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A self-assembly-directed thixotropic metallohydrogel (i.e., Mg-Tetrakis) of Mg(II)-metal salt and N,N,N',N'-tetrakis(2-hydroxy-ethyl)ethylenediamine (i.e., Tetrakis) was successfully achieved. The organic chemical component N,N,N',N'-tetrakis(2-hydroxy-ethyl)ethylenediamine was used as a low-molecular-weight gelator, and water was employed as the gel-forming solvent. The fabricated supramolecular metallohydrogel promisingly depicted viscoelastic and mechanoelastic behaviors, which are interpreted through various rheological parameters. The thixotropic behavior of the metallohydrogel is also well characterized through this rheological study. Field emission scanning electron microscopy microstructural analyses were performed to visualize the morphological arrangements of the metallohydrogel. The anticancer properties of the synthesized metallogels are investigated through this work. The cytotoxic potential of the metallohydrogel on the MCF-7 breast cancer cell line is critically examined. Reducing the growth of breast cancer cell line MCF-7 through the treatment of gel on the colony formation assay has been explored through the work. The antimigratory potential of the metallohydrogel on the MCF-7 cell was also scrutinized. The anticancer effect of the fabricated metallohydrogel is inspected through various assay formation strategies, like wound healing assay, tumor spheroid inhibition assay, nuclear fragmentation assay, and so on. Quantitative reactive oxygen species analysis of the cancer cells by treatment with the metallohydrogel was also conducted through this study. The mechanistic apoptosis study was executed by studying the expression of various apoptotic markers like BAX, BCL2, PUMA, and NOXA.
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Uncontrolled proliferation and altered metabolism of cancer cells result in an imbalance of nutrients and oxygen supply, and persuade hypoxia. Hypoxia, in turn, activates the transcription gene HIF-1α, which eventually upregulates the efflux transporter P-gp and induces multidrug resistance (MDR). Thus, hypoxia leads to the development of resistance to conventional therapies. Therefore, the fabrication of a nanoscale porous system enriched with upconversion nanoparticles to target cancer cells, evade hypoxia, and enhance anticancer therapy is the key goal of this article. Herein, upconversion nanoparticles are embedded in a nanoscale porous organic polymer (POP) and further conjugated with a targeting moiety and a catalase molecule. The nanoscale POP embedded in UCNPs is generated at room temperature. The targeting ligand, lactobionic acid, is attached after polymer coating, which effectively targets liver cancer cells. Then, catalase is grafted effectively to produce oxygen. Endogenously generated oxygen alleviates hypoxia in liver cancer cells. The drug- and catalase-loaded composite exhibit greater cytotoxicity in hypoxic liver cells than in normal cells by overcoming hypoxia and downregulating the hypoxia-inducible factors.
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ETHNOPHARMACOLOGICAL RELEVANCE: Ruellia tuberosa L. (Acanthaceae) is a weed plant traditionally used in folklore medicine as a diuretic, anti-hypertensive, anti-pyretic, anti-cancerous, anti-diabetic, analgesic, and gastroprotective agent. It has been previously reported that R. tuberosa L. is enriched with various flavonoids, exhibiting significant cytotoxic potential in various cancer models but a detailed study concerning its molecular mechanism is yet to be explored. AIM OF THE STUDY: Exploring and validating R. tuberosa L. flower methanolic extract (RTME) as an anti-cancerous agent as per traditional usage with special emphasis on multi-drug resistant human triple-negative breast cancer (TNBC) and investigating the possible signaling networks and regulatory pathways involved in it. MATERIALS AND METHODS: In this study, RTME was prepared using methanol, and phytochemical analysis was performed through GC-MS. Then, the extract was tested for its anti-cancer potential through in-vitro cytotoxicity assay, clonogenic assay, wound healing assay, ROS generation assay, cell cycle arrest, apoptotic nuclear morphology study, cellular apoptosis study, mitochondrial membrane potential (MMP) alteration study, protein, and gene expressions alteration study. In addition, toxicological status was evaluated in female Balb/C mice, and to check the receptor-ligand interactions, in-silico molecular docking was also conducted. RESULTS: Several phytochemicals were found within RTME through GC-MS, which have been already reported to act as ROS inductive, DNA damaging, cell cycle arresting, and apoptotic agents against cancer cells. Moreover, RTME was found to exhibit significant in-vitro cytotoxicity along with a reduction in colony formation, and inhibition of cell migratory potential. It also induced intracellular ROS, promoted G0/G1 cell cycle arrest, caused mitochondrial membrane potential (MMP) alteration, and promoted cell death. The Western blot and qRT-PCR data revealed that RTME promoted the intrinsic pathway of apoptosis. Furthermore, blood parameters and organ histology on female Balb/C mice disclosed the non-toxic nature of RTME. Finally, an in-silico molecular docking study displayed that the three identified lead phytochemicals in RTME show strong receptor-ligand interactions with the anti-apoptotic Bcl-2 and give a clue to the possible molecular mechanism of the RTME extract. CONCLUSIONS: RTME is a potential source of several phytochemicals that have promising therapeutic potential against TNBC cells, and thus could further be utilized for anti-cancer drug development.
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Acanthaceae , Antineoplásicos Fitogénicos , Apoptosis , Daño del ADN , Flores , Extractos Vegetales , Especies Reactivas de Oxígeno , Neoplasias de la Mama Triple Negativas , Apoptosis/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Humanos , Daño del ADN/efectos de los fármacos , Línea Celular Tumoral , Animales , Femenino , Flores/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Acanthaceae/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Simulación del Acoplamiento Molecular , Ratones Endogámicos BALB CRESUMEN
Preoperative chemoradiotherapy is a standard treatment for patients with locally advanced, resectable esophageal cancer. The treatment completion rates impact the survival outcomes (Eyck et al J Clin Oncol 39(18):1995-2004, 2021). Thus, we aimed to estimate the effect of neoadjuvant chemoradiotherapy (NACRT) in terms of treatment completion rates and survival in this subset of patients and bring out the clinical outcomes in that context. This was a retrospective study done at a tertiary cancer center in North-East India. The study period was from 1 January 2018 to 31 December 2021. We included patients diagnosed with locally advanced and resectable esophageal cancer (cT2-3NanyM0) involving the middle and/or lower thoracic esophagus and who were planned for trimodality treatment in the Joint Tumor Board. Out of the 82 patients who were planned for trimodality treatment, all were squamous cell carcinomas. We found that 54.9% of patients completed the entire trimodality treatment. The median age was 56 years (range 34 to 73 years). The male to female ratio was 59:23. Adverse events, of any grade, were seen in 76% of patients who received NACRT. Fatigue (66%) was the most common toxicity. The common hematologic toxicities were neutropenia and anemia (7.3% each). A total of 45 patients (54.9%) were able to complete all the three modalities of treatment. Transthoracic esophagectomy was the preferred approach (84.4%). The site of anastomosis was in the neck of all the patients. Anastomotic leak was seen in 17.7% of patients. Postoperative pulmonary and cardiac complications occurred in 31.1% and 8.9% of patients respectively. The 30-day mortality was 6.7% (three deaths). A pathological complete response was seen in 35.6% among patients who underwent an esophagectomy. R0 resection was achieved in 93.3% of patients. The median overall survival and disease-free survival were 19 months and 17 months respectively. The completion rate of trimodality treatment in the real-world scenario was found to be low in our study, the reasons for which need to be identified and effectively resolved. Oncological outcomes were similar to the published literature.
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Forequarter amputation (interscapulothoracic amputation) includes surgical removal of an upper limb and the shoulder girdle, including the scapula and a portion of the clavicle. We aim to report about our recent experience of having to resort to this mutilating surgery and the clinicopathological variables in that context. The study was done at a cancer centre in Northeast India. It was an ambispective study design, where the patient cohort who underwent FQA was identified retrospectively from the operative register of major surgeries for the time period 1st June 2020 to 31st May 2022 (24 months), and these patients were followed up prospectively from 1st June 2022 to 31st May 2023 (1 year). The study variables were obtained from the electronic medical records (EMR), the physical case files and the hospital-based cancer registry (HBCR). There were 7 patients who underwent forequarter amputation (FQA) during the two years, and in the same period, 15 patients underwent limb salvage surgery for tumours around the shoulder girdle. This translates to a FQA rate of 31.8%. The male:female ratio of the patients was 3:4. The median age of the patients was 32 years (range 19 to 59 years). The histologies included osteosarcoma (2), chondrosarcoma (2), Ewing's sarcoma (2) and hidradenocarcinoma (1). None of these patients had any distant metastatic disease. Four patients had local disease progression on neoadjuvant chemotherapy. Three of the patients had emergency surgery as a life-saving procedure on account of bleeding from their ulcerated tumours. Two patients had disease which was recurrent and unsalvageable due to the encasement of the neurovascular bundle. The median follow-up was 8 months (range 4 to 18 months). Five patients had distant recurrence with pulmonary metastases (100%) and bone secondaries (14.3%) within a range of 3 to 8 months. None of the patients had any local recurrence. Two patients are on follow-up without any evidence of disease (17 and 18 months respectively). Forequarter amputation is the surgical option when tumours around the shoulder girdle are not amenable to limb-sparing procedures by virtue of their disease extent. These cancers are usually aggressive leading to early distant metastasis.
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Malignant tumor cells go through morphological and gene expression alterations, including rearrangement of cytoskeleton proteins that promote invasion and metastasis. Microtubules form a major cytoskeleton component that plays a significant role in regulating multiple cellular activities and function depending on the presence of posttranslational modification (PTM). Acetylation is a type of PTM that generally occurs in the lysine 40 region of α-tubulin and is known to be critically associated with cancer metastasis. Current evidence demonstrates that noncoding RNAs, such as long noncoding RNA (lncRNA) and microRNA (or miRNA), which are correlated with gene regulation modulate the expression of acetylated tubulin in the development and metastasis of cancer. This review provides an overview about the role of lncRNA and miRNA in regulation of tubulin acetylation in various types of cancer.
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MicroARNs , Neoplasias , ARN Largo no Codificante , Humanos , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Acetilación , Microtúbulos/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Procesamiento Proteico-PostraduccionalRESUMEN
BACKGROUND: Population-based cancer survival is a key indicator for assessing the effectiveness of cancer control by a health care system in a specific geographic area. Breast cancer is the most common cancer among women in India, accounting for over one quarter of all female cancers. The objective of this study was to estimate the 5-year survival of female patients who were diagnosed with breast cancer between 2012 and 2015 from the existing Population-Based Cancer Registries (PBCRs) in India. METHODS: In total, 17,331 patients who had breast cancer diagnosed between 2012 and 2015 from 11 PBCRs were followed until June 30, 2021. Active methods were used to track the vital status of registered breast cancer cases. The study conducted survival analysis by calculating the difference between the date of first diagnosis and the date of death or censoring to estimate observed survival and relative survival using the actuarial survival approach and the Ederer-II approach, respectively. RESULTS: The 5-year age-standardized relative survival (95% confidence interval [CI]) of patients with breast cancer was 66.4% (95% CI, 65.5%-67.3%). Mizoram (74.9%; 95% CI, 68.1%-80.8%), Ahmedabad urban (72.7%; 95% CI, 70.3%-74.9%), Kollam (71.5%; 95% CI, 69.2%-73.6%), and Thiruvananthapuram (69.1%; 95% CI, 67.0%-71.2%) had higher survival rates than the national average. Conversely, Pasighat had the lowest survival rate (41.9%; 95% CI, 14.7%-68.6%). The 5-year observed survival rates for localized, regional, and distant metastasis in the pooled PBCRs were 81.0%, 65.5%, and 18.3%, respectively. CONCLUSIONS: The overall disparity in survival rates was observed across 11 PBCRs, with lower survival rates reported in Manipur, Tripura, and Pasighat. Therefore, it is imperative to implement comprehensive cancer control strategies widely throughout the country.
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Neoplasias de la Mama , Sistema de Registros , Humanos , Femenino , India/epidemiología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Persona de Mediana Edad , Anciano , Adulto , Análisis de Supervivencia , Tasa de Supervivencia , Anciano de 80 o más AñosRESUMEN
Triple-negative breast cancer (TNBC) is the most elusive subtype of breast cancer that encounters treatment dilemmas owing to the paucity of druggable targets. We found hyperactivation of c-MET and ephrin type-A receptor 2 (EphA2) in patients treated with 5FU driven chemotherapy which correlated with lower disease-free survival. However, silencing of both these genes resulted in a marked decrease in the invasive, migratory, and tumorigenic potential of TNBC cells, indicating that a dual target strategy is actionable. Lupeol is a phytochemical, with potent anticancer efficacy and minimal side effects in preclinical studies. A synergistic strategy with 5FU and Lupeol elicited promising anticancer responses in vitro, in vivo, and in patient-derived ex vivo tumor culture models. This synergistic regimen is effective, even in the presence of HGF, which mechanistically orchestrates the activation of c-MET and EphA2. These data lay the foundation for the clinical validation of this combination therapy for TNBC patients.
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Platinum-based chemotherapeutic drugs are effective in killing malignant cells but often trigger drug resistance or off-target side effects. Unlike platinum, zinc is used as an endogenous cofactor for several cellular enzymes and may, thus, display increased biocompatibility. In this present study, we have rationally designed and synthesized two substituted phenanthro[9,10-d]imidazole-based ligands L1 and L2 with pyridine and quinoline substitution at the 2 position and their corresponding Zn(II) complexes; (L1)2Zn and (L2)2Zn, which are characterized by standard analytical and spectroscopic methods. (L2)2Zn, but not (L1)2Zn has intrinsic fluorescence, indicating its potential utility in imaging applications. To facilitate cellular uptake, we generated liposomal formations with a phospholipid DMPC (1,2-Dimyristoyl-sn-glycero-3-phosphocholine) through molecular self-assembly. These liposomal formulations Lip-(L1)2Zn and Lip-(L2)2Zn were able to enter breast cancer cells, induce DNA fragmentation, arrest the cell cycle at the G0/G1 phase, decrease proliferation, and promote apoptosis by activating the DNA damage response. Importantly, both Lip-(L1)2Zn and Lip-(L2)2Zn decreased the size of breast cancer cell-based spheroids, indicating they may be capable of suppressing tumor growth. Our work represents an important proof-of-concept exercise demonstrating that successful liposomal formation of phenanthro[9,10-d]imidazole-based Zn(II) complexes with inherent optical properties have great promise for the development of imaging probes and efficient anticancer drugs.
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Antineoplásicos , Neoplasias de la Mama , Humanos , Femenino , Liposomas/química , Zinc/química , Neoplasias de la Mama/tratamiento farmacológico , Apoptosis , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Imidazoles/farmacología , Proliferación CelularRESUMEN
A manganese(III) complex, [MnIII(L)(SCN)(enH)](NO3)·H2O (1â¢H2O) (H2L = 2-((E)-(2-((E)-2-hydroxy-3-methoxybenzylidene-amino)-ethyl-imino)methyl)-6-methoxyphenol), has been synthesized and characterized by single-crystal X-ray diffraction analysis. The interaction of 1â¢H2O with DNA was studied by monitoring the decrease in absorbance of the complex at λ = 324 nm with the increase in DNA concentration, providing an opportunity to determine the binding constant of the 1â¢H2O-ct-DNA complex as 5.63 × 103 M-1. Similarly, fluorescence titration was carried out by adding ct-DNA gradually and monitoring the increase in emission intensity at 453 nm on excitation at λex = 324 nm. A linear form of the Benesi-Hildebrand equation yields a binding constant of 4.40 × 103 M-1 at 25 °C, establishing the self-consistency of our results obtained from absorption and fluorescence titrations. The competitive displacement reactions of dyes like ethidium bromide, Hoechst, and DAPI (4',6-diamidine-2'-phenylindole dihydrochloride) from dye-ct-DNA conjugates by 1â¢H2O were analyzed, and the corresponding KSV values are 1.05 × 104, 1.25 × 104, and 1.35 × 104 M-1 and the Kapp values are 2.16 × 103, 8.34 × 103, and 9.0 × 103 M-1, from which it is difficult to infer the preference of groove binding over intercalation by these DNA trackers. However, the molecular docking experiments and viscosity measurement clearly indicate the preference for minor groove binding over intercalation, involving a change in Gibbs free energy of -8.56 kcal/mol. The 1â¢H2O complex was then evaluated for its anticancer potential in breast cancer MCF-7 cells, which severely abrogates the growth of the cells in both 2D and 3D mammospheres, indicating its promising application as an anticancer drug through a minor groove binding interaction with ct-DNA.
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Complejos de Coordinación , Bases de Schiff , Humanos , Manganeso/farmacología , Manganeso/química , Simulación del Acoplamiento Molecular , Complejos de Coordinación/química , ADN/químicaRESUMEN
The oligomeric form of amyloid-ß peptide (Aß42) plays a crucial role in the pathogenesis of Alzheimer's disease (AD) and is responsible for cognitive deficits. The soluble oligomers are believed to be more toxic compared to the fibril form. Protein-L-isoaspartyl methyltransferase (PIMT) is a repair enzyme that converts aberrant isoAsp residues, formed spontaneously on isomerization of normal Asp and Asn residues, back to typical Asp. It was shown to inhibit the fibrillization of Aß42 (containing three Asp residues), and here, we investigate its effect on the size, conformation, and toxicity of Aß42 oligomers (AßO). Far-UV CD indicated a shift in the conformational feature of AßOs from the random coil to ß-sheet in the presence of PIMT. Binding of bis-ANS to different AßOs (obtained using different concentrations of Aß42 monomer) indicated the correlation of size of oligomers to hydrophobicity: the smallest AßO having the highest hydrophobicity is the most toxic. Dynamic light scattering showed an increase in size of AßO with the addition of PIMT, a contrasting role to that on Aß fibril. Assays using PC12-derived neurons showed the neuroprotective role of PIMT against AßO-induced toxicity. Furthermore, we have elaborated on the molecular mechanism of the antifibrillar action of PIMT and how this function is correlated with its enzymatic activity. PIMT has a more pronounced effect on AßO as compared to a small heat shock protein, pointing to its importance for the amelioration of the adverse effect of both Aß42 oligomers and fibrils.
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Enfermedad de Alzheimer , Proteína D-Aspartato-L-Isoaspartato Metiltransferasa , Humanos , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Fragmentos de Péptidos/toxicidad , Proteína D-Aspartato-L-Isoaspartato Metiltransferasa/química , Proteína D-Aspartato-L-Isoaspartato Metiltransferasa/metabolismoRESUMEN
We aim to report about the clinico-pathological characteristics of early-age gastric cancer in North-East India. It is a retrospective and observational study conducted in a tertiary care cancer centre in North-East India. We reviewed physical case records and the hospital electronic medical record system. The study population included all patients of age 40 years or less, with a confirmed diagnosis of gastric adenocarcinoma, who received treatment in the institute. The duration of the study was from 2016 to 2020. Data was collected using a pre-designed proforma, and the results were presented as percentages, ratios, median values and range. A total of 79 patients with early-age gastric cancer were found during the study period. There was female preponderance (45:34). Out of the total, 43% presented in stage IV. Most of them had good performance status (87.3% had ECOG 0-2), and none of them had documented co-morbid illness. Poorly differentiated adenocarcinoma and signet ring cell carcinoma were seen in 36.7% and 25.3% patients, respectively. Only 25 patients (31.6%) underwent definitive surgery, and they had a high nodal burden with a median metastatic lymph nodal ratio of 0.35 (range 0 to 0.91). Out of them, 40% developed systemic recurrence within a short span of time (median time to recurrence being 9.5 months). Peritoneal recurrence was the most common site of failure (80%). Early-age gastric cancer has been associated with aggressive pathological features and poor clinical outcomes in North-East India.
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The aim of our study was to report about the clinical outcomes of patients who underwent major surgery for cancer and developed COVID-19 in the postoperative period. A retrospective and observational study was done in the Surgical Oncology Division of a tertiary care cancer hospital in North-East India. The study period was from 1st April 2020 to 31st December 2021. Patients with a confirmed diagnosis of cancer who underwent a major surgery and developed COVID-19 in the postoperative period, within the same hospital stay were included in the study. Data was obtained from a prospectively maintained database and case records. Descriptive statistics were used to state the results in median values, range and percentages. A total of 22 patients developed COVID-19 in the postoperative period during the study period out of a total of 1402 patients operated during that time period (1.57%). The have been followed up for a median period of 16 months (range 2 to 18 months). The median age at presentation was 50 years (range 25 to 74 years). The incidence of co-morbidities was 27.3%. The median duration of ICU stay was 3 days (range 0 to 9 days) and median duration of hospital stay was 22 days (range 9 to 55 days).. The postoperative mortality rate was 18.2%. COVID-19 in the postoperative period in patients undergoing major abdominal and thoracic surgeries for cancer caused high postoperative mortality and prolonged hospital stay.
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Background Approximately 1-2% of all scalp tumours are malignant, but they comprise up to 13% of all malignant cutaneous neoplasms. The current study presents our experience of reconstruction of scalp and forehead for malignant tumours treated at our centre. Methods This is a single institutional observational study conducted at a tertiary cancer centre in North East India. Post-operative outcomes related to quality of life of patients were measured with help of FACE-Q scales. Face-Q -Satisfaction with outcome and FACE-Q- appearance related psychosocial distress scores were analysed. Histograms were used for descriptive statistics. Data were checked for normality using Kolmogorov-Smirnova and Shapiro-Wilk test. For non-normal data Wilcoxon test was used. A p value less than 0.05 was considered as statistically significant at 5% level of significance. Results Mean age of patients was 57.6 ± 14.2 years. The mean defect size was 89.036 ± 81.77 cm2. The mean satisfaction with outcome scores and distress scores at 3-months was 54.9 ± 8.6 and 34.8 ± 8.5 respectively with a statistically significant p value of 0.001.Mean satisfaction scores and psychological distress scores were better at the end of three months when compared to at the time of discharge with a statistical significant p value of < 0.0001. Conclusion Scalp and forehead reconstructions for defects following oncological resections are technically challenging and if chosen carefully with meticulous planning, both local and free tissue transfers give satisfactory outcome in long term follow up. There are lots of reconstruction options for scalp and forehead defects and knowledge of the basic bio-geometry of the each flap is must.
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Neuropatías Amiloides Familiares , Amiloidosis , Cardiomiopatías , Cardiomiopatía Hipertrófica , Humanos , Prealbúmina/genética , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Amiloidosis/diagnóstico , Amiloidosis/diagnóstico por imagen , Cardiomiopatías/diagnóstico por imagen , Neuropatías Amiloides Familiares/diagnóstico , Neuropatías Amiloides Familiares/diagnóstico por imagenRESUMEN
Protein-protein interactions play a crucial role in microtubule dynamics. Microtubules are considered as a key target for the design and development of anticancer therapeutics, where inhibition of tubulin-tubulin interactions plays a crucial role. Here, we focused on a few key helical stretches at the interface of α,ß-tubulin heterodimers and developed a structural mimic of these helical peptides, which can serve as potent inhibitors of microtubule polymerization. To induce helicity, we have made stapled analogues of these sequences. Thereafter, we modified the lead sequences of the antimitotic stapled peptides with halo derivatives. It is observed that halo-substituted stapled peptides follow an interesting trend for the electronegativity of halogen atoms in interaction patterns with tubulin and a correlation in the toxicity profile. Remarkably, we found that para-fluorophenylalanine-modified stapled peptide is the most potent inhibitors, which perturbs microtubule dynamics, induces apoptotic death, and inhibits the growth of melanoma.
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Antimitóticos , Tubulina (Proteína) , Tubulina (Proteína)/química , Moduladores de Tubulina/farmacología , Antimitóticos/farmacología , p-Fluorofenilalanina , Péptidos/farmacología , Microtúbulos , HalógenosRESUMEN
The neural basis of behavior is identified by systematically manipulating the activity of specific neurons and screening for loss or gain of phenotype. Therefore, robust, high-scoring behavioral assays are necessary for determining the neural circuits of novel behaviors. We report a simple Y-maze design for Drosophila olfactory learning and memory assay. Memory scores in our Y-mazes are considerably better and longer-lasting than scores obtained with commonly used T-mazes. Our results suggest that trapping flies to an odor choice in a Y-maze could improve scores. We postulated that the improved scores could reveal previously undetectable memory traces, enabling the study of underlying neural mechanisms. Indeed, we identified unreported protein synthesis-dependent long-term memories (LTMs), reinforced by ingestion of (1) an aversive compound and (2) a sweet but nonnutritious sugar, both 24 h after training. We also used Y-mazes to probe how using a greater reward may change memory dynamics. Our findings predict that a greater sugar reward may extend existing memory traces or reinforce additional novel ones.
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Drosophila , Olfato , Animales , Condicionamiento Clásico/fisiología , Drosophila/fisiología , Drosophila melanogaster/fisiología , Odorantes , Olfato/fisiología , AzúcaresRESUMEN
Pelvic exenteration is a surgery done to achieve margin negative resection in locally advanced rectal cancer infiltrating pelvic organs anterior to it. A retrospective observational study of patients undergoing pelvic exenteration for locally advanced rectal cancer was done at a single surgical unit of a tertiary care cancer centre. The period of study was from 1st January 2019 to 30th June 2021. A total of twelve patients underwent pelvic exenteration for locally advanced rectal cancer during the study period. The median duration of surgery was 310 min (range 250 to 380 min). The median duration of hospital stay was 14 days (range 12 to 30 days). Seven patients had documented postoperative complications, either major or minor, with a complication rate of 58.3%. Three patients required re-admission for complications. Two patients had COVID19 infection in the postoperative period but had uneventful recovery. Margin negative resection (R0) was achieved in eight patients (66.67%). Pelvic exenteration for locally advanced rectal cancer is a definitive surgery associated with a high morbidity rate. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-022-01529-3.
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BACKGROUND: Early prediction of response to percutaneous catheter drainage (PCD) of necrotic collections in acute pancreatitis (AP) using simple and objective tests is critical as it may determine patient prognosis. The role of white blood cell (WBC) count and neutrophil-lymphocyte ratio (NLR) has not been assessed as a tool of early prediction of PCD success and is the focus of this study. AIM: To assess the value of WBC and NLR in predicting response to PCD in AP. METHODS: This retrospective study comprised consecutive patients with AP who underwent PCD between June 2018 and December 2019. Severity and fluid collections were classified according to the revised Atlanta classification and organ failure was defined according to the modified Marshall Score. WBC and NLR were monitored 24 h prior PCD (WBC-0/NLR-0) and 24 h (WBC-1/NLR-1), 48 h (WBC-2/NLR-2) and 72 h (WBC-3/NLR-3) after PCD. NLR was calculated by dividing the number of neutrophils by the number of lymphocytes. The association of success of PCD (defined as survival without the need for surgery) with WBC and NLR was assessed. The trend of WBC and NLR was also assessed post PCD. RESULTS: One hundred fifty-five patients [median age 40 ± 13.6 (SD), 64.5% males, 53.5% severe AP] were included in the final analysis. PCD was done for acute necrotic collection in 99 (63.8%) patients and walled-off necrosis in 56 (36.1%) patients. Median pain to PCD interval was 24 ± 69.89 d. PCD was successful in 109 patients (group 1) and 46 patients (group 2) who failed to respond. There was no significant difference in the baseline characteristics between the two groups except the severity of AP and frequency of organ failure. Both WBC and NLR showed an overall decreasing trend. There was a significant difference between WBC-0 and WBC-1 (P = 0.0001). WBC-1 and NLR-1 were significantly different between the two groups (P = 0.048 and 0.003, respectively). The area under the curve of WBC-1 and NLR-1 for predicting the success of PCD was 0.602 and 0.682, respectively. At a cut-off value of 9.87 for NLR-1, the sensitivity and specificity for predicting the success of PCD were calculated to be 75% and 65.4% respectively. CONCLUSION: WBC and NLR can be used as simple tests for predicting response to PCD in patients with acute necrotizing pancreatitis.