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1.
Biotechnol Lett ; 46(3): 297-314, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38607602

RESUMO

Scientists are making efforts to search for new metabolites as they are essential lead molecules for the drug discovery, much required due to the evolution of multi drug resistance and new diseases. Moreover, higher production of known drugs is required because of the ever growing population. Microorganisms offer a vast collection of chemically distinct compounds that exhibit various biological functions. They play a crucial role in safeguarding crops, agriculture, and combating several infectious ailments and cancer. Research on fungi have grabbed a lot of attention after the discovery of penicillin, most of the compounds produced by fungi under normal cultivation conditions are discovered and now rarely new compounds are discovered. Treatment of fungi with the epigenetic modifiers has been becoming very popular since the last few years to boost the discovery of new molecules and enhance the production of already known molecules. Epigenetic literally means above genetics that actually does not alter the genome but alter its expression by altering the state of chromatin from heterochromatin to euchromatin. Chromatin in heterochromatin state usually doesn't express because it is closely packed by histones in this state. Epigenetic modifiers loosen the packing of chromatin by inhibiting DNA methylation and histone deacetylation and thus permit the expression of genes that usually remain dormant. This study delves into the possibility of utilizing epigenetic modifying agents to generate pharmacologically significant secondary metabolites from fungi.


Assuntos
Epigênese Genética , Fungos , Metabolismo Secundário , Fungos/genética , Fungos/metabolismo , Fungos/efeitos dos fármacos , Metabolismo Secundário/genética , Metilação de DNA
2.
Future Med Chem ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38596902

RESUMO

Aim: p-Toluenesulfonic acid-(PTSA) and grinding-induced novel synthesis of ethylquinolin-thiazolo-triazole derivatives was performed using green chemistry. Materials & methods: Development of a nanoconjugate drug-delivery system of ethylquinolin-thiazolo-triazole was carried out with D-α-tocopheryl polyethylene glycol succinate (TPGS) and the formulation was further characterized by transmission electron microscopy, atomic force microscopy, dynamic light scattering and in vitro drug release assay. The effect of 3a nanoparticles was assessed against a cervical cancer cell line (HeLa) through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the effect on apoptosis was determined. Results & discussion: The 3a nanoparticles triggered the apoptotic mode of cell death after increasing the intracellular reactive oxygen level by enhancing cellular uptake of micelles. Furthermore, in silico studies revealed higher absorption, distribution, metabolism, elimination and toxicity properties and bioavailability of the enzyme tyrosine protein kinase. Conclusion: The 3a nanoparticles enhanced the therapeutic potential and have higher potential for targeted drug delivery against cervical cancer.

3.
Indian J Gastroenterol ; 43(1): 36-47, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38383877

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that encompasses two major conditions: Crohn's disease (CD) and ulcerative colitis (UC). Historically, IBD has been primarily reported in western countries, but over the past decades, its prevalence is rapidly increasing, especially in lower and middle-income countries (LMICs) such as India and China and also in Sub-Saharan Africa. The prevalence of IBD in LMICs has been the subject of growing concern due to the impact of access to public healthcare and the burden it places on healthcare resources. The classical thiopurines face significant challenges due to cessation of therapy in approximately half of patients within one year due to side effects or ineffectiveness. In this article, we highlight innovating thiopurine treatment for IBD patients in downregulating side effects and improving efficacy.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Purinas , Compostos de Sulfidrila , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Mercaptopurina , Azatioprina/uso terapêutico , Imunossupressores/efeitos adversos
4.
Indian J Gastroenterol ; 43(1): 22-35, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38347433

RESUMO

Rising number of inflammatory bowel disease (IBD) cases in developing countries necessitate clear guidance for clinicians for the appropriate use of advanced therapies. An expert consensus document was generated to guide the usage of tofacitinib, a Janus kinase inhibitor, in ulcerative colitis. Tofacitinib is a useful agent for the induction and maintenance of remission in ulcerative colitis. It can be used in the setting of biological failure or even steroid-dependent and thiopurine refractory disease. Typically, the induction dose is 10 mg BD orally. Usually, clinical response is evident within eight weeks of therapy. In those with clinical response, the dose can be reduced from 10 mg BD to 5 mg BD. Tofacitinib should be avoided or used cautiously in the elderly, patients with cardiovascular co-morbidity, uncontrolled cardiac risk factors, previous thrombotic episodes and those at high risk for venous thrombosis or previous malignancy. Baseline evaluation should include testing for and management of hepatitis B infection and latent tuberculosis. Where feasible, it is prudent to ensure complete adult vaccination, including Herpes zoster, before starting tofacitinib. The use of tofacitinib may be associated with an increased risk of infections such as herpes zoster and tuberculosis reactivation. Maternal exposure to tofacitinib should be avoided during pre-conception, pregnancy, and lactation. There is emerging evidence of tofacitinib in acute severe colitis, although the exact positioning (first-line with steroids or second-line) is uncertain.


Assuntos
Colite Ulcerativa , Colite , Herpes Zoster , Pirimidinas , Adulto , Feminino , Humanos , Idoso , Colite Ulcerativa/tratamento farmacológico , Consenso , Piperidinas/efeitos adversos , Herpes Zoster/induzido quimicamente , Herpes Zoster/tratamento farmacológico
5.
J Clin Exp Hepatol ; 14(3): 101348, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389867

RESUMO

Background: Biliary obstruction in gallbladder cancer (GBC) is associated with worse prognosis and needs drainage. In patients with biliary confluence involvement, percutaneous biliary drainage (PBD) is preferred over endoscopic drainage. However, PBD catheters are associated with higher complications compared to endoscopic drainage. PBD with self-expandable metal stents (SEMS) is desirable for palliation. However, the data in patients with unresectable GBC is lacking. Materials and methods: This retrospective study comprised consecutive patients with proven GBC who underwent PBD-SEMS insertion between January 2021 and December 2022. Technical success, post-procedural complications, clinical success, duration of stent patency, and biliary reinterventions were recorded. Clinical follow-up data was analysed at 30 days and 180 days of SEMS insertion and mortality was recorded. Results: Of the 416 patients with unresectable GBC, who underwent PBD, 28 (median age, 50 years; 16 females) with PBD-SEMS insertion were included. All SEMS placement procedures were technically successful. There were no immediate/early post-procedural complications/deaths. The procedures were clinically successful in 63.6% of the patients with hyperbilirubinemia (n = 11). Biliary re-interventions were done in 6 (21.4%). The survival rate was 89.3 % (25/28) at 30 days and 50% at 180 days. The median follow-up duration was 80 days (range, 8-438 days). Conclusion: PBD-SEMS has moderate clinical success and 6-months patency in almost half of the patients with metastatic GBC and must be considered for palliation.

6.
Indian J Gastroenterol ; 43(1): 145-159, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38376725

RESUMO

There is abundant literature reporting about the use of antibiotics in inflammatory bowel disease (IBD), but their role in the management of IBD is not entirely clear. Diverse infectious organisms have been implicated in the pathogenesis of Crohn's disease. Also, infections are believed to be a trigger for flares of ulcerative colitis. The benefit of the routine use of antibiotics in IBD is equivocal. However, there are certain situations, where antibiotics have a clear role and evidence of benefit: perianal fistula, intra-abdominal abscesses in Crohn's disease, acute pouchitis and infection-related flares. However, there is a lack of supportive evidence for the routine use of antibiotics in all disease-related flares. Evidence indicates a lack of benefit of intravenous antibiotics in acute severe ulcerative colitis and only limited benefit in active ulcerative colitis. Limited evidence suggests the role of a combination of oral antibiotics in pediatric ulcerative colitis. Certain targeted antibiotic regimens have been used in IBD. In ulcerative colitis, limited evidence suggests the benefit of the use of an antibiotic cocktail directed against Fusobacterium varium. Therapy directed against Escherichia coli does not seem to have a benefit in inflammatory Crohn's disease. In Crohn's disease, antimycobacterial therapy may result in symptomatic improvement but no durable benefit. Antitubercular therapy (ATT), on the contrary, may result in fibrotic transformation, suggesting a need to avoid misdiagnosis and limit the duration of ATT in Crohn's disease. This review assesses the published literature with respect to antibiotic use and provides guidance to clinicians in appropriate antibiotic use in various situations in the setting of IBD.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Fístula Retal , Criança , Humanos , Colite Ulcerativa/diagnóstico , Doença de Crohn/microbiologia , Antibacterianos/uso terapêutico , Doenças Inflamatórias Intestinais/microbiologia
7.
J Gastroenterol Hepatol ; 39(3): 422-430, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38058246

RESUMO

BACKGROUND AND AIM: Discrimination of gastrointestinal tuberculosis (GITB) and Crohn's disease (CD) is difficult. Use of artificial intelligence (AI)-based technologies may help in discriminating these two entities. METHODS: We conducted a systematic review on the use of AI for discrimination of GITB and CD. Electronic databases (PubMed and Embase) were searched on June 6, 2022, to identify relevant studies. We included any study reporting the use of clinical, endoscopic, and radiological information (textual or images) to discriminate GITB and CD using any AI technique. Quality of studies was assessed with MI-CLAIM checklist. RESULTS: Out of 27 identified results, a total of 9 studies were included. All studies used retrospective databases. There were five studies of only endoscopy-based AI, one of radiology-based AI, and three of multiparameter-based AI. The AI models performed fairly well with high accuracy ranging from 69.6-100%. Text-based convolutional neural network was used in three studies and Classification and regression tree analysis used in two studies. Interestingly, irrespective of the AI method used, the performance of discriminating GITB and CD did not match in discriminating from other diseases (in studies where a third disease was also considered). CONCLUSION: The use of AI in differentiating GITB and CD seem to have acceptable accuracy but there were no direct comparisons with traditional multiparameter models. The use of multiple parameter-based AI models have the potential for further exploration in search of an ideal tool and improve on the accuracy of traditional models.


Assuntos
Doença de Crohn , Tuberculose Gastrointestinal , Humanos , Inteligência Artificial , Doença de Crohn/diagnóstico por imagem , Redes Neurais de Computação , Estudos Retrospectivos , Tuberculose Gastrointestinal/diagnóstico , Diagnóstico por Computador
8.
Med Chem ; 20(1): 17-29, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37815177

RESUMO

Despite extensive research in the field of drug discovery and development, still there is a need to develop novel molecular entities. Literature reveals a substantial heterocyclic nucleus named, piperazine, which shows an immense therapeutic voyage. For several decades, molecules having the piperazine nucleus have entered the market as a drug exhibiting biological potential. It was known to possess antipsychotic, antihistamine, antianginal, antidepressant, anticancer, antiviral, cardioprotective, and anti-inflammatory activity with a specific basis for structural activity relationship. Thus, it is regarded as a key structural feature in most of the already available therapeutic drugs in the market. Reports also suggest that the extensive utilization of these currently available drugs having a piperazine nucleus shows increasing tolerance significantly day by day. In addition to this, various other factors like solubility, low bioavailability, cost-effectiveness, and imbalance between pharmacokinetics and pharmacodynamics profile limit their utilization. Focusing on that issues, various structural modification studies were performed on the piperazine moiety to develop new derivatives/analogs to overcome the problems associated with available marketed drugs. Thus, this review article aims to gain insight into the number of structural modifications at the N-1 and N-4 positions of the piperazine scaffold. This SAR approach may prove to be the best way to overcome the above-discussed drawbacks and lead to the design of drug molecules with better efficacy and affinity. Hence, there is an urgent need to focus on the structural features of this scaffold which paves further work for deeper exploration and may help medicinal chemists as well as pharmaceutical industries.


Assuntos
Descoberta de Drogas , Piperazina , Relação Estrutura-Atividade
9.
Am J Gastroenterol ; 119(1): 176-182, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37732816

RESUMO

INTRODUCTION: Successful biliary drainage and antibiotics are the mainstays of therapy in management of patients with acute cholangitis. However, the duration of antibiotic therapy after successful biliary drainage has not been prospectively evaluated. We conducted a single-center, randomized, noninferiority trial to compare short duration of antibiotic therapy with conventional duration of antibiotic therapy in patients with moderate or severe cholangitis. METHODS: Consecutive patients were screened for the inclusion criteria and randomized into either conventional duration (CD) group (8 days) or short duration (SD) group (4 days) of antibiotic therapy. The primary outcome was clinical cure (absence of recurrence of cholangitis at day 30 and >50% reduction of bilirubin at day 15). Secondary outcomes were total days of antibiotic therapy and hospitalization within 30 days, antibiotic-related adverse events, and all-cause mortality at day 30. RESULTS: The study included 120 patients (the mean age was 55.85 ± 13.52 years, and 50% were male patients). Of them, 51.7% patients had malignant etiology and 76.7% patients had moderate cholangitis. Clinical cure was seen in 79.66% (95% confidence interval, 67.58%-88.12%) patients in the CD group and 77.97% (95% confidence interval, 65.74%-86.78%) patients in the SD group ( P = 0.822). On multivariate analysis, malignant etiology and hypotension at presentation were associated with lower clinical cure. Total duration of antibiotics required postintervention was lower in the SD group (8.58 ± 1.92 and 4.75 ± 2.32 days; P < 0.001). Duration of hospitalization and mortality were similar in both the groups. DISCUSSION: Short duration of antibiotics is noninferior to conventional duration in patients with moderate-to-severe cholangitis in terms of clinical cure, recurrence of cholangitis, and overall mortality.


Assuntos
Antibacterianos , Colangite , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Doença Aguda , Colangite/tratamento farmacológico , Colangite/etiologia
11.
Chemistry ; 30(12): e202303957, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38051591

RESUMO

The reaction of a nickel(II) chloride complex containing a tridentate ß-diketiminato ligand with a picolyl group [2,6-iPr2 -C6 H3 NC(Me)CHC(Me)NH(CH2 py)]Ni(II)Cl (1)] with KSi(SiMe3 )3 conveniently afforded a nickel(I) radical with a T-shaped geometry (2). The compound's metalloradical nature was confirmed through electron paramagnetic resonance (EPR) studies and its reaction with TEMPO, resulting in the formation of a highly unusual three-membered nickeloxaziridine complex (3). When reacted with disulfide and diselenide, the S-S and Se-Se bonds were cleaved, and a coupled product was formed through carbon atom of the pyridine-imine group. The nickel(I) radical activates dihydrogen at room temperature and atmospheric pressure to give the monomeric nickel hydride.

12.
Curr Probl Diagn Radiol ; 53(2): 259-270, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37923635

RESUMO

Autoimmune gastrointestinal (GI) disorders comprise a heterogeneous group of diseases with non-specific clinical manifestations. These are divided into primary and secondary. A high index of clinical suspicion complemented with endoscopic and radiological imaging may allow early diagnosis. Due to the relatively low incidence of autoimmune disorder, the imaging literature is sparse. In this review, we outline the pathogenesis, classification, and imaging appearances of autoimmune GI disorders.


Assuntos
Gastroenteropatias , Trato Gastrointestinal , Humanos , Trato Gastrointestinal/diagnóstico por imagem , Gastroenteropatias/diagnóstico por imagem , Endoscopia/métodos , Radiografia , Diagnóstico por Imagem/métodos , Endoscopia Gastrointestinal/métodos
13.
J Clin Exp Hepatol ; 14(1): 101276, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38076364

RESUMO

Background/Aim: Hepatocellular carcinoma (HCC) surveillance is recommended in nonalcoholic fatty liver disease (NAFLD)-related cirrhosis. The performance of ultrasound (US) is impaired in NAFLD. This study aimed to evaluate the diagnostic performance of non-contrast abbreviated magnetic resonance imaging (AMRI) for HCC detection in NAFLD. Methods: Consecutive contrast-enhanced magnetic resonance imaging (CE-MRI) scans of NAFLD patients between June 2017 and December 2021 were retrieved. A radiologist extracted and anonymized a noncontrast AMRI dataset comprising T2-weighted, T1-weighted, and diffusion-weighted imaging (DWI) sequences. Two radiologists blinded to CE-MRI reports and treatment details independently reviewed the AMRI for liver lesion and portal vein (PV) characteristics. HCC and malignant PV thrombosis were diagnosed based on the original dynamic CE-MRI diagnostic reports. The diagnostic performance of AMRI and the interobserver agreement for detecting HCC and malignant PV thrombosis were calculated. Results: Seventy-five patients (52 males; mean age (±SD), 56 ± 17.6 years; 61 cirrhotic) were included. Nine patients had HCC (14 HCCs). The sensitivity, specificity, positive predictive value, and negative predictive value of AMRI for detecting HCC were 100%, 93.9%, 69.2%, and 100%, respectively, and malignant PV thrombosis was 100%, 98.5%, 80%, and 100%, respectively. There was substantial interobserver agreement for detecting HCC (kappa = 0.721) and malignant PV thrombosis (kappa = 0.645) on AMRI. Conclusion: AMRI has high diagnostic performance in HCC detection in patients with NAFLD. However, prospective studies must compare the diagnostic performance of AMRI with that of US.

14.
Dig Dis Sci ; 69(2): 335-348, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38114791

RESUMO

Pancreatic fistula is a highly morbid complication of pancreatitis. External pancreatic fistulas result when pancreatic secretions leak externally into the percutaneous drains or external wound (following surgery) due to the communication of the peripancreatic collection with the main pancreatic duct (MPD). Internal pancreatic fistulas include communication of the pancreatic duct (directly or via intervening collection) with the pleura, pericardium, mediastinum, peritoneal cavity, or gastrointestinal tract. Cross-sectional imaging plays an essential role in the management of pancreatic fistulas. With the help of multiplanar imaging, fistulous tracts can be delineated clearly. Thin computed tomography sections and magnetic resonance cholangiopancreatography images may demonstrate the communication between MPD and pancreatic fluid collections or body cavities. Endoscopic retrograde cholangiography (ERCP) is diagnostic as well as therapeutic. In this review, we discuss the imaging diagnosis and management of various types of pancreatic fistulas with the aim to sensitize radiologists to timely diagnosis of this critical complication of pancreatitis.


Assuntos
Pancreatopatias , Pancreatite , Humanos , Fístula Pancreática/diagnóstico por imagem , Fístula Pancreática/etiologia , Fístula Pancreática/terapia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Pancreatite/complicações , Pancreatite/diagnóstico por imagem , Pâncreas/diagnóstico por imagem , Pancreatopatias/patologia , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/patologia , Imageamento por Ressonância Magnética
15.
Artigo em Inglês | MEDLINE | ID: mdl-38102523

RESUMO

BACKGROUND: Endoscopic ultrasound (EUS)-guided drainage is the standard of care for drainage of pancreatic necrosis. Though initially it was mainly used for drainage of only walled-off necrosis, recently, a few studies have also shown its safety in the management of acute necrotic collections. We did a retrospective study to evaluate the safety and efficacy of EUS-guided drainage in the early phase of pancreatitis as compared to interventions in the late phase. METHODS: We retrieved baseline disease-related, procedure-related and outcome-related details of patients who underwent EUS-guided drainage of pancreatic necrosis. Patients were divided into early (≤ 28 days from onset of pancreatitis) or delayed (> 28 days) drainage groups. Both groups were compared for disease-related characteristics and outcomes. RESULTS: Total 101 patients were included in the study. The mean age of included patients was 35.54 ± 13.58 years and 75 were male. Thirty-five patients (34.7%) underwent early drainage. In the early group, a majority of patients underwent intervention due to infected collection (88.6% vs. 18.2%; p < 0.001). More patients in the early group had < 30% wall formation (28.6% vs. 0%; p < 0.001) and > 30% solid debris within the collection (42.9% vs. 15.2%; p = 0.005). Patients in the early group were also more likely to require endoscopic necrosectomy (57.1% vs. 27.3%; p = 0.003) and additional percutaneous drainage (31.4% vs. 12.1%; p = 0.018). Overall, three patients in the early group and one patient in the delayed group had procedure-related complications. Four patients in the early group and one patient in the delayed group succumbed to illness (p = 0.029). CONCLUSION: Though delayed interventions remain standard of care in the management of acute pancreatitis, some patients may require early intervention due to infected collection with deteriorating clinical status. Early EUS-guided interventions in such carefully selected patients have in similar clinical outcomes and complication rates compared to delayed intervention. However, such patients are more likely to require additional endoscopic or percutaneous interventions.

16.
Curr Drug Metab ; 24(12): 787-802, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38141188

RESUMO

BACKGROUND: Cancer drug resistance remains a difficult barrier to effective treatment, necessitating a thorough understanding of its multi-layered mechanism. OBJECTIVE: This study aims to comprehensively explore the diverse mechanisms of cancer drug resistance, assess the evolution of resistance detection methods, and identify strategies for overcoming this challenge. The evolution of resistance detection methods and identification strategies for overcoming the challenge. METHODS: A comprehensive literature review was conducted to analyze intrinsic and acquired drug resistance mechanisms, including altered drug efflux, reduced uptake, inactivation, target mutations, signaling pathway changes, apoptotic defects, and cellular plasticity. The evolution of mutation detection techniques, encompassing clinical predictions, experimental approaches, and computational methods, was investigated. Strategies to enhance drug efficacy, modify pharmacokinetics, optimizoptimizee binding modes, and explore alternate protein folding states were examined. RESULTS: The study comprehensively overviews the intricate mechanisms contributing to cancer drug resistance. It outlines the progression of mutation detection methods and underscores the importance of interdisciplinary approaches. Strategies to overcome drug resistance challenges, such as modulating ATP-binding cassette transporters and developing multidrug resistance inhibitors, are discussed. The study underscores the critical need for continued research to enhance cancer treatment efficacy. CONCLUSION: This study provides valuable insights into the complexity of cancer drug resistance mechanisms, highlights evolving detection methods, and offers potential strategies to enhance treatment outcomes.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Neoplasias/metabolismo , Transporte Biológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/metabolismo
17.
Int J Mol Cell Med ; 12(1): 1-17, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37942260

RESUMO

Leukemia is a type of cancer that affects the blood and bone marrow. Acute lymphoid leukaemia, also known as ALL, is regarded as one of the deadliest forms of cancer. Due to the rapid increase in various cancer cases and the development of resistance in cancer cells, it is necessary to identify novel lead molecules with more potent anticancer properties. There is a growing interest in using herbal products/analogs as multi-component agents (as anticancer agents and immunomodulators) for cancer treatment. In the present investigation, an attempt has been made to explore the anticancer and immunomodulatory activity of P19, an analog of parthenin in ALL. P19 was reported to exhibit anticancer efficacy by triggering apoptotic signaling events in human leukaemia HL-60 cells by significant NO production. In contrast to this finding, ROS and NO were not required for P19-mediated apoptosis in Raji cells. The mechanism of action of P19 was observed to be cancer cell lineage dependent. P19 demonstrated very effective anticancer properties against ALL (IC50 3µM). Molecular investigations revealed that P19 induced mitochondrion mediated apoptosis by Bax localization to mitochondria and enhanced cytosolic calcium in the cytoplasm. Further activation of the caspase 3, caspase 8 and PARP cleavage suggested the involvement of the caspase-mediated apoptosis. Anti-proliferative activity revealed the telomerase inhibition and cell cycle arrest in G0/G1 phase after P19 treatment. Immunomodulatory effects of the P19 revealed the enhanced INFÉ£ and NO production in Jurkat and THP cells. Owing to its antiproliferative and immunomodulatory potential against leukemia cells P19 can further be explored as effective therapeutics against leukemia.

18.
Indian J Surg Oncol ; 14(3): 694-698, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37900661

RESUMO

Infectious complications following oesophagectomy are associated with significant morbidity. Early prediction of these complications may mitigate significant morbidity and mortality. Patients undergoing minimally invasive oesophagectomy for carcinoma oesophagus between January 2019 and June 2020 were included in the study. All patients underwent standard preoperative investigations and preparation. Post-operative complications including infectious complications were recorded. Association of post-operative serum interleukin-6 (IL-6) levels with post-operative complications were analysed. A total of twenty-two participants were included in the study (median age; 51 years, 13 (%) male). The tumour site was middle 1/3rd of oesophagus in 13 (59.1%), lower 1/3rd of oesophagus in 9 (40.9%). The tumour histology was squamous cell carcinoma in all patients. Eight (36.4 %) patients developed major complications and five of them developed anastomotic leak. IL-6 levels were significantly higher on POD 3 in patients who developed major complications (p = 0.009) and anastomotic leak (p = 0.031). At receiver operating characteristic curve (ROC curve) analysis, an IL-6 cut-off level of 36.4 pg/ml on POD 3 yielded a sensitivity of 87% and a specificity of 79% for the prediction of major complication and cut-off level of 44.3 pg/ml on POD 3 yielded a sensitivity of 80% and a specificity of 82% for the prediction of anastomotic leak. A high post-operative IL-6 level helps in the prediction of major complications and cervical oesophagogastric anastomotic leak.

19.
Diagnostics (Basel) ; 13(20)2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37892027

RESUMO

It is challenging to differentiate between tuberculous peritonitis and peritoneal carcinomatosis due to their insidious nature and intersecting symptoms. Computed tomography (CT) is the modality of choice in evaluating diffuse peritoneal disease. We conducted an ambispective analysis of patients suspected as having tuberculous peritonitis or peritoneal tuberculosis between Jan 2020 to Dec 2021. The study aimed to identify the clinical and radiological features differentiating the two entities. We included 44 cases of tuberculous peritonitis and 45 cases of peritoneal carcinomatosis, with a median age of 31.5 (23.5-40) and 52 (46-61) years, respectively (p ≤ 0.001). Fever, past history of tuberculosis, and loss of weight were significantly associated with tuberculous peritonitis (p ≤ 0.001, p = 0.038 and p = 0.001). Pain in the abdomen and history of malignancy were significantly associated with peritoneal carcinomatosis (p = 0.038 and p ≤ 0.001). Ascites was the most common radiological finding. Loculated ascites, splenomegaly and conglomeration of lymph nodes predicted tuberculous peritonitis significantly (p ≤ 0.001, p = 0.010, p = 0.038). Focal liver lesion(s) and nodular omental involvement were significantly associated with peritoneal carcinomatosis (p = 0.011, p = 0.029). The use of clinical features in conjunction with radiological findings provide better diagnostic yields because of overlapping imaging findings.

20.
Asian Biomed (Res Rev News) ; 17(2): 72-83, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37719323

RESUMO

Background: In rapidly growing solid tumors, insufficient vascularization and poor oxygen supply result in an acidic tumor microenvironment, which can alter immune response. Objective: To investigate the role of the acidic microenvironment in immune response modulation along with cancer and immune cells' interactions. Method: To mimic the tumor microenvironment conditions, T cells (Jurkat), macrophages (THP-1), and HeLa (cervical) cells were cultured under acidic conditions (pH 6.9, pH 6.5) and physiological pH (7.4). The HeLa cell culture medium was exploited as a tumor cell conditioned medium. Real-time PCR was carried out to quantify the mRNA levels, while flow cytometry and western blot hybridization was carried out to ascertain the levels of different proteins. Results: The acidic microenvironment around the T cells (Jurkat) and macrophage cells (THP-1) could lead to the downregulation of the interferon gamma (IFN-γ). An increase in IFN-γ expression was observed when Jurkat and macrophage cells were cultured in HeLa cells conditioned medium (HCM) at low pH (pH 6.9, pH 6.5). The HeLa cells under acidic environment (pH 6.9, pH 6.5) upregulated interleukin 18 levels and secreted it as exosome anchored. Additionally, enhanced nuclear localization of NF-κB was observed in Jurkat and THP-1 cells cultured in HCM (pH 6.9, pH 6.5). Jurkat and THP-1 cultured in HCM revealed enhanced cytotoxicity against the HeLa cells upon reverting the pH of the medium from acidic to physiological pH (pH 7.4). Conclusion: Collectively, these results suggest that the acidic microenvironment acted as a key barrier to cancer and immune cells' interactions.

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