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Mitochondrial (MITO) dysfunction occurs in the failing heart and contributes to worsening of heart failure (HF). Reduced aldehyde dehydrogenase 2 (ALDH2) in left ventricular (LV) myocardium of diabetic hearts has been implicated in MITO dysfunction through accumulation of toxic aldehydes including and elevated levels of 4-hydroxy-2-nonenal (4HNE). This study examined whether dysregulation of MITO ALDH2 (mALDH2) occurs in mitochondria of the failing LV and is associated with increased levels of 4HNE. LV tissue from 7 HF and 7 normal (NL) dogs was obtained. Protein quantification of total mitochondrial ALDH2 (t-mALDH2), phosphorylated mALDH2 (p-mALDH2), total MITO protein kinase c epsilon (t-mPKCε), phosphorylated mPKCε (p-mPKCε) was performed by Western blotting, and total mALDH2 enzymatic activity was measured. Protein adducts of 4HNE-MITO and 4HNE-mALDH2 were also measured in MITO fraction by Western Blotting. Protein level of t-mALDH2 was decreased in HF compared with NL dogs (0.63 ± 0.07 vs 1.17 ± 0.08, p < 0.05) as did mALDH2 enzymatic activity (51.39 ± 3 vs. 107.66 ± 4 nmol NADH/min/mg, p < 0.05). Phosphorylated-mALDH2 and p-mPKCε were unchanged. 4HNE-MITO proteins adduct levels increased in HF compared with NL (2.45 ± 0.08 vs 1.30 ± 0.03 du, p < 0.05) as did adduct levels of 4HNE-mALDH2 (1.60 ± 0.20 vs 0.39 ± 0.08, p < 0.05). In isolated failing cardiomyocytes (CM) exposure to 4HNE decreased mALDH2 activity, increased ROS and 4HNE-ALDH2 adducts, and worsened MITO function. Stimulation of mALDH2 activity with ALDA-1 in isolated HF CMs compared to NL CMs improved ADP-stimulated respiration and maximal ATP synthesis to a greater extant (+47 % and +89 %, respectively). Down-regulation of mALDH2 protein levels and activity occurs in HF and contributes to MITO dysfunction and is likely caused by accumulation of 4HNE-mALDH2 adduct. Increasing mALDH2 activity (via ALDA-1) improved MITO function in failing CMs.
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The emergence of highly infectious pathogens with their potential for triggering global pandemics necessitate the development of effective treatment strategies, including broad-spectrum antiviral therapies to safeguard human health. This study investigates the antiviral activity of emetine, dehydroemetine (DHE), and congeneric compounds against SARS-CoV-2 and HCoV-OC43, and evaluates their impact on the host cell. Concurrently, we assess the potential cardiotoxicity of these ipecac alkaloids. Significantly, our data reveal that emetine and the (-)-R,S isomer of 2,3-dehydroemetine (designated in this paper as DHE4) reduce viral growth at nanomolar concentrations (i.e., IC50 â¼ 50-100 nM), paralleling those required for inhibition of protein synthesis, while calcium channel blocking activity occurs at elevated concentrations (i.e., IC50 â¼ 40-60 µM). Our findings suggest that the antiviral mechanisms primarily involve disruption of host cell protein synthesis and is demonstrably stereoisomer specific. The prospect of a therapeutic window in which emetine or DHE4 inhibit viral propagation without cardiotoxicity renders these alkaloids viable candidates in strategies worthy of clinical investigation.
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Alcaloides , Emetina , Emetina/análogos & derivados , Humanos , Emetina/farmacología , Ipeca/farmacología , Cardiotoxicidad , Antivirales/toxicidadAsunto(s)
Exosomas , Nanopartículas , Neoplasias , Humanos , Línea Celular Tumoral , Neoplasias/tratamiento farmacológicoRESUMEN
Despite its introduction more than three decades ago, gene therapy has fallen short of its expected potential for the treatment of a broad spectrum of diseases and continues to lack widespread clinical use. The fundamental limitation in clinical translatability of this therapeutic modality has always been an effective delivery system that circumvents degradation of the therapeutic nucleic acids, ensuring they reach the intended disease target. Plasmid DNA (pDNA) for the purpose of introducing exogenous genes presents an additional challenge due to its size and potential immunogenicity. Current pDNA methods include naked pDNA accompanied by electroporation or ultrasound, liposomes, other nanoparticles, and cell-penetrating peptides, to name a few. While the topic of numerous reviews, each of these methods has its own unique set of limitations, side effects, and efficacy concerns. In this review, we highlight emerging uses of exosomes for the delivery of pDNA for gene therapy. We specifically focus on bovine milk and colostrum-derived exosomes as a nano-delivery "platform". Milk/colostrum represents an abundant, scalable, and cost-effective natural source of exosomes that can be loaded with nucleic acids for targeted delivery to a variety of tissue types in the body. These nanoparticles can be functionalized and loaded with pDNA for the exogenous expression of genes to target a wide variety of disease phenotypes, overcoming many of the limitations of current gene therapy delivery techniques.
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Cancer has recently surpassed heart disease as the leading cause of deaths worldwide for the age group 45-65 and has been the primary focus for biomedical researchers. Presently, the drugs involved in the first-line cancer therapy are raising concerns due to high toxicity and lack of selectivity to cancer cells. There has been a significant increase in research with innovative nano formulations to entrap the therapeutic payload to enhance efficacy and eliminate or minimize toxic effects. Lipid-based carriers stand out due to their unique structural properties and biocompatible nature. The two main leaders of lipid-based drug carriers: long known liposomes and comparatively new exosomes have been well-researched. The similarity between the two lipid-based carriers is the vesicular structure with the core's capability to carry the payload. While liposomes utilize chemically derived and altered phospholipid components, the exosomes are naturally occurring vesicles with inherent lipids, proteins, and nucleic acids. More recently, researchers have focused on developing hybrid exosomes by fusing liposomes and exosomes. Combining these two types of vesicles may offer some advantages such as high drug loading, targeted cellular uptake, biocompatibility, controlled release, stability in harsh conditions and low immunogenicity.
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Exosomas , Neoplasias , Humanos , Liposomas/química , Exosomas/metabolismo , Portadores de Fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Fosfolípidos/metabolismo , Sistemas de Liberación de MedicamentosRESUMEN
The receptor of Advanced Glycation Endproducts (RAGE) and Advanced Glycation Endproducts (AGE) have multiple functions in our body and their restraint are being observed in neurodegenerative and memory impairment disorders. The review of different pathways allows an understanding of the probable mechanism of neurodegeneration and memory impairment involving RAGE and AGE. Commonly we observe AGE accumulation in neural cells and tissues but the extent of accumulation increases with the presence of memory impairment disorder. The presence of AGEs can also be seen in morbid accumulation, pathological structures in the form of amyloid clots, and nervous fibrillary tangles in Alzheimer's Disease (AD) and memory impairment disease.Many neuropathological and biochemical aspects of AD are explained by AGEs, including widespread protein crosslinking, glial activation of oxidative stress, and neuronal cell death. Oxidative stress is due to different reasons and glycation end products set in motion and form or define various actions which are normally due to AGE changes in a pathogenic cascade. By regulating the transit of ß-amyloid in and out of the brain or altering inflammatory pathways, AGE and it's ensnare receptor such as soluble RAGE may function as blockage or shield AD development. RAGE activates the transcription-controlling factor Necrosis Factor (NF-κB) and increases the protraction of cytokines, like a higher number of Tumor Necrosis Factor (TNF-α) and Interleukin (IL-I) by inducing several signal transduction cascades. Furthermore, binding to RAGE can pro-activate reactive oxygen species (ROS), which is popularly known to cause neuronal death.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Transducción de Señal , Productos Finales de Glicación Avanzada/metabolismoRESUMEN
Chemotherapeutics continue to play a central role in the treatment of a wide variety of cancers. Conventional chemotherapy involving bolus intravenous doses results in severe side effects - in some cases life threatening - delayed toxicity and compromised quality-of-life. Attempts to deliver small drug molecules using liposomes, polymeric nanoparticles, micelles, lipid nanoparticles, etc. have produced limited nanoformulations for clinical use, presumably due to a lack of biocompatibility of the material, costs, toxicity, scalability, and/or lack of effective administration. Naturally occurring small extracellular vesicles, or exosomes, may offer a solution and a viable system for delivering cancer therapeutics. Combined with their inherent trafficking ability and versatility of cargo capacity, exosomes can be engineered to specifically target cancerous cells, thereby minimizing off-target effects, and increasing the efficacy of cancer therapeutics. Exosomal formulations have mitigated the toxic effects of several drugs in murine cancer models. In this article, we review studies related to exosomal delivery of both small molecules and biologics, including siRNA to inhibit specific gene expression, in the pursuit of effective cancer therapeutics. We focus primarily on bovine milk and colostrum exosomes as the cancer therapeutic delivery vehicles based on their high abundance, cost effectiveness, scalability, high drug loading, functionalization of exosomes for targeted delivery, and lack of toxicity. While bovine milk exosomes may provide a new platform for drug delivery, extensive comparison to other nanoformulations and evaluation of long-term toxicity will be required to fully realize its potential.
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Exosomas , Neoplasias , Femenino , Embarazo , Humanos , Animales , Ratones , Leche , Calostro/metabolismo , Exosomas/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Sistemas de Liberación de MedicamentosRESUMEN
Purpose: To determine the level of awareness and knowledge about glaucoma surgery and post-surgery counseling amongst paramedical staff at a tertiary eye-care hospital. Methods: This observational cross-sectional study included a random sample of 94 hospital personnel: 37 general nurse midwives, 47 ophthalmic assistants, and 10 patient caretakers (PCTs). Participants were administered a questionnaire about glaucoma surgery and post-surgery counseling of patients. Results: The study included 41 (43.6%) females and 53 (56.4%) males. The mean age of the participants was 24.85 ± 4.54 years. All participants were aware of trabeculectomy surgery in glaucoma (100%). A total of 95.7% knew that surgery helps in controlling IOP, of whom 57 (60.6%) participants got information during their course of learning. Overall 53 (56.4%) believed that surgery is done when medication failure occurs, and 58 (61.7%) knew that surgery helps in preserving vision. A total of 63 (67.0%) participants knew to counsel patients to visit an ophthalmologist when called for and take the treatment as advised, whereas 74 (78.7%) correctly said to visit an ophthalmologist immediately if pain/diminution of vision/discharge occurs. Overall, PCTs were found to be having significantly better knowledge (P = 0.01) compared to others and they also reported ophthalmologists as the chief source of information. Conclusion: This study revealed that paramedical staff had an excellent awareness of trabeculectomy surgery. However, the knowledge and counseling parts of the questionnaire revealed less than satisfactory responses. So, there is a need to continuously educate paramedical staff members so that they can help in propagating information about the role of glaucoma surgery and the importance of proper follow-up.
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Glaucoma , Trabeculectomía , Masculino , Femenino , Humanos , Adulto Joven , Adulto , Glaucoma/cirugía , Ojo , Encuestas y Cuestionarios , India/epidemiología , ConsejoRESUMEN
Complexes of curcumin with metals have shown much-improved stability, solubility, antioxidant capability, and efficacy when compared to curcumin. The present research investigates the relative bioavailability, antioxidant, and ability to inhibit inflammatory cytokine production of a curcuminoid metal chelation complex of tetrahydrocurcumin-zinc-curcuminoid termed TurmiZn. In vitro uptake assay using pig intestinal epithelial cells showed that TurmiZn has an ~3-fold increase (p ≤ 0.01) in uptake compared to curcumin and a ~2-fold increase (p ≤ 0.01) over tetrahydrocurcumin (THC). In a chicken model, an oral 1-g dose of TurmiZn showed a ~2.5-fold increase of a specific metabolite peak compared to curcumin (p = 0.004) and a ~3-fold increase compared to THC (p = 0.001). Oral doses (5 g/Kg) of TurmiZn in rats also showed the presence of curcumin and THC metabolites in plasma, indicating bioavailability across cell membranes in animals. Determination of the antioxidant activity by a 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging assay indicated that TurmiZn was about 13x better (p ≤ 0.0001) than curcumin and about 4X better (p ≤ 0.0001) than THC, in reducing free radicals. In vitro experiments further showed significant (p ≤ 0.01) reductions of lipopolysaccharide (LPS)-induced proinflammatory cytokines such as interleukin (IL) IL-6, IL-8, IL-15, IL-18, and tumor necrosis factor (TNF)-alpha, while showing a significant (p ≤ 0.01) increase of granulocyte-macrophage colony-stimulating factor (GM-CSF) in dog kidney cells. In vivo cytokine modulations were also observed when TurmiZn was fed for 6 weeks to newborn chickens. TurmiZn reduced IL-1 and IL-6, but significantly reduced (p ≤ 0.01) IL-10 levels while there was a concurrent significant (p = 0.02) increase in interferon gamma compared to controls. Overall, these results indicate that TurmiZn has better bioavailability and antioxidant capability than curcumin or THC and has the ability to significantly modulate cytokine levels. Thus, TurmiZn could be an excellent candidate for a novel ingredient that can be incorporated into food and supplements to help overall health during the aging process.
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Curcumina , Citocinas , Animales , Ratas , Porcinos , Perros , Antioxidantes/farmacología , Curcumina/farmacología , Interleucina-6 , Diarilheptanoides , Disponibilidad Biológica , Zinc , Pollos , Factor de Necrosis Tumoral alfaRESUMEN
Pesticide exposure to eyes is a major source of ocular morbidities in adults and children all over the world. Carbofuran (CF), N-methyl carbamate, pesticide is most widely used as an insecticide, nematicide, and acaricide in agriculture, forestry, and gardening. Contact or ingestion of carbofuran causes high morbidity and mortality in humans and pets. Pesticides are absorbed in the eye faster than other organs of the body and damage ocular tissues very quickly. Carbofuran exposure to eye causes blurred vision, pain, loss of coordination, anti-cholinesterase activities, weakness, sweating, nausea and vomiting, abdominal pain, endocrine, reproductive, and cytotoxic effects in humans depending on amount and duration of exposure. Pesticide exposure to eye injures cornea, conjunctiva, lens, retina, and optic nerve and leads to abnormal ocular movement and vision impairment. Additionally, anticholinesterase pesticides like carbofuran are known to cause salivation, lacrimation, urination, and defecation (SLUD). Carbofuran and its two major metabolites (3-hydroxycarbofuran and 3-ketocarbofuran) are reversible inhibitors of acetylcholinesterase (AChE) which regulates acetylcholine (ACh), a neurohumoral chemical that plays an important role in corneal wound healing. The corneal epithelium contains high levels of ACh whose accumulation by AChE inhibition after CF exposure overstimulates muscarinic ACh receptors (mAChRs) and nicotinic ACh receptors (nAChRs). Hyper stimulation of mAChRs in the eye causes miosis (excessive constriction of the pupil), dacryorrhea (excessive flow of tears), or chromodacryorrhea (red tears). Recent studies reported alteration of autophagy mechanism in human cornea in vitro and ex vivo post carbofuran exposure. This review describes carbofuran toxicity to the eye with special emphasis on corneal morbidities and blindness.
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Carbofurano , Insecticidas , Plaguicidas , Adulto , Niño , Humanos , Carbofurano/toxicidad , Carbofurano/metabolismo , Acetilcolinesterasa/metabolismo , Insecticidas/toxicidad , Insecticidas/metabolismo , Inhibidores de la Colinesterasa , Plaguicidas/toxicidad , Receptores ColinérgicosRESUMEN
Alzheimer's disease (AD) has been the most extensively studied neurological disorders that affects millions of individuals globally and is associated with misfolding of proteins in the brain. Amyloid-ß and tau are predominantly involved in the pathogenesis of AD. Therapeutic interventions and nanotechnological advancements are useful only in managing the AD symptoms and the cure for this disease remains elusive. Exosomes, originating from most cell and tissue types are regarded as a double-edged sword, considering their roles in the progression and treatment of AD. Exosomes can be manipulated as drug delivery vehicles for a wide range of therapeutic cargos-both small molecules and macromolecules. Herein, we review the roles of exosomes in the pathology, diagnosis, and treatment of AD and highlight their application as a drug carrier to the brain for AD treatment.
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Enfermedad de Alzheimer , Exosomas , Humanos , Enfermedad de Alzheimer/metabolismo , Exosomas/metabolismo , Exosomas/patología , Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Proteínas tau/metabolismoRESUMEN
BACKGROUND: The recent second wave and the latest third wave of coronavirus disease 2019 (COVID-19) in India caused havoc on health infrastructure. However, there is a scarcity of studies from India and abroad that compare the second and third waves of the COVID-19 pandemic. We aimed to assess the factors like age, sex, and death comparison among diagnostically proven COVID-19 patients of the Meerut district in both waves. METHODOLOGY: A total of 297554 samples during the second wave (1st March 2021 to 30th June 2021) and 240655 during the third wave (1st January 2022 to 30th April 2022) were tested for reverse transcription polymerase chain reaction (RT-PCR) in the Department of Microbiology, Lala Lajpat Rai Medical College, using The Indian Council of Medical Research (ICMR) approved RT-PCR testing kits. The data like age, sex, place, follow-ups, etc. were recorded and data were analyzed statistically. RESULTS: The RT-PCR positivity of 8.24% for COVID-19 in the second wave while 5.66% of patients in the third wave have been reported. The proportion of positive cases in children ≤10 years in the second and third wave were quite similar i.e., 3.59% and 3.40% respectively, whereas the proportion of positive cases in adolescents (10-20 years) was significantly higher (12.96%) in the third wave in contrast to the second wave (10.15%), while age group (41-60 years) is significantly less (26.65%) in proportion during the third wave in comparison to the second wave (29.50%). The proportion of positivity in young males has significantly increased in the third wave as compared to the second wave. The mortality also decreased significantly by 1/3rd of the second wave. CONCLUSION: The third wave showed low overall positivity (5.66%) as compared to the second wave (8.24%), while the brunt on young children was comparable to the second wave which was assumed to be higher. The mortality and hospitalization also decreased significantly in the second wave. Regular surveillance and analysis should continue to combat this pandemic.
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[This corrects the article DOI: 10.1016/j.omtn.2022.08.011.].
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Taurine, a cysteine-derived zwitterionic sulfonic acid, is a common ingredient in energy drinks and is naturally found in fish and other seafood. In humans, taurine is produced mainly in the liver, and it can also be obtained from food. In target tissues, such as the retina, heart, and skeletal muscle, it functions as an essential antioxidant, osmolyte, and antiapoptotic agent. Taurine is also involved in energy metabolism and calcium homeostasis. Taurine plays a considerable role in bone growth and development, and high-profile reports have demonstrated the importance of its metabolism for bone health. However, these reports have not been collated for more than 10 years. Therefore, this review focuses on taurine-bone interactions and covers recently discovered aspects of taurine's effects on osteoblastogenesis, osteoclastogenesis, bone structure, and bone pathologies (e.g., osteoporosis and fracture healing), with due attention to the taurine-cartilage relationship.
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Osteoporosis , Taurina , Animales , Cartílago/metabolismo , Humanos , Músculo Esquelético/metabolismo , Osteogénesis , Taurina/metabolismoRESUMEN
Purpose: To evaluate the gonioscopic changes in patients receiving Descemet's stripping endothelial keratoplasty (DSEK) without pre-existing ocular hypertension (OHT) and to report its correlation with post-surgery OHT, graft survival, and visual outcomes. Methods: Adult patients who underwent DSEK surgery from April 2014 to March 2018 with at least 2 years of follow-up were analyzed in this retrospective study. Demographic details, indication of DSEK, necessary anterior and posterior segment findings, and the post-DSEK OHT details were documented. Results: A total of 58 patients (23 males and 35 females) with a mean age of 61.44 ± 8.8 years were included in the study. The most common etiology for DSEK surgery was pseudophakic bullous keratopathy in 47 eyes (81.03%). A total of 22.41% (13/58) eyes showed elevated intra-ocular pressure (IOP) following DSEK surgery. The most common cause of IOP elevation was steroid-induced OHT in seven eyes (12.06%). Gonioscopy examination revealed areas of peripheral anterior synechiae (PAS) in 17 (29.3%) eyes. OHT was found in 4/17 (23.5%) eyes having PAS. Three of these cases required trabeculectomy + goniosynechiolysis (GSL), and the fourth case required GSL alone to control IOP. These four cases also required repeat DSEK for failed grafts. The mean pre-operative best corrected visual acuity was 1.62 logMAR (range 1.17-1.77), which gradually improved to 0.79 logMAR (range 0.3-1.77) after 2 years (p < 0.00001). Conclusion: PAS was found to be an important factor associated with post-DSEK ocular hypertension in our study. OHT in PAS cases required definitive surgical treatments to control IOP. It adversely affected the graft survival and in turn affected visual outcomes also.
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Enfermedades de la Córnea , Queratoplastia Endotelial de la Lámina Limitante Posterior , Glaucoma , Hipertensión Ocular , Adulto , Anciano , Femenino , Estudios de Seguimiento , Gonioscopía , Supervivencia de Injerto , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Agudeza VisualRESUMEN
Emerging viral diseases, such as Ebola, SARS, MERS, and the pathogen causing COVID-19, SARS-CoV-2, present a challenge for the development of therapeutics because of strict biosafety handling procedures and rapid mutation of their genomes. To facilitate the development of an adaptable and testable therapeutic model system, a colostrum exosome-based nanoparticle delivery system, EPM (exosome-PEI matrix), that overcomes stringent biosafety containment, was used to mimic the expression of viral proteins. This system would greatly expand the number of laboratories actively participating in the screening of potential therapeutics. EPM technology can deliver both plasmid DNA and siRNA to both simulate viral gene expression and screen potential antiviral siRNA therapeutics. Using this nanoplatform, three key SARS-CoV-2 proteins (the spike glycoprotein, nucleocapsid, and replicase) were expressed in vitro and in vivo. In vitro, several viral gene-targeting siRNAs were screened to determine knockdown efficiency, with some siRNA duplexes resulting in 80%-95% knockdown of corresponding protein expression. Moreover, in vivo experiments introducing the spike protein and nucleocapsid by EPM resulted in the production of antibodies against the viral antigen, measured up to 45 d after target delivery. Together, these findings support the efficacy of the EPM delivery system to establish a model for screening antiviral therapeutics-reduced biosafety level.
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Psoriasis is a chronic skin auto-inflammatory and systemic disorder. Novel treatments are needed to solve a plethora of cases refractory to current treatment regimens. N-bromotaurine (TauNH-Br), a natural taurine oxidizing derivative produced by inflammatory cells, has anti-inflammatory, antiproliferative, and antimicrobial properties. This evidence prompted us to use TauNH-Br as a local agent for treatment of therapy-refractory psoriasis. Two pustular-plaque psoriasis cases, unresponsive to systemic and local treatments, one with localized lesions and one with generalized lesions, were selected. Both applications primarily indicated a sufficient curative activity of 1% TauNH-Br in psoriasis lesions. Moreover, TauNH-Br co-administration with taurine and a novel olive oil formulation cut in half the time needed for TauNH-Br alone to cause the same regression of equivalent psoriasis plaque lesions in the same patient. Importantly, all adverse effects of TauNH-Br (erythema, itching, bleeding) could be minimized by the combination therapy. Periods of 2-7 weeks to achieve almost complete regression with this formulation were remarkably short as compared to conventional treatment regimens that both patients had followed previously. Of note, there was no relapse within 3 months of monitoring. Combination formulations containing TauNH-Br and olive oil could become an advantageous topical medication for treatment of psoriasis.
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Exantema , Psoriasis , Administración Tópica , Humanos , Aceite de Oliva/uso terapéutico , Psoriasis/tratamiento farmacológico , Taurina/análogos & derivados , Taurina/farmacología , Taurina/uso terapéuticoRESUMEN
Breast cancer (BC) is the most common type of malignancy which covers almost one-fourth of all the cancers diagnosed in women. Conventionally, chemo-, hormonal-, immune-, surgery, and radiotherapy are the clinically available therapies for BC. However, toxicity and other related adverse effects are still the major challenges. A variety of nano platforms have been reported to overcome these limitations, among them, exosomes provide a versatile platform not only for the diagnosis but also as a delivery vehicle for drugs. Exosomes are biological nanovesicles made up of a lipidic bilayer and known for cell-to-cell communication. Exosomes have been reported to be present in almost all bodily fluids, viz., blood, milk, urine, saliva, pancreatic juice, bile, peritoneal, and cerebrospinal fluid. Such characteristics of exosomes have attracted immense interest in cancer diagnosis and therapy. They can deliver bioactive moieties such as protein, lipids, hydrophilic as well as hydrophobic drugs, various RNAs to both distant and nearby recipient cells as well as have specific biological markers. By considering the growing interest of the scientific community in this field, we comprehensively compiled the information about the biogenesis of exosomes, various isolation methods, the drug loading techniques, and their diverse applications in breast cancer diagnosis and therapy along with ongoing clinical trials which will assist future scientific endeavors in a more organized direction.
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Exosomes or small extracellular vesicles (EVs) are natural nanoparticles and known to play essential roles in intercellular communications, carrying a cargo of a broad variety of lipids, proteins, metabolites, RNAs (mRNA, miRNA, tRNA, long non-coding RNA), and DNAs (mtDNA, ssDNA, dsDNA) [...].
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Cancer is one of the leading global causes of death in both men and women. Colorectal cancer (CRC) alone accounts for â¼10 % of total new global cases and poses an over 4% lifetime risk of developing cancer. Recent advancements in the field of biotechnology and microbiology concocted novel microbe-based therapies to treat various cancers, including CRC. Microbes have been explored for human use since centuries, especially for the treatment of various ailments. The utility of microbes in cancer therapeutics is widely explored, and various bacteria, fungi, and viruses are currently in use for the development of cancer therapeutics. The human gut hosts about 100 trillion microbes that release their metabolites in active, inactive, or dead conditions. Microbial secondary metabolites, proteins, immunotoxins, and enzymes are used to target cancer cells to induce cell cycle arrest, apoptosis, and death. Various approaches, such as dietary interventions, the use of prebiotics and probiotics, and fecal microbiota transplantation have been used to modulate the gut microbiota in order to prevent or treat CRC pathogenesis. The present review highlights the role of the gut microbiota in CRC precipitation, the potential mechanisms and use of microorganisms as CRC biomarkers, and strategies to modulate microbiota for the prevention and treatment of CRC.