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Chronic diseases like cancer and diabetes are the major public health concerns of India and worldwide. Nowadays, plant-derived products are in great demand for the treatment of these diseases. Pumpkin seeds are traditionally implicated for their pharmacological properties, as exemplified by benign prostatic hyperplasia. Earlier, pumpkin seed proteins were extracted by the Osborne method, and their functional and nutritional qualities were evaluated. Here, the aim is to assess in vitro, the anticancer and antidiabetic properties of seed protein fractions. HepG2, MDA-MB-231, and MCF-7 cell lines were treated with water-soluble (WF) and alkali-soluble fractions (AF) to assess cytotoxicity, while pancreatic ß-cells and insulin resistance (IR) - HepG2 cell lines were treated with WF to evaluate the antidiabetic potential. WF and AF showed cytotoxic effects towards HepG2 and MDA-MB-231 cell lines, suggesting apoptosis-mediated anticancerous activity. WF potentiates glucose-stimulated insulin secretion in pancreatic ß-cells, in a dose-dependent manner. In IR-HepG2 cell line studies, control, metformin, and WF-treated groups showed uptake of glucose, when compared to the diabetic group, which is well-correlated with the upregulated expressions of GLUT2 and GLUT4 transporters in these groups. These results indicate that proteins from WF and AF may have anticancerous and antidiabetic properties and thus have the potential to utilize pumpkin proteins in the management of cancer and diabetes.
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This study investigated the reproductive toxicity of rhodamine B in zebrafish and its transgenerational effects on the F1 generation. In silico toxicity predictions revealed high toxicity of rhodamine B, mainly targeting pathways associated with the reproductive and endocrine systems. In vivo experiments on zebrafish demonstrated that rhodamine B exposure at a concentration of 1.5 mg/L led to significant impairments in fecundity parameters, particularly affecting females. Histopathological analysis revealed distinct changes in reproductive organs, further confirming the reproductive toxicity of rhodamine B, with females being more susceptible than males. Gene expression studies indicated significant suppression of genes crucial for ovulation in rhodamine B-treated female fish, highlighting hormonal imbalance as a potential mechanism of reproductive toxicity. Furthermore, bioaccumulation studies showed the presence of rhodamine B in both adult fish gonads and F1 generation samples, suggesting transgenerational transfer of the dye. Embryotoxicity studies on F1 generation larvae demonstrated reduced survival rates, lower hatching rates, and increased malformations in groups exposed to rhodamine B. Moreover, rhodamine B induced oxidative stress in F1 generation larvae, as evidenced by elevated levels of reactive oxygen species and altered antioxidant enzyme activity. Neurotoxicity assessments revealed reduced acetylcholinesterase activity, indicating potential neurological impairments in F1 generation larvae. Additionally, locomotory defects and skeletal abnormalities were observed in F1 generation larvae exposed to rhodamine B. This study provides comprehensive evidence of the reproductive toxicity of rhodamine B in adult zebrafish and its transgenerational effects on the F1 generation.
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Rodaminas , Contaminantes Químicos del Agua , Pez Cebra , Masculino , Animales , Femenino , Pez Cebra/metabolismo , Acetilcolinesterasa/metabolismo , Reproducción , Gónadas , Contaminantes Químicos del Agua/metabolismoRESUMEN
Paraprobiotics, known as non-viable or ghost probiotics, have attracted attention for their benefits over live microbial cells. This study was designed to investigate the paraprobiotic effects of heat-killed Bacillus coagulans on the white leg shrimp Litopenaeus vannamei. The paraprobiotic formulation was prepared in three different concentrations including B. coagulans 1 (107 cells g-1 diet), B. coagulans 2 (108 cells g-1 diet), and B. coagulans 3 (109 cells g-1 diet) through heat inactivation method. Preliminary toxicity assessments revealed that post-larvae shrimps (mean weight ± SE: 0.025 ± 0.007 g) treated with B. coagulans 1, 2 and 3 paraprobiotic formulations exhibited no mortality, confirming the non-toxic nature of the formulated diet. In a 90-day feeding trial involving juvenile shrimps (mean weight ± SE: 0.64 ± 0.05 g), growth parameters and feed conversion ratios improved in all experimental groups. Subsequently, these shrimps were challenged with Vibrio parahaemolyticus, revealing that paraprobiotic-fed shrimps exhibited significant survival rate improvements. Oxidative stress-related enzyme activities, such as superoxide dismutase and catalase, increased in paraprobiotic-fed shrimps post-Vibrio challenge, while the challenged control group showed decreased activity (p < 0.001). Nitric oxide levels are also increased in paraprobiotic-treated shrimp, with B. coagulans 3 showing a significant rise in nitric oxide activity (p < 0.001). This study further demonstrated the positive impact of paraprobiotic treatment on digestive enzymes, immune-related parameters (e.g., total hemocyte count, prophenoloxidase, and respiratory burst activity), and overall disease resistance. These findings suggest that B. coagulans paraprobiotics have the potential to enhance antioxidant, antibacterial, and immune-related responses in L. vannamei, making them a valuable addition to shrimp aquaculture.
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Phyllodes tumors are rare biphasic fibroepithelial lesions of the breast and account for 0.3%-0.5% of primary breast tumors. Malignant phyllodes tumor has a 10%-26% risk of distant metastasis. The most common site of metastasis is lungs followed by bone and soft tissue. This is a rare case of a 42-year-old female with a previous history of malignant phyllodes tumor breast. She presented after 10 years with metastases to multiple sites including lung, abdominal wall, retroperitoneum, bone, and brain. These tumors have a poor overall survival. Accurate diagnosis and aggressive management of malignant phyllodes tumors can help in effective treatment at diagnosis and for close follow-up of the patients.
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Neoplasias de la Mama , Neoplasias Pulmonares , Tumor Filoide , Femenino , Humanos , Adulto , Tumor Filoide/diagnóstico , Tumor Filoide/cirugía , Tumor Filoide/patología , Mama/patología , Resultado del Tratamiento , Neoplasias Pulmonares/patología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patologíaRESUMEN
Shrimp aquaculture is a rapidly growing sector that makes a significant economic contribution. However, the aquaculture industry is confronted with significant challenges, and infectious diseases, notably Acute Hepatopancreatic Necrosis Disease (AHPND), have emerged as severe threat. AHPND is caused by pathogens carrying the pVA-1 plasmid, which expresses the PirAB toxin, and it has wreaked havoc in shrimp aquaculture, imposing substantial economic burdens. To address this issue, it is crucial to delve into shrimp's immune responses. Therefore, this comprehensive review offers an in-depth examination of AHPND outbreaks, encompassing various facets such as environmental factors, host susceptibility, and the mechanisms employed by the pathogens. Traditional approaches to combat AHPND, primarily relying on chemicals and antibiotics, have raised concerns related to antibiotic resistance and have demonstrated limited success in disease control. Hence this review spotlights recent advancements in molecular diagnostics, therapeutic agents, and research related to shrimp immunity. Understanding these developments is crucial in the ongoing battle against AHPND. In conclusion, this review underscores the pressing need to comprehend the underlying mechanisms of AHPND pathogenesis and emphasizes the importance of developing comprehensive and effective solutions to combat this devastating disease, which continues to threaten the sustainability of shrimp farming.
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Penaeidae , Vibrio parahaemolyticus , Animales , Vibrio parahaemolyticus/fisiología , Penaeidae/genética , Acuicultura , Enfermedad Aguda , Necrosis , Manejo de la EnfermedadRESUMEN
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in the Asian belt. These cancers show poor prognosis with an overall 5-year survival rate less than 19%. Exploring new molecular therapeutic targets such as epidermal growth factor receptor (EGFR) could be the corner stone of new curative treatment. The present study was done to analyze the overexpression of EGFR in different grades of ESCC and explore its role as a diagnostic and theranostic marker in ESCC. METHODS: In this retrospective study, 50 formalin-fixed paraffin-embedded blocks of ESCCs diagnosed from 2014 to 2019 were retrieved. The biopsies were subjected to immunohistochemistry staining of EGFR. The intensity of the membrane staining was reviewed and scored. Compared with various intrinsic and extrinsic factors using Chi-square test, scores more than 2+ were considered as overexpression. RESULTS: Majority (84%) specimens demonstrated overexpression of EGFR where high-grade ESCCs had greater overexpression rates compared to low-grade ESCC (P < 0.05). CONCLUSION: By targeting the EGFR molecules, anti-EGFR drugs could block their signals and stop the growth and spread of ESCCs especially high-grade tumors while harming the normal cells as little as possible. A clinical trial using anti-EGFR monoclonal antibodies will help in the long run to develop immunotherapy drugs.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/terapia , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Estudios Retrospectivos , Receptores ErbB/genética , Receptores ErbB/metabolismoRESUMEN
IgG4 related disease (IgG4-RD) is a fibro-inflammatory disease, with tendency to affect any organ of the body. However, few cases affecting the skull base have been reported in literature. We report one such case in an elderly male, who presented us with a mass lesion in the skull base that mimicked nasopharyngeal malignancy. On thorough clinical history, examination, and investigations, IgG4 Related disease was diagnosed and treatment was started for it. The patient responded well to the treatment and is on follow up.
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Purpose: To evaluate the accuracy of breast shear wave elastography (SWE) and p63 immunohistochemistry (IHC) in the diagnosis of indeterminate breast lesions. Methods: Based on detailed clinical examination and a combination of X-ray mammography/B-mode ultrasound with SWE, a total of 40 patients with breast lumps (BI-RADS 4) were included. Patients with previous diagnosis of breast cancer and a previous history of surgery, chemotherapy, or radiotherapy in the same breast as the present lesion were excluded. Core needle biopsy of the breast lesion was performed, and p63 IHC staining was performed. A final histopathological report of the definitive procedure was considered as the gold standard. The sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and accuracy were calculated for each modality. Results: The mean age of the patients included in the study was 50.85 ± 13.53 years. Of the 40 patients recruited, 23 were clinically malignant and 17 were benign. The sensitivity, specificity, PPV, NPV, and accuracy of SWE were 91.3%, 94.1%, 95.5%, 88.9%, and 92.5% and those of p63 IHC were 95.7%, 100%, 100%, 94.4%, and 97.5%, respectively. Overall, the parametric values were higher for p63 IHC as compared to clinical examination and elastography. The area under the ROC curve (AUC) for p63 IHC (.978) was higher than those for SWE (.927) and clinical examination (.898). Conclusion: SWE and p63 IHC are highly reliable novel modalities that demonstrate enhanced diagnostic accuracy of indeterminate breast lesions aiding in the early initiation of appropriate treatment and reducing the number of women subjected to biopsy or short-term follow-up for benign-appearing solid breast lesions.
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Diagnóstico por Imagen de Elasticidad , Humanos , Femenino , Adulto , Persona de Mediana Edad , Diagnóstico por Imagen de Elasticidad/métodos , Ultrasonografía Mamaria/métodos , Estudios Prospectivos , Inmunohistoquímica , Sensibilidad y EspecificidadRESUMEN
Mammography is considered to be the gold standard for screening and detection of breast malignancies. Among different biochemical markers used to detect carcinoma of breasts, p63 has been widely popularized for its effectiveness in the detection of myoepithelial cells which are an important indicator of breast benignity. In this study, we plan to statistically analyze and correlate the Breast Imaging Reporting and Data System (BI-RADS) 4 subcategories grading on mammogram imaging with p63 immunostaining. A total of 80 patients were taken into the study within a period of two years (2016-2018) after ensuring the inclusion and exclusion criteria. They were further sorted into different BI-RADS 4 subcategories, i.e., taking into consideration X-ray mammogram and tomosynthesis findings, 57 samples were categorized as low suspicion (BI-RADS 4A), while 12 were classified as intermediate (BI-RADS 4B), and the remaining 11 samples were categorized as highly suspicious (BI-RADS 4C). Although considered to be leaning toward malignancy, a BI-RADS reading of 4 (namely 4A-low suspicion, 4B-moderate suspicion, and 4C-high suspicion for malignancy) needs further evaluation for accurate diagnosis. There have been cases within our own observation where a lesion that is highly suspicious of malignancy has turned out to be a benign finding. Further, evaluating the expression of a p63 marker can help prevent mutilating surgeries for indeterminate lesions. The present study has been conducted to study the correlation of tomosynthesis grading of lesions that has been categorized from low-to-high suspicion, with a p63 immunostaining pattern in these lesions.
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Background: There are a wide range of diagnostic markers for colorectal cancers like detection of mutated KRAS, TP53, and APC genes. However, genetic and immunological factors have also been attributed to the cancer prognosis. The present study was carried out to evaluate the expression of CTLA-4 in colorectal cancers. Methods: This cross-sectional study was carried out among 30 resected specimens of colorectal cancer. Paraffin blocks were made on samples from tumor areas along with adjacent normal areas. Immunohistochemistry for CTLA-4 was done on the sections along with controls. Gross findings were recorded from the blocks. Blocks with section containing normal epithelium and tumor were chosen for immunohistochemistry. Results: Overexpression of CTLA-4 was observed in 43.3% of the tumors. There was a significantly high tumor infiltration among those specimens showing overexpression of CTLA-4. The observed difference was statistically significant (P < 0.05). On comparing the grade of the tumor with intensity of CTLA4 uptake, it was observed that majority of the well-differentiated tumors (66.7%) had an intensity of 1+ whereas majority of the poorly differentiated tumors had an intensity of 3+ (66.7%). Conclusion: The present study has demonstrated overexpression of CTLA-4 in colorectal cancer specimens, and also highlighted the potential scope for anti-CTLA-4 agents like Ipilimumab in cancer therapy. The need for further evaluation to examine five-year survival with such immunotherapies is essential to document candid therapeutic recommendations for colorectal cancers.
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Neoplasias del Colon , Neoplasias Colorrectales , Humanos , Antígeno CTLA-4/genética , Inmunohistoquímica , Estudios Transversales , Ipilimumab/uso terapéutico , Neoplasias del Colon/diagnóstico , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genéticaRESUMEN
INTRODUCTION: Imaging-guided breast tissue biopsy has become an acceptable alternative to open surgical biopsy for nonpalpable breast lesions. Discussion of abnormal results of the correlation between imaging and pathological findings can be very challenging as it can assist in decision-making with regard to the further treatment options by arriving at a comprehensive diagnosis. MATERIALS AND METHODS: This was a retrospective study. Radiological data from imaging-guided breast biopsies of 500 patients during a 6-year period was collected and classified by a specialist radiologist as per the BI-RADS format. Histopathology reports were studied and discordance analyzed. RESULTS: A total of 500 cases were reviewed. Approximately 33% (168) cases fell into the BI-RADS 3 category, 24.4% (122) into the BI-RADS 4, and 37% (187) into BI-RADS 5 categories. Approximately 50% (n = 250) cases were benign, 2.6% (13) belonged to the high-risk category, and 47.4% (237) were malignant. The number of discordant cases was 12 (2.4%), mostly due to technical factors. Sensitivity of biopsies to detect malignancy was 85%, specificity was 96%, and accuracy of biopsy in diagnosing cancer was 90%. DISCUSSION: The "triple assessment" is the most sensitive method for detecting early breast cancer. An effective communication pathway must be established between a clinician, radiologist, and pathologist for surgical excision in discordance as it carries a high prevalence of carcinoma in these lesions. CONCLUSION: In discordant cases, either due to abnormal results of imaging or of abnormal pathological findings, the final decision is based on two concordant findings, out of the three parameters. This involves a multidisciplinary breast conference and an active participation by the pathologist.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Mama/patología , Técnicas Histológicas/normas , Mamografía/normas , Adulto , Biopsia , Mama/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/patología , Femenino , Humanos , Mamografía/estadística & datos numéricos , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
NâGQDs with an average size of ca. 20-30 nm are utilized for the picomolar detection of inhibitory neurotransmitters, glycine (Gly), in pH ca. 7.0. The crystalline nature, morphology, elemental composition, and chemical state of N-GQDs are investigated by XRD, FE-SEM, HR-TEM, XPS, and FT-IR techniques. The addition of Gly (100 × 10-9 M; 0 â 1.0 mL) steadily quenches the fluorescence intensity of N-GQD (1 × 10-6 M) at 432 nm (λex 333 nm) due to inner filter effect (IFE) through the formation of ground-state complex, N-GQDâ¢Gly. The excitation-independent NâGQDs showed an outstanding selectivity and sensitivity towards Gly with binding constant (Ka = 8.97 × 10-3 M-1) and LoD (21.04 pM; S/N = 3). Time-correlated single-photon counting experiment confirms the static quenching of N-GQD (8.77 â 8.85 ns) in the presence of Gly. The interference of other amino acids on the strong binding of the N-GQDâ¢Gly complex in H2O is examined. Combinatorial Ex-OR and NOT gate logic circuits that could be useful in neuromorphic computing are developed based on the reversible fluorescence intensity changes of N-GQD upon the addition of Gly (ФF 0.54 â 0.39). The real-time application of N-GQD was investigated using commercially available relevant milk samples. Remarkably, not less than 99% cytotoxic reactivity of N-GQDs is attained against HeLa cells.
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Grafito , Puntos Cuánticos , Animales , Células HeLa , Humanos , Leche , Neurotransmisores , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Traditional parotidectomy incision was devised by Blair (1912) which was modified by Bailey (1941). Over the years various approaches and techniques have evolved to improve the aesthetic outcome and at the same time for complete disease clearance with reduced complications. In this study, we evaluated the feasibility of our mini-incision parotidectomy technique along with the surgical and quality of life (QOL) outcomes. This prospective case series was conducted at Apollo Hospitals, Bangalore over a period of 2 years (June 2018-August 2020) and includes 20 patients. The surgical outcomes were assessed in terms of feasibility of mini-incision technique with respect to levels of parotid involved and functional outcomes in terms of presence or absence of complications like facial palsy (temporary or permanent), seroma and Frey's syndrome. Patient related quality of life (QOL) outcomes were assessed in terms of post-operative pain score, patient comfort score and cosmetic score by using numerical rating scale-11 (NRS-11). The mini-incision parotidectomy technique is feasible for lesions in all the parotid levels and conversion or lengthening of incision was not needed in any of the cases. 2(10%) patients had temporary facial palsy (House-Brackman grade III) which was recovered within 3 weeks after surgery. One patient (5%) with adenoid cystic carcinoma had permanent facial palsy. Out of 20 patients 2(10%) had seroma and 1(5%) patient presented with Frey's syndrome. Mean post-operative pain score at 0, 6 and 24 h were 4.8, 3.4 and 1.8 out of 10 respectively. Mean comfort score was 9 out of 10 and mean cosmetic score was 9.5 out of 10. Mini-incision parotidectomy technique can render improved functional as well as aesthetic outcomes after parotidectomy without compromising the surgical clearance of the disease process.
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Facial nerve identification is considered to be a crucial step in parotid surgery as inadvertent injury to the nerve will lead to facial paralysis. Multiple landmarks are described in literature to identify the facial nerve during parotid surgery but controversies remain as the consistency and accuracy of these landmarks vary. Numerous studies exist in literature but they fail to address a single landmark that is most reliable to identify the facial nerve during parotid surgery. The purpose of this study is to find reliable landmarks for identification of the main trunk of facial nerve during parotid surgery by evidence gathered by cadaveric dissection and intraoperative study during parotid surgery and develop a systematic approach to identify the facial nerve trunk. This prospective study included 41 cadavers (82 parotid regions) and 20 patients with parotid pathology who underwent parotidectomy. We evaluated the feasibility of our C-M-S technique to identify the main trunk of facial nerve in both anatomical and surgical study. The relationship of landmarks (tragal pointer, tympanomastoid suture, superior border of posterior belly of digastric muscle) to the facial nerve trunk was assessed and the shortest distance between them from the facial trunk was measured using a slide caliper. The measurements were compared between the anatomical and surgical study. The main trunk of facial nerve was successfully identified in all cases using C-M-S technique in both anatomical and surgical study. Distance of facial nerve trunk to tragal pointer was more in the cadaveric sample (13.04 ± 5.238 mm) compared to live patients (9.95 ± 3.967 mm) with statistically significant difference (p = 0.036). The mean distance of tympanomastoid suture and posterior belly of digastric muscle to the facial nerve trunk was similar in anatomical and surgical study with p value of 0.877 and 0.083 respectively. The tympanomastoid suture, posterior belly of digastric muscle and tragal pointer are the most useful landmarks for facial nerve identification during parotid surgery. In our study we found that the tympanomastoid suture line is the most consistent landmark present in all our cases and being closest to the facial nerve trunk in both anatomical and surgical study. Further we recommend using the "C-M-S technique" in order to locate the main trunk of the facial nerve.
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Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare neoplasm with unknown etiology. It was previously referred to as Clear cell sarcoma of gastrointestinal tract. This tumor is characterized by a higher rate of local recurrence and metastasis. Due to its aggressive clinical course, distinguishing this entity from various other mimickers is very essential. Herein, we present a case of malignant GNET in a 33-year-old male patient.
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Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/patología , Tracto Gastrointestinal/patología , Tumores Neuroectodérmicos/diagnóstico , Tumores Neuroectodérmicos/patología , Adulto , Biomarcadores de Tumor , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/terapia , Humanos , Inmunohistoquímica/métodos , Hibridación Fluorescente in Situ , Masculino , Tumores Neuroectodérmicos/genética , Tumores Neuroectodérmicos/terapia , Proteína EWS de Unión a ARN/genética , Sarcoma de Células Claras/patologíaRESUMEN
Amino acids are the noteworthy entity among biological molecules with diverse properties such as zwitterionic and amphoteric. Functionalizing carbon-based quantum dots using amino acids might be used for the extreme enhancement of electronic and optical properties of quantum dots and improve the performance of the resultant amino acid-functionalized quantum dots. The amino acid-functionalized quantum dots are highly soluble, sustainable, and biocompatible with virtuous optical and electrical performance, which makes them potential and suitable candidates for fabricating optoelectronic devices. The tenacity of using amino acids as functional groups to functionalize quantum dots and their novel properties are conferred to attain their multiple applications. The goal of this review is to provide the choices of amino acids based on the desired applications and a variety of functionalization techniques to make them a noteworthy material for future applications. The method of one-step and two-step functionalization strategies along with the properties of the resultant functionalized quantum dots and their plausible applications and future scope of the material are highlighted. Amidation is the basic principle behind the functionalization of quantum dots with amino acids. This review would be an exciting prospect to explore the pathways of the possible applications in different domains, in which the amino acid-functionalized quantum dots have not yet been explored. Further, this review article helps in pitching a variety of prominent applications right from sensors to energy storage systems either using the optical property or electronic property of amino acid-functionalized quantum dots.
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The COVID-19 is an acute and contagious disease characterized by pneumonia and ARDS. The disease is caused by SARS-CoV-2, which belongs to the family of Coronaviridae along with MERS-CoV and SARS-CoV-1. The virus has the positive-sense RNA as its genome encoding for ~26 proteins that work together for the virus survival, replication, and spread in the host. The virus gets transmitted through the contact of aerosol droplets from infected persons. The pathogenesis of COVID-19 is highly complex and involves suppression of host antiviral and innate immune response, induction of oxidative stress followed by hyper inflammation described as the "cytokine storm," causing the acute lung injury, tissue fibrosis, and pneumonia. Currently, several vaccines and drugs are being evaluated for their efficacy, safety, and for determination of doses for COVID-19 and this requires considerable time for their validation. Therefore, exploring the repurposing of natural compounds may provide alternatives against COVID-19. Several nutraceuticals have a proven ability of immune-boosting, antiviral, antioxidant, anti-inflammatory effects. These include Zn, vitamin D, vitamin C, curcumin, cinnamaldehyde, probiotics, selenium, lactoferrin, quercetin, etc. Grouping some of these phytonutrients in the right combination in the form of a food supplement may help to boost the immune system, prevent virus spread, preclude the disease progression to severe stage, and further suppress the hyper inflammation providing both prophylactic and therapeutic support against COVID-19.
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Antivirales/uso terapéutico , Infecciones por Coronavirus/dietoterapia , Infecciones por Coronavirus/tratamiento farmacológico , Reposicionamiento de Medicamentos/métodos , Fitoquímicos/uso terapéutico , Neumonía Viral/dietoterapia , Neumonía Viral/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Betacoronavirus/efectos de los fármacos , COVID-19 , Infecciones por Coronavirus/patología , Síndrome de Liberación de Citoquinas/dietoterapia , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/patología , Citocinas/sangre , Suplementos Dietéticos , Humanos , Inflamación/tratamiento farmacológico , Estrés Oxidativo/fisiología , Pandemias , Neumonía Viral/patología , Probióticos/uso terapéutico , SARS-CoV-2RESUMEN
Breast cancer is the most frequently diagnosed cancer in women worldwide. Identifying reliable biomarkers and druggable molecular targets pose to be a significant quest in breast cancer research. p21-activated kinase 1 (PAK1) is a serine/threonine kinase that direct cell motility, cytoskeletal remodelling, and has been shown to function as a downstream regulator for various cancer signalling cascades that promote cell proliferation, apoptosis deregulation and hasten mitotic abnormalities, resulting in tumor formation and progression. The heterogeneity and acquired drug resistance are important factors that challenge the treatment of breast cancer. p21-activated kinase 1 signalling is crucial for activation of the Ras/RAF/MEK/ERK, PI3K/Akt/mTOR and Wnt signalling cascades which regulate cell survival, cell cycle progression, differentiation, and proliferation. A study involving proteogenomics analysis on breast cancer tissues showed the PAK1 as outlier kinase. In addition to this, few outlier molecules were identified specific to subtypes of breast cancer. A few substrates of PAK1 in breast cancer are already known. In this paper, we have discussed a similar approach called Kinase Interacting Substrate Screening (KISS) for the identification of novel oncogenic substrates of p21-activated kinase specific to subtypes of breast cancer. Such high throughput approaches are expected to accelerate the process of identifying novel drug targets and biomarkers.
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Neoplasias de la Mama/metabolismo , Quinasas p21 Activadas/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Femenino , Humanos , Transducción de Señal , Quinasas p21 Activadas/genéticaRESUMEN
OBJECTIVE: To compare the efficacy of oral paracetamol and oral ibuprofen for the management of acute headache in children with migraine without aura. METHODS: This randomized-controlled trial was done at the Pediatric department of a public hospital in India between 20 May, 2017 and 22 March, 2018, and enrolled children (aged 6-12 y) with Migraine without aura as per International Classification for Headache Disorders, 3rd edition (ICHD-3) criteria. The 50 patients (21 females, mean age 9.9 y) consecutively enrolled were randomized by block randomization to two study groups, with one group (n = 25) receiving oral paracetamol (15 mg/kg/dose) and the other group (n = 25) oral ibuprofen (10 mg/kg/dose), at home, during a single episode of acute migraine headache. The study drugs were dispensed in a blinded fashion. Pain-freedom (score of zero in a 0-10 Visual analogue pain scale) and Pain-relief (≥2-point reduction from the baseline) two-hours after the study drug intake were the primary outcomes. Side-effects to the study drugs were actively solicited. Non-parametric tests for paired data were used. RESULTS: The two groups were similar at baseline. Forty-three children (22 paracetamol group and 21 ibuprofen group) completed the study. Both pain-freedom (32% vs. 28%, P = 0.77) and pain-relief (80% vs. 80%, P = 0.86) were not significantly different between the Paracetamol and Ibuprofen groups, respectively. Ten (23.2%) children had a side-effect due to the study drug, with no significant difference between the groups (13.6% vs. 33.3%; P = 0.11). CONCLUSIONS: Both paracetamol and ibuprofen are effective and safe for the treatment of acute migraine attacks in children.