for the delivery of BA. Here, we focus on the recent developments of novel nanoformulations used to deliver BA in order to improve its efficacy.


Assuntos
Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Triterpenos/uso terapêutico , Meia-Vida , Humanos , Triterpenos Pentacíclicos , Solubilidade , Triterpenos/química , Triterpenos/farmacocinética , Ácido Betulínico
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