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1.
J Insect Physiol ; 156: 104664, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38897288

RESUMO

Like other lepidopteran insects, males of the tobacco cutworm moth, Spodoptera litura produce two kinds of spermatozoa, eupyrene (nucleate) and apyrene (anucleate) sperm. Formed in the testis, both kinds of sperm are released into the male reproductive tract in an immature form and are stored in the duplex region of the tract. Neither type of sperm is motile at this stage. When stored apyrene sperm from the duplex are treated in vitro with an extract of the prostatic region of the male tract, or with mammalian trypsin, they become motile; activation is greater and achieved more rapidly with increasing concentration of extract or enzyme. The activating effect of prostatic extract is blocked by soybean trypsin inhibitor (SBTI), also in a dose-dependent way. These results suggest that the normal sperm-activating process is due to an endogenous trypsin-like protease produced in the prostatic region. Proteomic analysis of S. litura prostatic extracts revealed a Trypsin-Like Serine Protease, TLSP, molecular weight 27 kDa, whose 199-residue amino acid sequence is identical to that of a predicted protein from the S. litura genome and is highly similar to predicted proteins encoded by genes in the genomes of several other noctuid moth species. Surprisingly, TLSP is only distantly related to Serine Protease 2 (initiatorin) of the silkmoth, Bombyx mori, the only identified lepidopteran protein so far shown to activate sperm. TLSP has features typical of secreted proteins, probably being synthesized as an inactive precursor zymogen, which is later activated by proteolytic cleavage. cDNA was synthesized from total RNA extracted from the prostatic region and was used to examine TLSP expression using qPCR. tlsp mRNA was expressed in both the prostatic region and the accessory glands of the male tract. Injection of TLSP-specific dsRNA into adult males caused a significant reduction after 24 h in tlsp mRNA levels in both locations. The number of eggs laid by females mated to adult males that were given TLSP dsRNA in 10 % honey solution, and the fertility (% hatched) of the eggs were reduced. Injecting pupae with TLSP dsRNA caused the later activation of apyrene sperm motility by adult male prostatic extracts to be significantly reduced compared to controls. Exposure of S. litura pupae to ionizing radiation significantly reduced expression of tlsp mRNA in the prostatic part and accessory gland of irradiated males in both the irradiated generation and also in their (unirradiated) F1 progeny. The implications of these findings for the use of the inherited sterility technique for the control of S. litura and other pest Lepidoptera are discussed.


Assuntos
Proteínas de Insetos , Espermatozoides , Spodoptera , Animais , Masculino , Spodoptera/genética , Spodoptera/enzimologia , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Espermatozoides/efeitos da radiação , Interferência de RNA , Sequência de Aminoácidos , Genitália Masculina/metabolismo , Genitália Masculina/efeitos da radiação , Proteômica , Serina Proteases/metabolismo , Serina Proteases/genética , Radiação Ionizante , Serina Endopeptidases/metabolismo , Serina Endopeptidases/genética , Transcriptoma
2.
Asian Pac J Cancer Prev ; 25(4): 1113-1119, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38679970

RESUMO

BACKGROUND: Sentinel lymph node (SLN) is the first lymph node to drain the lymph from a particular region involved by cancer. The commonly performed intraoperative methods for SLN evaluation are touch imprint cytology (TIC) and frozen section (FS). The present study aimed to determine the sensitivity, specificity and accuracy of TIC and FS with histopathological diagnosis as gold standard. MATERIALS AND METHODS: The nodes were bissected along their long axis and wet surface was imprinted on to clean glass slides followed by toluidine blue and rapid Papanicolaou staining. Subsequently the lymph node slices were cut at three levels using the cryostat machine and stained with Hematoxylin and eosin stain. The cytological and FS findings were compared and the specificity, sensitivity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of TIC and FS was evaluated taking histopathological diagnosis as gold standard. In addition, pooled sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for touch imprint cytology and frozen section were assessed for the studies included in the meta-analysis. RESULTS: The specificity, sensitivity, diagnostic accuracy, positive predictive value and negative predictive value of touch imprint cytology were 100%, 88.2%, 90%, 100% and 60% respectively. The specificity, sensitivity, diagnostic accuracy, PPV and NPV of frozen section were 100%, 94.1%, 95%, 100% and 75% respectively. The sensitivity of TIC and FS for detection of micrometastasis was 60% and 80% respectively. The pooled sensitivity and specificity for touch imprint cytology were 85.24% (95% CI, 83.46%-86.90%), and 98.99% (95% CI, 98.69%-99.23%) respectively. The pooled sensitivity and specificity for frozen section examination were 90.45% (95% CI, 85.15%-94.34%), and 100% (95% CI, 99.24%-100%) respectively. CONCLUSION: Even though the sensitivity of FS was better than imprint cytology in detection of micrometastasis, TIC is a rapid inexpensive technique which can be utilized in remote areas in absence of cryostat machine. The sensitivity of the two techniques with respect to detection of macrometastasis was comparable. This meta-analysis highlights the accuracy of the touch imprint cytology and frozen section examination in the intra-operative detection of malignancy in breast cancer.


Assuntos
Neoplasias da Mama , Secções Congeladas , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela , Humanos , Secções Congeladas/métodos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela/métodos , Citodiagnóstico/métodos , Prognóstico , Metástase Linfática/patologia , Metástase Linfática/diagnóstico , Sensibilidade e Especificidade , Período Intraoperatório , Citologia
3.
Cytojournal ; 21: 4, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38343762

RESUMO

Objective: The most important determinant of patient outcome in cases of breast carcinoma is the regional lymph node status. Intraoperative assessment of sentinel lymph nodes (SLNs) allows the surgeon to perform axillary lymph node dissection in the same sitting if required. The commonly performed intraoperative methods for SLN evaluation are touch imprint cytology (TIC) and frozen section. The present study aimed to determine the sensitivity, specificity, and accuracy of TIC with histopathological diagnosis as gold standard. Material and Methods: The lymph nodes sent for intraoperative examination were bisected along the long axis and touched onto clean glass slides followed by Toluidine blue and rapid Papanicolaou staining. The imprints were reviewed and the interpretation was conveyed to the surgeon. Thereafter, the biopsy was fixed in 10% formalin followed by paraffin embedding with hematoxylin and eosin staining. The specificity, sensitivity, diagnostic accuracy, positive predictive value, and negative predictive value were evaluated with histopathological diagnosis as gold standard. Results: A total of 60 patients who underwent resection surgery were included in the study. Majority (36.7%) of patients were in the age group 41-50 years with a mean age of 48.1 ± 10.6 years. There were 54 cases (90%) and 6 cases (10%) of invasive carcinoma of no special type (ductal) and lobular carcinoma, respectively. According to modified Bloom-Richardson scoring, the cases were categorized as Grade 1-6 cases (10%), Grade 2-36 (60%), and Grade 3-18 (30%). The sensitivity and specificity of TIC were 87.5% and 100%, respectively. The diagnostic accuracy of TIC in the diagnosis of metastasis in SLN was 90%. Conclusion: TIC is an easy-to-perform, cost-effective, rapid, and accurate technique for axillary lymph node evaluation, which also overcomes the need for a cryostat.

4.
Cureus ; 15(10): e47682, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38021761

RESUMO

Ameloblastoma is one of the most prevalent but enigmatic benign odontogenic tumors of the jaw, accounting for approximately 10% of all maxillary and mandibular tumors. This neoplasia is distinguished by exhibiting several clinical and histological variants along with several mutations that affect its behavior. The ameloblastoma treatment plan is determined by the tumor's size, anatomical location, histologic variant, and anatomical involvement. On chromosome 7, there is a proto-oncogene called BRAF. When BRAF is mutated, it becomes an oncogene and continuously produces proteins like MEK and ERK, members of mitogen-activated protein kinase (MAPK). In the signaling pathway, these proteins activate transcription factor inside the nucleus that helps in cell division and growth. Numerous neoplasms have been linked to more than 40 BRAF mutations. The most common one is BRAF proto-oncogene serine/threonine kinase (BRAF) V600E, whose treatment has been linked to a positive outcome. BRAF inhibitors like vemurafenib, dabrafenib, and sorafenib have shown excellent results, especially in metastatic ameloblastoma. BRAF, particularly in the case of metastatic ameloblastoma, inhibitors such as vemurafenib, dabrafenib, and sorafenib, has demonstrated outstanding results. Targeted therapies have been employed as adjuvant therapies to enhance cosmetic outcomes, even though no reports of serial cases demonstrate their effectiveness in ameloblastomas. In the treatment of ameloblastomas, the identification of BRAF V600E and additional mutations as the prime targeted therapies has proven to be a significant breakthrough where surgical treatment was contraindicated. In this article, we review the presence of BRAF V600E mutations, their inhibitors, and targeted therapies in ameloblastoma.

5.
Drug Resist Updat ; 71: 101004, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37660590

RESUMO

ATP-binding cassette (ABC) transporters such as ABCB1, ABCG2, and ABCC1 are the major players in drug efflux-mediated multidrug resistance (MDR), which severely affects the efficacy of chemotherapy. Several synthetic compounds block the drug transport by ABC transporters; however, they exhibit a narrow therapeutic window, and produce side effects in non-target normal tissues. Conversely, the downregulation of the expression of ABC drug transporters seems to be a promising strategy to reverse MDR in cancer cells. Several signaling pathways, such as NF-κB, STAT3, Gli, NICD, YAP/TAZ, and Nrf2 upregulate the expression of ABC drug transporters in drug-resistant cancers. Recently, natural medicinal compounds have gained importance to overcome the ABC drug-efflux pump-mediated MDR in cancer. These compounds target transcription factors and the associated signal transduction pathways, thereby downregulating the expression of ABC transporters in drug-resistant cancer cells. Several potent natural compounds have been identified as lead candidates to synergistically enhance chemotherapeutic efficacy, and a few of them are already in clinical trials. Therefore, modulation of signal transduction pathways using natural medicinal compounds for the reversal of ABC drug transporter-mediated MDR in cancer is a novel approach for improving the efficiency of the existing chemotherapeutics. In this review, we discuss the modulatory role of natural medicinal compounds on cellular signaling pathways that regulate the expression of ABC transporters in drug-resistant cancer cells.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Neoplasias , Humanos , Transportadores de Cassetes de Ligação de ATP/genética , NF-kappa B , Neoplasias/tratamento farmacológico , Neoplasias/genética , Resistência a Múltiplos Medicamentos , Transdução de Sinais
6.
Indian Dermatol Online J ; 14(3): 388-390, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37266080

RESUMO

Leprosy is a chronic infectious granulomatous disease caused by Mycobacterium leprae, primarily affecting the skin and the peripheral nerves. Variable involvement of internal organs and mucosa has been reported with incidence ranging from 19% to 60%, more commonly seen in lepromatous spectrum of leprosy (LL and BL). We report a case of borderline tuberculoid (BT) leprosy presenting with oral mucosal lesions involving the gingival mucosa and lower lip.

7.
Plant Sci ; 334: 111736, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37211221

RESUMO

The tomato is well-known for its anti-oxidative and anti-cancer properties, and with a wide range of health benefits is an important cash crop for human well-being. However, environmental stresses (especially abiotic) are having a deleterious effect on plant growth and productivity, including tomato. In this review, authors describe how salinity stress imposes risk consequences on growth and developmental processes of tomato through toxicity by ethylene (ET) and cyanide (HCN), and ionic, oxidative, and osmotic stresses. Recent research has clarified how salinity stress induced-ACS and - ß-CAS expressions stimulate the accumulation of ET and HCN, wherein the action of salicylic acid (SA),compatible solutes (CSs), polyamines (PAs) and ET inhibitors (ETIs) regulate ET and HCN metabolism. Here we emphasize how ET, SA and PA cooperates with mitochondrial alternating oxidase (AOX), salt overly sensitive (SOS) pathways and the antioxidants (ANTOX) system to better understand the salinity stress resistance mechanism. The current literature evaluated in this paper provides an overview of salinity stress resistance mechanism involving synchronized routes of ET metabolism by SA and PAs, connecting regulated network of central physiological processes governing through the action of AOX, ß-CAS, SOS and ANTOX pathways, which might be crucial for the development of tomato.


Assuntos
Etilenos , Estresse Salino , Solanum lycopersicum , Etilenos/metabolismo , Solanum lycopersicum/metabolismo , Solanum lycopersicum/fisiologia , Estresse Salino/fisiologia
8.
Int J Pharm ; 635: 122763, 2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-36822336

RESUMO

In this study, we prepared a ß-cyclodextrin polymer (ß-CDP) co-loaded quercetin (QCT) and doxorubicin (DOX) nanocarrier (ß-CDP/QD NCs) by freeze-dried method to combat P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in KB-ChR 8-5 cancer cells. Various microscopic and spectroscopic techniques were employed to characterize the prepared nanocarrier. The molecular docking studies confirm the effective binding interactions of QCT and DOX with the synthesized ß-CD polymer. The in vitro drug release study illustrates the sustainable release of DOX and QCT from the ß-CDP nanocarrier. Further, we noticed that the QCT released from the ß-CDP nanocarrier improved the intracellular availability of DOX via modulating P-gp drug efflux function in KB-ChR 8-5 cells and MCF-7/DOX cancer cells. Cell uptake results confirmed the successful internalization of DOX in KB-ChR 8-5 cells compared with free DOX. Cell-based assays such as nuclear condensation, alteration in the mitochondrial membrane potential (MMP), and apoptosis morphological changes confirmed the enhanced anticancer effect of ß-CDP/QD NCs in the resistant cancer cells. Hence, QCT and DOX co-loaded ß-CDP may be considered effective in achieving maximum cell death in the P-gp overexpressing MDR cancer cells.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Antineoplásicos , Humanos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Quercetina/farmacologia , Polímeros/farmacologia , Simulação de Acoplamento Molecular , Resistencia a Medicamentos Antineoplásicos , Doxorrubicina/farmacologia , Doxorrubicina/química , Resistência a Múltiplos Medicamentos , Subfamília B de Transportador de Cassetes de Ligação de ATP , Células MCF-7 , Linhagem Celular Tumoral
9.
J Nanobiotechnology ; 20(1): 423, 2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36153528

RESUMO

Cancer often develops multidrug resistance (MDR) when cancer cells become resistant to numerous structurally and functionally different chemotherapeutic agents. MDR is considered one of the principal reasons for the failure of many forms of clinical chemotherapy. Several factors are involved in the development of MDR including increased expression of efflux transporters, the tumor microenvironment, changes in molecular targets and the activity of cancer stem cells. Recently, researchers have designed and developed a number of small molecule inhibitors and derivatives of natural compounds to overcome various mechanisms of clinical MDR. Unfortunately, most of the chemosensitizing approaches have failed in clinical trials due to non-specific interactions and adverse side effects at pharmacologically effective concentrations. Nanomedicine approaches provide an efficient drug delivery platform to overcome the limitations of conventional chemotherapy and improve therapeutic effectiveness. Multifunctional nanomaterials have been found to facilitate drug delivery by improving bioavailability and pharmacokinetics, enhancing the therapeutic efficacy of chemotherapeutic drugs to overcome MDR. In this review article, we discuss the major factors contributing to MDR and the limitations of existing chemotherapy- and nanocarrier-based drug delivery systems to overcome clinical MDR mechanisms. We critically review recent nanotechnology-based approaches to combat tumor heterogeneity, drug efflux mechanisms, DNA repair and apoptotic machineries to overcome clinical MDR. Recent successful therapies of this nature include liposomal nanoformulations, cRGDY-PEG-Cy5.5-Carbon dots and Cds/ZnS core-shell quantum dots that have been employed for the effective treatment of various cancer sub-types including small cell lung, head and neck and breast cancers.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carbono/farmacologia , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Nanotecnologia , Neoplasias/metabolismo , Microambiente Tumoral
10.
PLoS One ; 15(3): e0230282, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160243

RESUMO

Cloning and expression of a desired gene is indispensable in molecular biology studies. Expression vectors, in this regard, should offer much needed flexibility and choice of cloning strategies for both in vivo and in vitro protein expression experiments. Furthermore, availability of option to choose from various reporter tags allows one to be flexible during designing of an experiment in a more relevant manner. Thus, the need of a versatile expression system cannot be ignored. Although several different expression vectors are available for gene expression in mycobacteria, they lack the required versatility of expression and the inclusion of reporter tags. We here present the construction of a set of nine E. coli-Mycobacterium shuttle plasmids, which offer a combination of three mycobacterial promoter systems (heat shock inducible-hsp60, tetracycline-, and acetamide-inducible) along with three polypeptide tags (Green Fluorescent Protein (GFP), Glutathione S-transferase (GST) and hexa-histidine tag). These vectors offer the cloning of a target gene in all the nine given vectors in parallel, thus allowing the generation of recombinant plasmids that will express the target gene from different promoters with different tags. Here, while the hexa-histidine and GST tags can be used for protein purification and pull-down experiments, the GFP-tag can be used for protein localization within the cell. Additionally, the vectors also offer the choice of positioning of the reporter tag either at the N-terminus or at the C-terminus of the expressed protein, which is achieved by cloning of the gene at any of the two blunt-end restriction enzyme sites available in the vector. We believe that these plasmids will be extremely useful in the gene expression studies in mycobacteria by offering the choices of promoters and reporters. Our work also paves the way to developing more such plasmids with other tags and promoters that may find use in mycobacterial biology.


Assuntos
Engenharia Genética/métodos , Vetores Genéticos/genética , Mycobacterium/genética , Escherichia coli/genética , Genes Reporter , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Histidina/genética , Histidina/metabolismo , Oligopeptídeos/genética , Oligopeptídeos/metabolismo , Regiões Promotoras Genéticas , Ativação Transcricional
11.
J Orthod ; 46(4): 358-366, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31597525

RESUMO

INTRODUCTION: Ectopic eruption, manifesting as an aberration in the normal path of eruption of a tooth, can adversely impact facial aesthetics, phonetics and psychosocial development. DESCRIPTION: This case series describes the orthodontic management of two adolescent patients with different clinical presentations of ectopically erupted maxillary central incisors secondary to trauma during the primary dentition period. The therapy primarily included periodontal soft-tissue surgery accompanied by orthodontic traction to align the ectopic incisors. Frenectomy was performed in one patient and surgical excision of a hypertrophied pseudo-pouch in the second patient. A modified maxillary lip bumper was used concomitantly for management of associated soft-tissue trauma, thus facilitating healing and aiding orthodontic traction. RESULTS: Appropriately planned interdisciplinary management involving the interim use of a modified lip bumper allowed proper alignment of the ectopically positioned incisors with a stable outcome at three-year follow-up. CONCLUSION: Fixed orthodontic therapy with concurrent use of modified maxillary lip bumper is an effective approach to treat incisors erupted ectopically in relation to the upper lip and frenum.


Assuntos
Incisivo , Lábio , Adolescente , Humanos , Maxila
12.
Chem Sci ; 10(24): 6184-6192, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31360425

RESUMO

Robust inorganic graphene analogues with atomic level sharp edges have seldom been investigated to decipher the interaction of two-dimensional materials with the cell membrane. Silica nanosheets (NSs) with four different thicknesses between 2.9 nm and 11.1 nm were synthesized by microwave irradiation and these colloidal NSs were able to spontaneously penetrate the cell membrane leaving membrane perforations at their sites of entry. The NS-ingression was most effective with the thinnest NSs, when studied in vitro. The atomistic details of the NS-membrane interaction were revealed by molecular dynamics (MD) simulations, which showed that the extraction of phospholipids was most favored when NSs were oriented vertically with respect to the membrane surface. While the folic acid modified NSs demonstrated a riveting tendency to penetrate the cancer cell membrane, co-modification with doxorubicin (DOX) unexpectedly reduced their capability. Migrating away from a conventional drug delivery approach, here we show that silica NSs can kill cancer cells primarily by mechanical scalpelling. Targeted ingress could be achieved through antibody conjugation on the NSs and thus only cancerous HeLa cells are affected by this treatment, leaving the normal HEK-293 cells intact. This destructive ingress through limited oxidative stress offers a previously unexplored route to treat fatal diseases without the necessity of transporting expensive drugs or radiation therapy, thereby bypassing deleterious side effects on healthy cells.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32010634

RESUMO

Trichomonas vaginalis is the parasitic protozoan residing in human urogenital tract causing trichomoniasis, which is the leading non-viral sexually transmitted disease. It has cosmopolitan distribution throughout the globe and affects both men and women. Lifecycle of the parasite has been traditionally described as consisting of motile and symptom-causing trophozoites. Chemical and temperature perturbations in trophozoites have been shown to aid conversion to pseudocysts, which is poorly investigated. In the current study, we show the formation of viable cyst-like structures (CLS) in stationary phase of T. vaginalis axenic culture. We used a fluorescent stain called calcofluor white, which specifically binds to chitin and cellulose-containing structures, to score for T. vaginalis CLS. Using flow cytometry, we demonstrated and quantitated the processes of encystation as well as excystation; thus, completing the parasite's lifecycle in vitro without any chemical/temperature alterations. Like cysts from other protozoan parasites such as Entamoeba histolytica and Giardia lamblia, T. vaginalis CLS appeared spherical, immotile, and resistant to osmotic lysis and detergent treatments. Ultrastructure of CLS demonstrated by Transmission Electron Microscopy showed a thick electron-dense deposition along its outer membrane. To probe the physiological role of CLS, we exposed parasites to vaginal pH and observed that trophozoites took this as a cue to convert to CLS. Further, upon co- culturing with cells of cervical origin, CLS rapidly excysted to form trophozoites which abrogated the cervical cell monolayer in a dose-dependent manner. To further corroborate the presence of two distinct forms in T. vaginalis, we performed two-dimensional gel electrophoresis and global, untargeted mass spectrometry to highlight differences in the proteome with trophozoites. Interestingly, CLS remained viable in chlorinated swimming pool water implicating the possibility of its role as environmentally resistant structures involved in non-sexual mode of parasite transmission. Finally, we showed that symptomatic human patient vaginal swabs had both T. vaginalis trophozoites and CLS; thus, highlighting its importance in clinical infections. Overall, our study highlights the plasticity of the pathogen and its rapid adaption when subjected to stressful environmental cues and suggests an important role of CLS in the parasite's life cycle, pathogenesis and transmission.


Assuntos
Cistos/parasitologia , Cistos/ultraestrutura , Estágios do Ciclo de Vida , Trichomonas vaginalis/fisiologia , Trichomonas vaginalis/ultraestrutura , Plasticidade Celular , Entamoeba histolytica/metabolismo , Feminino , Giardia lamblia/metabolismo , Células HeLa , Humanos , Microscopia Eletrônica de Transmissão , Encistamento de Parasitas/fisiologia , Proteoma/análise , Proteômica , Proteínas de Protozoários/metabolismo , Estresse Fisiológico , Trofozoítos/metabolismo , Trofozoítos/ultraestrutura , Vagina/parasitologia
14.
Pharm Pat Anal ; 7(4): 155-167, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29882724

RESUMO

Celastrol is a highly investigated anticancer moiety. It is a pentacyclic triterpenoid, isolated several decades ago with promising role in chemoprevention. Celastrol has been found to target multiple proinflammatory, angiogenic and metastatic proteins. Inhibition of these targets results in significant reduction of cancer growth, survival and metastasis. This review summarizes the varied molecular targets of celastrol along with insight into the various recently published clinical, preclinical and industrial patents (2011-2017).


Assuntos
Antineoplásicos , Patentes como Assunto , Triterpenos , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Triterpenos Pentacíclicos , Triterpenos/química , Triterpenos/farmacologia , Triterpenos/uso terapêutico
15.
Carbohydr Polym ; 182: 188-198, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29279114

RESUMO

Computational analyses followed by traditional wet-bench experiments have become a method of choice due to successful results. To enhance the solubility and bioavailability of curcumin within chitosan nanoparticle, we have exploited computational methodologies i.e. docking, BBD-RSM and MD simulation for the polymer selection, NPs' formulation, optimization and their stability confirmation in an aqueous medium, respectively. Formulated CSCur NPs were assessed for in-vitro release, which exhibited a sustained release pattern and four-fold higher cytotoxic activity in a nanoparticulated system. Enhanced uptake, apoptotic effect of CSCur NPs were established by morphological changes in cells as observed by fluorescence microscopy and FE-SEM. DNA damage, cell-cycle blockage and elevated ROS levels further confirm the anticancer activity of the CSCur NPs following apoptotic pathways. In-vivo study on Danio rerio, for uptake and toxicity reveal the particle's biocompatibility and nontoxicity. Therefore, CSCur NPs could be the potential formulation for a safe chemotherapeutic drug for cancer.


Assuntos
Antineoplásicos/farmacologia , Quitosana/química , Curcumina/química , Curcumina/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Nanopartículas/química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Relação Estrutura-Atividade
16.
J Biomol Struct Dyn ; 36(9): 2203-2215, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28672114

RESUMO

Polyproline II (PPII) fold, a peculiar structural element was detected in the Amaranthus caudatus seed lectin (ACL) based on far UV circular dichroism spectrum, conformational transitions of the lectin, and a distinct isodichroic point in thermal denaturation. It was confirmed using PolyprOnline database to estimate the percentage of amino acids contributing to PPII fold and showed the values as 13.5 and 13.9% for PROSS and XTLSSTR, respectively. Investigations of the functional and conformational transitions of ACL during thermal-, pH-, and guanidine hydrochloride (GdnHCl)-induced denaturation were carried out using biochemical and biophysical techniques and molecular dynamics (MD) simulations approach. The lectin got aggregated at 60°C with instantaneous structural alterations. The aggregation-prone regions in ACL were predicted using online servers viz. AGGRESCAN, AmylPred, FoldAmyloid, and Waltz that were represented by Visual Molecular Dynamics tools. Nine conserved regions were identified by these softwares as being 'hot-spots' for aggregation. MD simulation studies of the lectin at 60°C revealed increase in radius of gyration. The loss of PPII fold in 2.0 M GdnHCl was reversible. The partially unfolded intermediate of ACL with diminished PPII fold formed at pH 1.0 was stable up to 90°C. The polyproline II fold has been rarely detected in lectins, ACL being the second after the potato lectin.


Assuntos
Lectinas/química , Simulação de Dinâmica Molecular , Peptídeos/química , Dobramento de Proteína , Aminoácidos , Hemaglutinação , Testes de Hemaglutinação , Concentração de Íons de Hidrogênio , Conformação Molecular , Agregados Proteicos , Desnaturação Proteica , Relação Quantitativa Estrutura-Atividade , Análise Espectral , Temperatura
17.
J Contemp Dent Pract ; 18(2): 100-106, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28174361

RESUMO

INTRODUCTION: The most commonly impacted tooth in the oral cavity is the mandibular third molar. Various etiologic factors have been suggested for impacted mandibular third molars. The pattern and prevalence of impacted mandibular third molars vary with different population and region. This study throws light on the prevalence and pattern of impacted mandibular third molars in Eritrea, East Africa. This is the first reported study regarding the same from Eritrea. AIM: To assess the prevalence and pattern of impacted mandibu-lar third molars in the population of Eritrea, East Africa by conducting a retrospective study from January 2009 to January 2014. MATERIALS AND METHODS: This study was conducted in the Department of Oral and Maxillofacial Surgery, Orotta School of Medicine and Dental Medicine and the Orotta Referral Medical and Surgical Hospital, Asmara, Eritrea. A total of 1,813 clinical and radiographic records [orthopantomograms] were assessed and 276 cases were selected for the study as per the inclusion criteria. They were evaluated for the frequency among the various age groups, gender and region along with the sides affected, angulation and level of impaction. The presence of systemic conditions and associated pathologies was also assessed according to the type of impaction. RESULTS: The average age of these patients in the study was found to be 30 years, with the 20 to 30 years age group being the most affected (67.4%). Females (53.3%) were affected more than the males (46.7%). People from the Asmara region showed significantly more prevalence (79.7%) than the adjoining areas (20.3%). Mesioangular impaction was the most common angulation with a definite relationship to the age groups (p = 0.032). The level of impaction had no significant relationship to the age groups, gender, or region, although class I position A was found to be the most common type. Mesioangular class I position A impac-tion showed an apparent relationship with underlying systemic conditions, but it was statistically insignificant. Mesioangular impaction was found to be associated with the most number of pathologies (p = 0.001). CONCLUSION: The prevalence of mandibular impaction was less in Eritrea (15.2%) compared with other populations. This study provides useful baseline data for the prevalence and pattern of mandibular impaction in the Eritrean population. CLINICAL SIGNIFICANCE: This study throws light on the pattern, type, and frequency of mandibular impacted teeth as per age, sex, and region among the population of Eritrea.


Assuntos
Mandíbula/diagnóstico por imagem , Dente Serotino/diagnóstico por imagem , Dente Impactado/diagnóstico por imagem , Dente Impactado/epidemiologia , Adulto , Fatores Etários , Eritreia/epidemiologia , Feminino , Humanos , Masculino , Mandíbula/patologia , Dente Serotino/patologia , Prevalência , Radiografia Panorâmica/métodos , Estudos Retrospectivos , Fatores Sexuais , Dente Impactado/patologia
18.
Int J Biol Macromol ; 91: 75-84, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27185070

RESUMO

Functional and conformational transitions of the Sophora japonica seed lectin (SJL) were studied in detail using bioinformatics and biophysical tools. Homology model of the lectin displayed all the characteristics of the legume lectin monomer and the experimental observations correlated well with the structural information. In silico studies were performed by protein-ligand docking, calculating the respective binding energies and the residues involved in the interactions were derived from LigPlot(+) analysis. Fluorescence titrations showed three times higher affinity of T-antigen disaccharide than N-acetyl galactosamine (GalNAc) towards SJL indicating extended sugar binding site of the lectin. Thermodynamic parameters of T-antigen binding to SJL indicated the process to be endothermic and entropically driven while those of GalNAc showed biphasic process. SDS-PAGE showed post-translationally modified homotetrameric species of the lectin under native conditions. In presence of guanidine hydrochloride (0.5-5.0M), the tetramer first dissociated into dimers followed by unfolding of the protein as indicated by size exclusion chromatography, fluorescence and CD spectroscopy. Different structural rearrangements were observed during thermal denaturation of SJL at physiological pH 7.2, native pH 8.5 and molten globule inducing pH 1.0. Topological information revealed by solute quenching studies at respective pH indicated differential hydrophobic environment and charge density around tryptophan residues.


Assuntos
Metabolismo dos Carboidratos , Lectinas de Plantas/química , Lectinas de Plantas/metabolismo , Acetilgalactosamina/metabolismo , Antígenos Virais de Tumores/metabolismo , Concentração de Íons de Hidrogênio , Simulação de Acoplamento Molecular , Ligação Proteica , Desnaturação Proteica , Estrutura Quaternária de Proteína , Relação Estrutura-Atividade , Temperatura
19.
J Ir Dent Assoc ; 58(2): 95-100, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22611790

RESUMO

Radicular lingual grooves are morphological defects, which are found most frequently in maxillary anterior teeth and are a predisposing factor for periodontal disease. They are easily overlooked as aetiologic factors, as these grooves are covered by periodontal tissues. This case report presents a successful management of a case of a maxillary lateral incisor with an associated radicular lingual groove and severe periapical osseous destruction in a 30-year-old female patient. A combination of endodontic treatment, radiculoplasty to eliminate the radicular lingual groove, and periapical surgery to eliminate the periapical osseous defect was used. At two-year follow-up, the patient was comfortable and complete resolution of the periapical pathology was evident.


Assuntos
Incisivo/anormalidades , Periodontite Periapical/terapia , Anormalidades Dentárias/cirurgia , Ápice Dentário/cirurgia , Raiz Dentária/anormalidades , Adulto , Perda do Osso Alveolar/cirurgia , Regeneração Óssea , Transplante Ósseo , Fístula Dentária/cirurgia , Feminino , Humanos , Maxila , Periodontite Periapical/etiologia , Periodontite Periapical/cirurgia , Tratamento do Canal Radicular , Anormalidades Dentárias/complicações
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