RESUMO
Cervical cancer is among the leading causes of cancer-associated mortality in women. In spite of vaccine availability, improved screening procedures, and chemoradiation therapy, cervical cancer remains the most commonly diagnosed cancer in 23 countries and the leading cause of cancer deaths in 36 countries. There is, therefore, a need to come up with novel diagnostic and therapeutic targets. Long non-coding RNAs (lncRNAs) play a remarkable role in genome regulation and contribute significantly to several developmental and disease pathways. The deregulation of lncRNAs is often observed in cancer patients, where they are shown to affect multiple cellular processes, including cell cycle, apoptosis, angiogenesis, and invasion. Many lncRNAs are found to be involved in the pathogenesis as well as progression of cervical cancer and have shown potency to track metastatic events. This review provides an overview of lncRNA mediated regulation of cervical carcinogenesis and highlights their potential as diagnostic and prognostic biomarkers as well as therapeutic targets for cervical cancer. In addition, it also discusses the challenges associated with the clinical implication of lncRNAs in cervical cancer.
Assuntos
RNA Longo não Codificante , Neoplasias do Colo do Útero , Humanos , Feminino , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Apoptose/genética , Carcinogênese/genéticaRESUMO
Spirulina is a blue-green alga, grown in alkaline water and used for detoxification of several toxic metal ions. Apart from its nutritional value, it is also used for the decontamination of toxic metal ions. Therefore, present study was envisaged to evaluate the adsorption and removal efficiency of Spirulina powder for mercury. The adsorption efficiency of Spirulina was evaluated in terms of weight of adsorbent, contact time, simulated gastric (SGF) and intestinal (SIF) fluid, and mercury concentration. In vivo removal efficacy of Spirulina for mercury was evaluated in mice. The mercury content in major tissues, urine and feces was estimated. The whole tissue retention and excretion of mercury after treatment with Spirulina were taken as a measure of its metal ions removal efficacy. Activated charcoal was taken as a standard adsorbent for comparative study. The maximum adsorption capacity of Spirulina and charcoal for mercury was found to be 66.667 and 158.730 mg g-1 in water, 83.33 and 94.340 mg g-1 in SGF and 125.0 and 133.33 mg g-1 in SIF, respectively. In mice, Spirulina and activated charcoal were significantly reduced the mercury deposition in tissues and facilitated their excretion through feces. Spirulina has shown good adsorption and removal efficacy like activated charcoal. Therefore, Spirulina can be used as a potential adsorbent to remove mercury from the body.
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Mercúrio , Spirulina , Poluentes Químicos da Água , Adsorção , Animais , Carvão Vegetal , Concentração de Íons de Hidrogênio , Íons , Cinética , Camundongos , Pós , Termodinâmica , ÁguaRESUMO
Chlorella is a green alga consumed as dietary food supplement in pulverized form. In addition to its high nutritional value, it is reported as an excellent detoxifying agent. The pulverized Chlorella is partially soluble in water and insoluble portion has been reported for removal of mercury, cadmium and radioactive strontium from body. Chlorella contains a variety of metal-binding functional groups such as carboxyl, amino, phosphoryl, hydroxyl and carbonyl groups, which has high affinity towards various metal ions. The present study was envisaged to evaluate the chelating effect of water soluble fraction of Chlorella powder (AqCH) on metal ions. Fura-2 fluorescence ratio (F340/F380) was measured by fluorescence spectrometer (FS) after the exposure of chloride salt of metals viz., strontium, cobalt, barium, cesium, thallium and mercury to lymphocytes. Pretreatment of AqCH (0.1-20 mg mL-1) was given to evaluate the attenuating effect on fura-2 fluorescence ratio induced by metal ions. The intracellular levels of these metal ions were analyzed by atomic absorption spectrophotometer (AAS) and fluorescence microscopy (FM). Pretreatment with AqCH significantly attenuated the metal induced fluorescence ratio in dose-dependent manner. The results of AAS and FM were found in coherence with fura-2 fluorescence ratio which emphasized that AqCH significantly prevented the metal ions internalization. The present study suggests AqCH chelates with these metal ions and prevents its interaction with cells thereby reducing the intracellular mobilization of Ca2+.
Assuntos
Quelantes/farmacologia , Chlorella/química , Fura-2/farmacologia , Linfócitos/efeitos dos fármacos , Metais Pesados/farmacologia , Células Cultivadas , Quelantes/química , Fura-2/química , Humanos , Metais Pesados/química , Pós/químicaRESUMO
We present a novel approach of designing and fabricating a noninvasive drug delivery device which is capable of delivering the drug to the target site in a controlled manner. The device utilizes a reservoir which can be reused once the drug has completely diffused from it. This micro-reservoir based fabricated device has been successfully tested using niosomes of insulin drug filled in, which was then sealed with a magnetic membrane of 20 µm thick and was actuated by applying magnetic field. The deflection of the membrane on application of magnetic field results in the drug release from the reservoir. The discharge of the drug solution and the release rates was controlled by external magnetic field. The simulation of the membrane deflection using COMSOL software was carried out to optimize the concentration of the ferrous nanopowder in PDMS matrix. The characterization of the devices was implemented in-vitro on water and in-vivo on Wistar rats. It was also validated using high-performance liquid chromatography (HPLC) by observing characteristic peak of insulin. The blood samples showed the retention time of 2.79 min at λmax of 280 nm which further authenticated the effectiveness of the proposed work. This noninvasive fabricated device provides reusability, precise control and can enable the patient or a physician to actively administrate the drug when required.
Assuntos
Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Animais , Preparações de Ação Retardada/química , Liberação Controlada de Fármacos/efeitos dos fármacos , Desenho de Equipamento/instrumentação , Desenho de Equipamento/métodos , Magnetismo/métodos , Masculino , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/química , Ratos , Ratos WistarRESUMO
BACKGROUND: Regardless of the most recent inclusion of mold-active agents (isavuconazole and posaconazole) to antifungal agents against mucormycosis, in conjunction with amphotericin B (AMB) items, numerous uncertainties still exist regarding the treatment of this rare infection. The order Mucorales contains a variety of fungi that cause the serious but uncommon fungal illness known as mucormycosis. The moulds are prevalent in nature and typically do not pose significant risks to people. Immunocompromised people are affected by it. OBJECTIVE: This article's primary goal is to highlight the integral role that AMB plays in this condition. METHODS: Like sinusitis (including pansinusitis, rhino-orbital, or rhino-cerebral sinusitis) is one of the many signs and symptoms of mucormycosis. The National Center for Biotechnology Information (NCBI) produces a variety of online information resources for review articles on the topic-based mucormycosis, AMB, diagnosis of mucormycosis and the PubMed® database of citations and abstracts published in life science journals. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov. RESULTS: The article provides a summary of the pharmacological attributes of the various AMB compositions accessible for systemic use. CONCLUSION: The article demonstrates the traits of the drug associated with its chemical, pharmacokinetics, stability, and other features, and illustrates their most useful characteristics for clinical application.
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Mucorales , Mucormicose , Sinusite , Humanos , Anfotericina B/uso terapêutico , Mucormicose/tratamento farmacológico , Mucormicose/diagnóstico , Mucormicose/microbiologia , Antifúngicos/uso terapêutico , Sinusite/tratamento farmacológicoRESUMO
Glioblastoma multiforme (GBM) is regarded as a highly aggressive brain cancer with a poor prognosis. There is an increase in the expression of P-glycoprotein (P-gp), responsible for multidrug resistance (MDR), making it a potential target for improving drug responses. Additionally, glioblastoma stem cells (GSCs) increase resistance to chemo- and radiotherapy and play a major role in cancer relapse. In this study, we targeted P-gp using a small molecule inhibitor, reversan (RV), to inhibit MDR that prolonged the retention of drugs in the cytosolic milieu. To eliminate GBM and GSCs, we have used two well-established anti-cancer drugs, regorafenib (RF) and curcumin (CMN). To improve the pharmacokinetics and decrease systemic delivery of drugs, we developed nanostructure hybrid lipid capsules (nHLCs), where hydrophobic drugs can be loaded in the core, and their physicochemical properties were determined by dynamic light scattering (DLS) and cryo-scanning electron microscopy (SEM). Inhibition of MDR by RV has also shown enhanced retention of nHLC in GBM cells. Co-delivery of drug-loaded nHLCs, pre-treated with RV, exhibited superior cytotoxicity in both GBM and GSCs than their individual doses and effectively reduced the size and stemness of tumor spheres and accelerated the rate of apoptosis, suggesting a promising treatment for glioblastoma.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Células-Tronco Neoplásicas , Resistência a Múltiplos Medicamentos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Lipídeos , Linhagem Celular TumoralRESUMO
Caesarean scar ectopic pregnancy (CSEP) is a uncommon presentation of pregnancy with incidence of nearly 1 in 2000 pregnancies. We present this case series of scar pregnancy with a objective to help obstetricians in early diagnosis and appropriate management to prevent its catastrophic complications.
Assuntos
Metotrexato , Gravidez Ectópica , Gravidez , Feminino , Humanos , Cicatriz/complicações , Cesárea/efeitos adversos , Gravidez Ectópica/diagnóstico , Gravidez Ectópica/etiologia , Gravidez Ectópica/cirurgiaRESUMO
Parkinson's is a progressive neurodegenerative disease of the nervous system. It has no cure, but its symptoms can be managed by supplying dopamine artificially to the brain.This work aims to engineer tricompartmental polymeric microcarriers by electrohydrodynamic cojetting technique to encapsulate three PD (Parkinson's disease) drugs incorporated with high encapsulation efficiency (â¼100%) in a single carrier at a fixed drug ratio of 4:1:8 (Levodopa (LD): Carbidopa(CD): Entacapone (ENT)). Upon oral administration, the drug ratio needs to be maintained during subsequent release from microparticles to enhance the bioavailability of primary drug LD. This presents a notable challenge, as the three drugs vary in their aqueous solubility (LD > CD > ENT). The equilibrium of therapeutic release was achieved using a combination of FDA-approved polymers (PLA, PLGA, PCL, and PEG) and the disc shape of particles. In vitro studies demonstrated the simultaneous release of all the three therapeutics in a sustained and controlled manner. Additionally, pharmacodynamics and pharmacokinetics studies in Parkinson's disease rats induced by rotenone showed a remarkable improvement in PD conditions for the microparticles-fed rats, thereby showing a great promise toward efficient management of PD.
Assuntos
Carbidopa , Catecóis , Preparações de Ação Retardada , Portadores de Fármacos , Levodopa , Doença de Parkinson , Carbidopa/farmacocinética , Carbidopa/administração & dosagem , Carbidopa/uso terapêutico , Carbidopa/farmacologia , Animais , Levodopa/farmacocinética , Levodopa/administração & dosagem , Levodopa/uso terapêutico , Levodopa/farmacologia , Doença de Parkinson/tratamento farmacológico , Preparações de Ação Retardada/química , Catecóis/química , Catecóis/uso terapêutico , Catecóis/farmacologia , Catecóis/farmacocinética , Portadores de Fármacos/química , Ratos , Masculino , Nitrilas/farmacocinética , Nitrilas/uso terapêutico , Nitrilas/farmacologia , Antiparkinsonianos/farmacocinética , Antiparkinsonianos/uso terapêutico , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/farmacologia , Liberação Controlada de Fármacos , Ratos Sprague-Dawley , Rotenona/farmacologiaRESUMO
A cross-sectional study was done to assess the degree of current awareness and behaviors about cervical cancer among females in urban and rural areas of North India. This survey was conducted on one thousand females (500 rural and 500 urban). A well-structured questionnaire was designed to collect information about participants' knowledge on cancer of cervix uteri such as age, height and weight measurements, marital status, menstrual status, personal hygiene, age at menarche, sexual history, pregnancy and abortion history, use of contraceptive pills for birth-control, smoking, alcohol consumption, and other relevant information. The data was collected by conducting face-to-face interviews after obtaining the verbal consent of the participants. The data has the potential to reduce disease burden by spreading awareness about symptoms and risk factors of cervical cancer as well as implementation of effective early screening strategies.
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PURPOSE: Hysterosalpingography (HSG) is an important tool for evaluation of tubal factors in infertility. It does not require anesthesia but can be a painful procedure. Thus, this study was undertaken to establish the role of intracervical block as pain relief modality for HSG. METHODS: This prospective, randomized study included hundred women attending the Department of Obstetrics and Gynecology, at a tertiary care centre in India. They were divided randomly through a computer generated table into two groups of 50 women each. In the study group, women received intracervical block along with premedication whereas in the control group women received premedication alone. Each patient was asked to rate her pain at six different points of time (T1-T6) during HSG using Visual analogue scale (VAS) and Verbal descriptive score. The difference in pain scores amongst the two groups was analyzed using independent t test. RESULTS: Reduction of pain was observed from placement of tenaculum till end of procedure (T3-T6) with intracervical block (p < 0.05). Pain remained at a statistically lower level during the most painful steps i.e. traction of the cervix (VAS: 2.080.49 cm, 95 % C I 1.18-2.98 vs. 4.21.15 cm, 95 % CI 3.3-5.1, p = 0.001) and with the insertion of dye (VAS: 2.640.49, 95 % CI 1.7-3.5 vs. 5.121.45. 95 % CI 4.3-6.0, p = 0.001) in the study group as compared to control group. CONCLUSION: Intracervical block can be offered to all women undergoing HSG to make the procedure less painful and thus improve the compliance.
Assuntos
Analgesia/métodos , Histerossalpingografia/efeitos adversos , Manejo da Dor/métodos , Adulto , Analgésicos/administração & dosagem , Anestésicos Locais , Colo do Útero/efeitos dos fármacos , Testes de Obstrução das Tubas Uterinas , Feminino , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/etiologia , Lidocaína/administração & dosagem , Dor , Medição da Dor , Pré-Medicação , Estudos ProspectivosRESUMO
Flurbiprofen is used in the treatment of arthritis. However, its multiple dosing due to short elimination half life is a concern for such treatment. This work aims to develop nanostructured lipid carriers (NLCs) of flurbiprofen and evaluate their potential for transdermal delivery. The NLCs were prepared by the optimized o/w emulsification-homogenization-sonication technique using coconut oil (liquid lipid). The NLCs were found to be spherical with uniform size (214 nm). The entrapment efficiency and zeta potential were 92.58% and -30.70 mV, respectively. Differential scanning calorimetry (DSC) showed the amorphous state of flurbiprofen encapsulated in NLCs. The percentage cumulative drug release through the excised rat skin from NLCs was biphasic and significantly prolonged compared with the commercial gel. DSC of the treated skin indicated that the NLCs penetrate into follicles of the skin and accumulate in the dermis. The bioavailability of flurbiprofen from NLCs was more than 1.7-fold that of the commercial gel. The NLCs showed a quick onset and sustained anti-inflammatory effect over period of 24 h for carrageenan-induced rat paw edema than the commercial gel. The stability data revealed that the NLCs were more stable when stored at 5°C. In conclusion, prepared NLCs have potential for skin targeting and sustained drug release.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Portadores de Fármacos , Flurbiprofeno/administração & dosagem , Lipídeos/química , Nanoestruturas/administração & dosagem , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Emulsões , Flurbiprofeno/farmacocinética , Masculino , Tamanho da Partícula , Ratos , Ratos Wistar , Pele/metabolismoRESUMO
Magnetic nanoparticle (MNP) delivery systems are promising for targeted drug delivery, imaging, and chemo-hyperthermia of cancer; however, their uses remain limited primarily due to their toxicity associated with reactive oxygen species (ROS) generation, targeted delivery, and biodegradation. Attempts employing polymer coatings to minimize the toxicity, along with other challenges, have had limited success. We designed a novel yet generic 'one-for-all' polypropylene sulphide (PPS) coated magnetic nano-delivery system (80 ± 15 nm) as a multi-faceted approach for significant biocompatibility improvement, loading of multiple drugs, ROS-responsive delivery, and combined chemo-hyperthermia therapy for biomedical applications. Three distinct MNP systems (15 ± 1 nm) were fabricated, coated with PPS polymer, and investigated to validate our hypothesis and design. Simultaneous degradation of MNPs and PPS coatings with ROS-scavenging characteristics boosted the biocompatibility of MNPs 2-3 times towards non-cancerous fibroblasts (NIH3T3) and human epithelial cells (HEK293). In an alternating magnetic field, PPS-MNPs (MnFe) had the strongest heating characteristics (SAR value of 240 W g-1). PPS-MNP drug-loaded NPs were efficiently internalised into cells and released 80% of the drugs under tumor microenvironment-mimicking (pH 5-7, ROS) conditions, and demonstrated effective chemo-hyperthermia (45 °C) application for breast cancer cells with 95% cell death in combined treatment vs. 55% and 30% cell death in only hyperthermia and chemotherapy respectively.
Assuntos
Hipertermia Induzida , Nanopartículas de Magnetita , Nanopartículas , Neoplasias , Animais , Camundongos , Humanos , Polipropilenos/farmacologia , Nanopartículas de Magnetita/uso terapêutico , Espécies Reativas de Oxigênio , Células HEK293 , Células NIH 3T3 , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Hipertermia Induzida/métodos , Fenômenos Magnéticos , Microambiente TumoralRESUMO
OBJECTIVE: To compare the efficacy of propranolol prophylaxis with placebo on headache frequency in children with migraine over the 3-mo follow-up. METHODS: In this randomized, double-blind, placebo-controlled trial children aged 6-12 y with newly diagnosed migraine without aura as per the International Classification for Headache Disorders, 3rd edition (ICHD-3) criteria were enroled. They were randomized to the intervention group receiving oral propranolol (1-3 mg/kg/d, BID) and the control group receiving a similar looking, inert, oral placebo for migraine prophylaxis for 3 mo. The number of migraine attacks over the 3-mo follow-up (using a headache diary) was the primary outcome. Pediatric Migraine Disability Assessment Scale (PedMIDAS) was used for assessing disability and Visual analogue scale was used for assessing headache severity. Analysis was done on intention-to-treat basis. RESULTS: Twenty children (10 in each group) completed the study. The two groups were similar at baseline. Both the study drugs produced significant reduction of headache frequency after the study intervention (p = 0.002). However, there was no difference between the two groups with respect to either the median (IQR) number of headache attacks [22 (20, 25) vs. 14 (10, 20); p = 0.05], headache severity [1 (0, 1) vs. 0.5 (0, 1); p = 0.48] or migraine disability [39.5 (28, 44) vs. 35 (22, 38); p = 0.27]. Adverse effects were higher in the intervention group (p = 0.52). CONCLUSIONS: Propranolol was effective for migraine prophylaxis in children but the effect was not higher than placebo. Larger placebo-controlled trials of propranolol need to be conducted to decide its place in migraine prophylaxis in children. TRIAL REGISTRATION: Thailand Clinical Trials Registry; TCTR20200621001.
Assuntos
Enxaqueca sem Aura , Propranolol , Humanos , Criança , Propranolol/uso terapêutico , Enxaqueca sem Aura/tratamento farmacológico , Enxaqueca sem Aura/prevenção & controle , Cefaleia , Medição da Dor , Método Duplo-Cego , Resultado do TratamentoRESUMO
Cancer stem cells (CSCs) present a formidable challenge in cancer treatment due to their inherent resistance to chemotherapy, primarily driven by the overexpression of ABC transporters and multidrug resistance (MDR). Despite extensive research on pharmacological small-molecule inhibitors, effectively managing MDR and improving chemotherapeutic outcomes remain elusive. On the other hand, magnetic hyperthermia (MHT) holds great promise as a cancer therapeutic, but there is limited research on its potential to reverse MDR in breast CSCs and effectively eliminate CSCs through combined chemo-hyperthermia. To address these gaps, we developed tumor microenvironment-sensitive, drug-loaded poly(propylene sulfide) (PPS)-coated magnetic nanoparticles (PPS-MnFe). These nanoparticles were employed to investigate hyperthermia sensitivity and MDR reversion in breast CSCs, comparing their performance to that of small-molecule inhibitors. Additionally, we explored the efficacy of combined chemo-hyperthermia in killing CSCs. CSC-enriched breast cancer cells were subjected to low-dose MHT at 42 °C for 30 min and then treated with the chemical MDR inhibitor salinomycin (SAL). The effectiveness of each treatment in inhibiting MDR was assessed by measuring the efflux of the MDR substrate, rhodamine 123 (R123) dye. Notably, MHT induced a prolonged reversal of MDR activity compared with SAL treatment alone. After successfully inhibiting MDR, the breast CSCs were exposed to chemotherapy using paclitaxel to trigger synergistic cell death. The combination of MHT and chemotherapy demonstrated remarkable reductions in stemness properties, MDR reversal, and the effective eradication of breast CSCs in this innovative dual-modality approach.
Assuntos
Neoplasias da Mama , Hipertermia Induzida , Humanos , Feminino , Polipropilenos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Resistência a Múltiplos Medicamentos , Células-Tronco Neoplásicas/patologia , Concentração de Íons de Hidrogênio , Fenômenos Magnéticos , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Management of uncontrolled bleeding due to traumatic injuries occurring in battlefields and road traffic accidents is a major healthcare concern, especially in developing countries like India. Since natural coagulation mechanism alone is insufficient to achieve haemostasis quickly in such cases, application of an external haemostatic product is generally required to accelerate the coagulation process. We had recently reported preliminary comparison of four natural absorbent gums, which indicated towards haemostatic potential of gum tragacanth (GT) and xanthan gum (XG). Present study involves fabrication of haemostatic dressings incorporated with different concentrations of GT or XG, along with ciprofloxacin (a broad-spectrum antibiotic) and other excipients over woven cotton gauze. Prepared gauzes were investigated for physico-chemical characteristics, in-vitro blood interaction studies, antibacterial effect and in-vivo haemostatic efficacy in Sprague Dawley rats using two bleeding models. Acute dermal toxicity studies were also carried out as per OECD guidelines. SEM studies showed that gauzes coated with XG had thin, uniform layer of coating, while in case of GT; coating was comparatively rough with insoluble particles of GT adhering over gauze surface, forming voids on the fibers. Coated gauzes exhibited optimum mechanical properties in terms of tensile strength and percent extension at break. GT coated dressings showed good fluid uptake and retention ability in-vitro. Test gauzes were non-hemolytic in nature, did not elicit any dermal toxicity on animals' skin and had the ability to protect against E. coli infection. In-vivo efficacy studies in rat femoral artery and liver laceration bleeding models indicated that gauzes coated with 4% GT were able to clot blood in least time (36.67 ± 3.33s and 40 ± 2.58s respectively) as compared to other gum combinations and commercially available dressing 'Surgispon® (103.3 ± 4.22s and 85 ± 5.62s respectively). Results of this study validate our initial findings of the potential of gum tragacanth to be developed into a suitable haemostatic product.
Assuntos
Hemostáticos , Tragacanto , Ratos , Animais , Tragacanto/química , Escherichia coli , Ratos Sprague-Dawley , Hemostáticos/farmacologia , Hemostáticos/uso terapêutico , Hemorragia/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , BandagensRESUMO
Cervical agenesis or dysgenesis is a rare Mullerian anomaly that is usually associated with vaginal aplasia. A literature review revealed reports of 83 cases including ours, of which 57 (68.6%) presented with obstruction of the external OS, 11 (13.2%) had the cervix replaced by a fibrous cord and 5 (6.02%) had a fragmented cervix. A total of 24 (28.9%) were managed by core and drilling technique (CDT), 16(19.2%) patients underwent uterovaginal anastomosis (UVA), 7(8.4%) underwent total abdominal hysterectomy preserving the ovaries and 5 (6.02%) were managed by cervical reconstruction. Unfortunately, 31 failed to return after their clinical and radiological diagnosis was confirmed. Early diagnosis and treatment are necessary to avoid long-term complications.
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Procedimentos de Cirurgia Plástica , Anormalidades Urogenitais , Feminino , Humanos , Colo do Útero/diagnóstico por imagem , Colo do Útero/cirurgia , Útero/diagnóstico por imagem , Útero/cirurgia , Histerectomia , Anormalidades Urogenitais/cirurgiaRESUMO
Immunotherapy involves the therapeutic alteration of the patient's immune system to identify, target, and eliminate cancer cells. Dendritic cells, macrophages, myeloid-derived suppressor cells, and regulatory T cells make up the tumor microenvironment. In cancer, these immune components (in association with some non-immune cell populations like cancer-associated fibroblasts) are directly altered at a cellular level. By dominating immune cells with molecular cross-talk, cancer cells can proliferate unchecked. Current clinical immunotherapy strategies are limited to conventional adoptive cell therapy or immune checkpoint blockade. Targeting and modulating key immune components presents an effective opportunity. Immunostimulatory drugs are a research hotspot, but their poor pharmacokinetics, low tumor accumulation, and non-specific systemic toxicity limit their use. This review describes the cutting-edge research undertaken in the field of nanotechnology and material science to develop biomaterials-based platforms as effective immunotherapeutics. Various biomaterial types (polymer-based, lipid-based, carbon-based, cell-derived, etc.) and functionalization methodologies for modulating tumor-associated immune/non-immune cells are explored. Additionally, emphasis has been laid on discussing how these platforms can be used against cancer stem cells, a fundamental contributor to chemoresistance, tumor relapse/metastasis, and failure of immunotherapy. Overall, this comprehensive review strives to provide up-to-date information to an audience working at the juncture of biomaterials and cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Cancer immunotherapy possesses incredible potential and has successfully transitioned into a clinically lucrative alternative to conventional anti-cancer therapies. With new immunotherapeutics getting rapid clinical approval, fundamental problems associated with the dynamic nature of the immune system (like limited clinical response rates and autoimmunity-related adverse effects) have remained unanswered. In this context, treatment approaches that focus on modulating the compromised immune components within the tumor microenvironment have garnered significant attention amongst the scientific community. This review aims to provide a critical discussion on how various biomaterials (polymer-based, lipid-based, carbon-based, cell-derived, etc.) can be employed along with immunostimulatory agents to design innovative platforms for selective immunotherapy directed against cancer and cancer stem cells.
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Materiais Biocompatíveis , Neoplasias , Humanos , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Neoplasias/patologia , Imunoterapia/métodos , Células-Tronco Neoplásicas/patologia , Lipídeos , Microambiente TumoralRESUMO
The continuous implementation of Artificial Intelligence (AI) in multiple scientific domains and the rapid advancement in computer software and hardware, along with other parameters, have rapidly fuelled this development. The technology can contribute effectively in solving many challenges and constraints in the traditional development of the drug. Traditionally, large-scale chemical libraries are screened to find one promising medicine. In recent years, more reasonable structure-based drug design approaches have avoided the first screening phases while still requiring chemists to design, synthesize, and test a wide range of compounds to produce possible novel medications. The process of turning a promising chemical into a medicinal candidate can be expensive and time-consuming. Additionally, a new medication candidate may still fail in clinical trials even after demonstrating promise in laboratory research. In fact, less than 10% of medication candidates that undergo Phase I trials really reach the market. As a consequence, the unmatched data processing power of AI systems may expedite and enhance the drug development process in four different ways: by opening up links to novel biological systems, superior or distinctive chemistry, greater success rates, and faster and less expensive innovation trials. Since these technologies may be used to address a variety of discovery scenarios and biological targets, it is essential to comprehend and distinguish between use cases. As a result, we have emphasized how AI may be used in a variety of areas of the pharmaceutical sciences, including in-depth opportunities for drug research and development.
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Inteligência Artificial , Descoberta de Drogas , Desenho de Fármacos , Software , ComputadoresRESUMO
With the increasing dependence on fluorescence bioimaging, luminogens with aggregation-induced emission (AIE) properties have gained significant attention due to their excellent photostabilization, minimal photobleaching, high reliability, and superior biocompatibility. Since mitochondria are crucial subcellular organelles in eukaryotic cells with important biological functions, organelle-specific AIE emitters with distinct functions have been highly sought after, but with limited success using simple synthetic methods. Here, we describe a strategy for synthesizing two triphenylamine (TPA) based acrylonitriles, tethered to different donor groups, TPA and phenothiazine (PTZ), respectively, with superior AIE properties using Suzuki coupling. We conducted a systematic and detailed experimental analysis of the structural characteristics of both AIE luminogens, which exhibited excellent photostability, a large Stokes shift, and bright solid-state emission. A cell viability study carried out with F1 and F2 dyes revealed that both luminogens exhibited excellent biocompatibility. Based on fluorescence experiments, F2 displayed excellent AIE characteristics, permeability, biocompatibility, and photostability compared to rhodamine 123, allowing it to selectively stain and track mitochondria in cancer cells over an extended period of time. The Pearson correlation coefficient of F2 and rhodamine 123 was estimated to have an r-value of 0.99. Our findings are expected to provide insight into the synthesis of an extensive archive of AIE-based acrylonitriles with fascinating properties for mitochondrial staining.
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Corantes Fluorescentes , Mitocôndrias , Humanos , Rodamina 123 , Reprodutibilidade dos Testes , Corantes Fluorescentes/química , Células HeLaRESUMO
Choriocarcinoma of ovary is a rare aggressive tumor of ovary. It may be gestational or nongestational tumor. High index of suspicion is required for diagnosis in reproductive age group females. Here, we present a case report of a 30-year-old female who was operated for ectopic pregnancy but was diagnosed as ovarian choriocarcinoma on histopathology. The patient had abnormally high beta-human chorionic gonadotropin levels with history of amenorrhea and negative urine pregnancy test. On laparotomy, a mass of 8 cm × 10 cm was found which was confirmed as choriocarcinoma on histopathological examination. The patient was managed with chemotherapy and responded well to treatment.