Prenatal Arsenic Exposure on DNA Methylation of C18ORF8 and ADAMTS9 Genes of Newborns from the POSGRAD Birth Cohort Study.

Exposure to arsenic (As) is a public health problem associated with cancer (skin and colon) and it has been reported that epigenetic changes may be a potential mechanism of As carcinogenesis. It is pertinent to evaluate this process in genes that have been associated with cancer, such as ADAMTS9 and C18ORF8. Gestation and delivery data were obtained from the POSGRAD study. Exposure to As was measured in urine during pregnancy. Gene methylation was performed by sodium bisulfite sequencing; 26 CpG sites for the C18ORF8 gene and 21 for ADAMTS9 were analyzed. These sites are located on the CpG islands near the start of transcription. Sociodemographic characteristics were obtained by a questionnaire. The statistical analysis was performed using multiple linear regression models adjusted for potential confounders. Newborns with an As exposure above 49.4 µg g-1 showed a decrease of 0.21% on the methylation rate in the sites CpG15, CpG19, and CpG21 of the C18ORF8 gene (adjusted ß = -0.21, p-value = 0.02). No statistically significant association was found between prenatal exposure to As and methylation of the ADAMTS9 gene. Prenatal exposure to As was associated with decreased DNA methylation at the CpG15, CpG19, and CpG21 sites of the C18ORF8 gene. These sites can provide information to elucidate epigenetic mechanisms associated with prenatal exposure to As and cancer.

STAT5 Is Necessary for the Metabolic Switch Induced by IL-2 in Cervical Cancer Cell Line SiHa.

The tumor cells reprogram their metabolism to cover their high bioenergetic demands for maintaining uncontrolled growth. This response can be mediated by cytokines such as IL-2, which binds to its receptor and activates the JAK/STAT pathway. Some reports show a correlation between the JAK/STAT pathway and cellular metabolism, since the constitutive activation of STAT proteins promotes glycolysis through the transcriptional activation of genes related to energetic metabolism. However, the role of STAT proteins in the metabolic switch induced by cytokines in cervical cancer remains poorly understood. In this study, we analyzed the effect of IL-2 on the metabolic switch and the role of STAT5 in this response. Our results show that IL-2 induces cervical cancer cell proliferation and the tyrosine phosphorylation of STAT5. Also, it induces an increase in lactate secretion and the ratio of NAD+/NADH, which suggest a metabolic reprogramming of their metabolism. When STAT5 was silenced, the lactate secretion and the NAD+/NADH ratio decreased. Also, the expression of HIF1α and GLUT1 decreased. These results indicate that STAT5 regulates IL-2-induced cell proliferation and the metabolic shift to aerobic glycolysis by regulating genes related to energy metabolism. Our results suggest that STAT proteins modulate the metabolic switch in cervical cancer cells to attend to their high demand of energy required for cell growth and proliferation.

Modifying the Basicity of the dNTP Leaving Group Modulates Precatalytic Conformational Changes of DNA Polymerase ß.

The catalytic function of DNA polymerase ß (pol ß) fulfills the gap-filling requirement of the base excision DNA repair pathway by incorporating a single nucleotide into a gapped DNA substrate resulting from the removal of damaged DNA bases. Most importantly, pol ß can select the correct nucleotide from a pool of similarly structured nucleotides to incorporate into DNA in order to prevent the accumulation of mutations in the genome. Pol ß is likely to employ various mechanisms for substrate selection. Here, we use dCTP analogues that have been modified at the ß,γ-bridging group of the triphosphate moiety to monitor the effect of leaving group basicity of the incoming nucleotide on precatalytic conformational changes, which are important for catalysis and selectivity. It has been previously shown that there is a linear free energy relationship between leaving group pKa and the chemical transition state. Our results indicate that there is a similar relationship with the rate of a precatalytic conformational change, specifically, the closing of the fingers subdomain of pol ß. In addition, by utilizing analogue ß,γ-CHX stereoisomers, we identified that the orientation of the ß,γ-bridging group relative to R183 is important for the rate of fingers closing, which directly influences chemistry.

Temporal coordination of the transcription factor response to H2O2 stress.

Oxidative stress from excess H2O2 activates transcription factors that restore redox balance and repair oxidative damage. Although many transcription factors are activated by H2O2, it is unclear whether they are activated at the same H2O2 concentration, or time. Dose-dependent activation is likely as oxidative stress is not a singular state and exhibits dose-dependent outcomes including cell-cycle arrest and cell death. Here, we show that transcription factor activation is both dose-dependent and coordinated over time. Low levels of H2O2 activate p53, NRF2 and JUN. Yet under high H2O2, these transcription factors are repressed, and FOXO1, NF-κB, and NFAT1 are activated. Time-lapse imaging revealed that the order in which these two groups of transcription factors are activated depends on whether H2O2 is administered acutely by bolus addition, or continuously through the glucose oxidase enzyme. Finally, we provide evidence that 2-Cys peroxiredoxins control which group of transcription factors are activated.

Drugs and natural products for the treatment of COVID-19 during 2020, the first year of the pandemic.

This work aimed to show which treatments showed efficacy against coronavirus disease 2019 (COVID-19); therefore, the results of 37 clinical trials started in 2020 and completed in 2021 are reviewed and discussed here. These were selected from databases, excluding vaccines, computational studies, in silico, in vitro, and those with hyperimmune sera from recovered patients. We found 34 drugs, one vitamin, and one herbal remedy with pharmacological activity against symptomatic COVID-19. They reduced mortality, disease progression, or recovery time. For each treatment, the identifier and type of trial, the severity of the disease, the sponsor, the country where the trial was conducted, and the trial results are presented. The drugs were classified according to their mechanism of action. Several drugs that reduced mortality also reduced inflammation in the most severe cases. These include some that are not considered anti-inflammatory, such as Aviptadil, pyridostigmine bromide, anakinra, imatinib, baricitinib, and bevacizumab, as well as the combination of ivermectin, aspirin, dexamethasone, and enoxaparin. Nigella sativa seeds with honey have also been reported to have therapeutic activity. On the other hand, tofacitinib, novaferon with ritonavir, and lopinavir were also effective, as well as in combination with antiviral therapies such as danoprevir with ritonavir. The natural products colchicine and Vitamin D3 were only effective in patients with mild-to-moderate COVID-19, as was hydroxychloroquine. Drug repositioning has been the main tool in the search for effective therapies by expanding the pharmacological options available to patients.

El objetivo del presente trabajo fue conocer qué tratamientos mostraron efectividad contra COVID-19, para lo cual se revisan y discuten los resultados de 37 estudios clínicos iniciados durante 2020 y concluidos en 2021. Estos fueron seleccionados de bases de datos, excluyendo vacunas, estudios computacionales, in silico, in vitro y con sueros hiperinmunes de pacientes recuperados. Se documentaron 34 fármacos, una vitamina y un remedio herbolario, con actividad farmacológica ante COVID-19 sintomático. Estos redujeron la mortalidad, el progreso de la enfermedad, o el tiempo de recuperación. Para cada tratamiento se presenta identificador y tipo de estudio, la gravedad de la enfermedad, patrocinador, país donde se realizó, así como sus resultados. Los fármacos se clasificaron de acuerdo con su mecanismo de acción. Varios fármacos que redujeron la mortalidad también disminuyeron la inflamación en los casos más graves. Esto incluyendo algunos no considerados antiinflamatorios, como el aviptadil, el bromuro de piridostigmina, el anakinra, el imatinib, el baricitinib y el bevacizumab, así como la combinación de ivermectina, aspirina, dexametasona y enoxaparina. También se reportaron con actividad terapéutica las semillas de Nigella sativa con miel. Además, resultaron efectivos el tofacitinib, el novaferón con ritonavir y lopinavir, así como los antivirales en terapias combinadas como el danoprevir con ritonavir. Los productos naturales colchicina y vitamina D3, solo tuvieron actividad en los pacientes en estado leve a moderado de la COVID-19, así como la hidroxicloroquina. El reposicionamiento de fármacos fue la principal herramienta para buscar terapias efectivas ampliando las opciones farmacológicas accesibles a los pacientes.

Pulmonary Artery Aneurysm Associated with Sarcoidosis in a 75-year-old with Heart Failure: The Challenges of Diagnosis and Management.

Introduction: Pulmonary artery aneurysm (PAA) is a rare abnormality of pulmonary vasculature. It can be idiopathic or secondary to various pathologies, frequently with multiple factors leading to its formation. We report the case of a man with concomitant sarcoidosis and PAA. Case description: A 75-year-old male with a diagnosis of pulmonary sarcoidosis was referred to the Cardiology department due to heart failure with reduced left ventricular ejection fraction (LVEF). The transthoracic echocardiogram revealed mildly reduced LVEF, aortic root and pulmonary artery (PA) dilatation, and no signs of pulmonary hypertension (PH). Cardiac magnetic resonance imaging was performed, revealing mild left ventricular dilation, LVEF of 40%, main PA dilation (43 mm) and a pattern of late gadolinium enhancement suggestive of cardiac sarcoidosis. At follow-up, a thoracic computed tomography (CT) angiography scan revealed ascending aorta ectasia and giant main PA aneurysm (60 mm). A right heart catheterisation was performed, and a mean PA pressure of 34 mmHg was obtained. Given the clinical context, the patient was considered to have PH due to lung disease and left heart disease, and PAA was possible due to vascular granulomatous involvement by sarcoidosis. Conclusion: PAA is a rare finding and mostly occurs in the setting of PH. Sarcoidosis is a granulomatous disease that mostly affects the lungs, but the sarcoid involvement of great vessels has been described. In this clinical case, the probable cause for the PA fragility leading to aneurysm formation remains sarcoid vascular infiltration, regarding the discrepancy between the PA dimensions and mildly elevated PA pressure. LEARNING POINTS: Pulmonary artery aneurysm is a rare abnormality of pulmonary vasculature that can be idiopathic or a consequence of pulmonary hypertension, congenital heart disease, infection, vasculitis or collagenopathies.Due to the low incidence of this disease, there are no guidelines for its diagnosis, management or follow-up, and treatment is based on the underlying aetiology, aneurysm dimensions and occurrence of symptoms.Sarcoidosis is a multisystem disorder of unknown aetiology characterised by non-caseating granulomas that mostly involve the lungs, but can also affect skin, eyes, and lymph nodes. Sarcoid involvement of great vessels has been rarely described.

Left Ventricular Pseudoaneurysm: A Bursting Threat.

A 55-year-old man submitted to emergency surgery due to cardiac perforation by stabbing. One month later, he presented with chest pain, and a transthoracic echocardiogram revealed moderate-severe mitral regurgitation. After 6 months, a new transthoracic echocardiogram showed a left ventricular pseudoaneurysm, being later submitted to pseudoaneurysm exclusion and mitral valvuloplasty.

Design and Characterization of Ocular Inserts Loaded with Dexamethasone for the Treatment of Inflammatory Ophthalmic Disease.

The short precorneal residence time of ophthalmic drops is associated with their low absorption; therefore, the development of ocular inserts capable of prolonging and controlling the ophthalmic release of drugs is an interesting option in the design and development of these drugs. A surface response design was developed, specifically the Central Composite Design (CCD), to produce ophthalmic films loaded with Dexamethasone (DEX) by the solvent evaporation method having experimental levels of different concentrations of previously selected polymers (PVP K-30 and Eudragit RS100.). Once optimization of the formulation was obtained, the in vivo test was continued. The optimal formulation obtained a thickness of 0.265 ± 0.095 mm, pH of 7.11 ± 0.04, tensile strength of 15.50 ± 3.94 gF, humidity (%) of 22.54 ± 1.7, mucoadhesion strength of 16.89 ± 3.46 gF, chemical content (%) of 98.19 ± 1.124, release of (%) 13,510.71, and swelling of 0.0403 ± 0.023 g; furthermore, in the in vivo testing the number and residence time of PMN cells were lower compared to the Ophthalmic Drops. The present study confirms the potential use of polymeric systems using PVPK30 and ERS100 as a new strategy of controlled release of ophthalmic drugs by controlling and prolonging the release of DEX at the affected site by decreasing the systemic effects of the drug.

Rheumatoid Arthritis and Pericardial Effusion - A Unique Major Manifestation.

Introduction: Pericardial effusion is common in the setting of rheumatoid arthritis (RA); however, it is rarely its first manifestation. Case description: An 82-year-old male presented with abdominal pain, vomiting and fever. Blood analysis revealed elevated systemic inflammatory markers, and an abdominal computed tomography scan revealed non-specific alveolar condensation of the right pulmonary base and pericardial effusion subsequently quantified as medium size by transthoracic echocardiography. A large aetiological panel was requested, with the autoimmunity study revealing high levels of rheumatoid factor (RF) and anti-citrullinated cyclic peptide (anti-CCP) antibodies. Since the patient did not present articular involvement, the initial hypothesis was pericardial effusion due to pneumonia and no specific treatment for RA was started. At follow-up, the pericardial effusion recurred and a pericardiocentesis was performed. The pericardial fluid analysis was sterile, and no malignant cells were identified. A new serological study confirmed high levels of RF and anti-CCP antibodies, and immunomodulatory treatment was initiated. After one year, the pericardial effusion recurred due to non-compliance with immunomodulatory therapy. A surgical pleuro-pericardial window was performed, and the cytological study of the pericardial patch revealed submesothelial thickening and foci of perivascular lymphocytic infiltrate. The patient remained asymptomatic. Discussion: After exclusion of a large spectrum of infectious and non-infectious causes and the relapse after suspension of immunomodulatory treatment, the most probable aetiology for the pericardial effusion remains RA. Conclusion: Pericardial syndromes can be the first manifestation of AR even in the absence of articular symptoms and this disease must be considered in the aetiological investigation. LEARNING POINTS: The occurrence of pericardial effusion in the setting of rheumatoid arthritis (RA) is a usual finding but this form of extra-articular manifestation is possibly the first and only presentation of the disease.In the case of recurrent pericardial effusion, the diagnosis of RA must be considered in the aetiological investigation even in the absence of more common manifestations of the disease.

Drugs and natural products for the treatment of COVID-19 during 2020, the first year of the pandemic / Fármacos y productos naturales para el tratamiento de la COVID-19 durante 2020, el primer año de la pandemia

Abstract This work aimed to show which treatments showed efficacy against coronavirus disease 2019 (COVID-19); therefore, the results of 37 clinical trials started in 2020 and completed in 2021 are reviewed and discussed here. These were selected from databases, excluding vaccines, computational studies, in silico, in vitro, and those with hyperimmune sera from recovered patients. We found 34 drugs, one vitamin, and one herbal remedy with pharmacological activity against symptomatic COVID-19. They reduced mortality, disease progression, or recovery time. For each treatment, the identifier and type of trial, the severity of the disease, the sponsor, the country where the trial was conducted, and the trial results are presented. The drugs were classified according to their mechanism of action. Several drugs that reduced mortality also reduced inflammation in the most severe cases. These include some that are not considered anti-inflammatory, such as Aviptadil, pyridostigmine bromide, anakinra, imatinib, baricitinib, and bevacizumab, as well as the combination of ivermectin, aspirin, dexamethasone, and enoxaparin. Nigella sativa seeds with honey have also been reported to have therapeutic activity. On the other hand, tofacitinib, novaferon with ritonavir, and lopinavir were also effective, as well as in combination with antiviral therapies such as danoprevir with ritonavir. The natural products colchicine and Vitamin D3 were only effective in patients with mild-to-moderate COVID-19, as was hydroxychloroquine. Drug repositioning has been the main tool in the search for effective therapies by expanding the pharmacological options available to patients.

Resumen El objetivo del presente trabajo fue conocer qué tratamientos mostraron efectividad contra COVID-19, para lo cual se revisan y discuten los resultados de 37 estudios clínicos iniciados durante 2020 y concluidos en 2021. Estos fueron seleccionados de bases de datos, excluyendo vacunas, estudios computacionales, in silico, in vitro y con sueros hiperinmunes de pacientes recuperados. Se documentaron 34 fármacos, una vitamina y un remedio herbolario, con actividad farmacológica ante COVID-19 sintomático. Estos redujeron la mortalidad, el progreso de la enfermedad, o el tiempo de recuperación. Para cada tratamiento se presenta identificador y tipo de estudio, la gravedad de la enfermedad, patrocinador, país donde se realizó, así como sus resultados. Los fármacos se clasificaron de acuerdo con su mecanismo de acción. Varios fármacos que redujeron la mortalidad también disminuyeron la inflamación en los casos más graves. Esto incluyendo algunos no considerados antiinflamatorios, como el aviptadil, el bromuro de piridostigmina, el anakinra, el imatinib, el baricitinib y el bevacizumab, así como la combinación de ivermectina, aspirina, dexametasona y enoxaparina. También se reportaron con actividad terapéutica las semillas de Nigella sativa con miel. Además, resultaron efectivos el tofacitinib, el novaferón con ritonavir y lopinavir, así como los antivirales en terapias combinadas como el danoprevir con ritonavir. Los productos naturales colchicina y vitamina D3, solo tuvieron actividad en los pacientes en estado leve a moderado de la COVID-19, así como la hidroxicloroquina. El reposicionamiento de fármacos fue la principal herramienta para buscar terapias efectivas ampliando las opciones farmacológicas accesibles a los pacientes.

Synergistic Effect of Retinoic Acid and Lactoferrin in the Maintenance of Gut Homeostasis.

Lactoferrin (LF) is a glycoprotein that binds to iron ions (Fe2+) and other metallic ions, such as Mg2+, Zn2+, and Cu2+, and has antibacterial and immunomodulatory properties. The antibacterial properties of LF are due to its ability to sequester iron. The immunomodulatory capability of LF promotes homeostasis in the enteric environment, acting directly on the beneficial microbiota. LF can modulate antigen-presenting cell (APC) biology, including migration and cell activation. Nonetheless, some gut microbiota strains produce toxic metabolites, and APCs are responsible for initiating the process that inhibits the inflammatory response against them. Thus, eliminating harmful strains lowers the risk of inducing chronic inflammation, and consequently, metabolic disease, which can progress to type 2 diabetes mellitus (T2DM). LF and retinoic acid (RA) exhibit immunomodulatory properties such as decreasing cytokine production, thus modifying the inflammatory response. Their activities have been observed both in vitro and in vivo. The combined, simultaneous effect of these molecules has not been studied; however, the synergistic effect of LF and RA may be employed for enhancing the secretion of humoral factors, such as IgA. We speculate that the combination of LF and RA could be a potential prophylactic alternative for the treatment of metabolic dysregulations such as T2DM. The present review focuses on the importance of a healthy diet for a balanced gut and describes how probiotics and prebiotics with immunomodulatory activity as well as inductors of differentiation and cell proliferation could be acquired directly from the diet or indirectly through the oral administration of formulations aimed to maintain gut health or restore a eubiotic state in an intestinal environment that has been dysregulated by external factors such as stress and a high-fat diet.

Chemical Analysis and Antidiabetic Potential of a Decoction from Stevia serrata Roots.

A decoction of the roots (31.6-316 mg/kg) from Stevia serrata Cav. (Asteraceae) as well as the main component (5-150 mg/kg) showed hypoglycemic and antihyperglycemic effects in mice. The fractionation of the active extract led to the isolation of dammaradiene acetate (1), stevisalioside A (2), and three new chemical entities characterized by spectroscopic methods and named stevisaliosides B-D (3-5). Glycoside 2 (5 and 50 mg/kg) decreased blood glucose levels and the postprandial peak during oral glucose and insulin tolerance tests in STZ-hyperglycemic mice. Compounds 1-5 were tested also against PTP1B1-400 and showed IC50 values of 1180.9 ± 0.33, 526.8 ± 0.02, 532.1 ± 0.03, 928.2 ± 0.39, and 31.8 ± 1.09 µM, respectively. Compound 5 showed an IC50 value comparable to that of ursolic acid (IC50 = 30.7 ± 0.00 µM). Docking studies revealed that 2-5 and their aglycones bind to PTP1B1-400 in a pocket formed by the C-terminal region. The volatilome of S. serrata was characterized by a high content of (E)-longipinene, spathulenol, guaiadiene, seychellene, and aromandendrene. Finally, a UHPLC-UV method was developed and validated to quantify the content of 2 in the decoction of the plant.

Ceftriaxone-Loaded Polymeric Microneedles, Dressings, and Microfibers for Wound Treatment.

The objective of this study was to create polymeric dressings, microfibers, and microneedles (MN) loaded with ceftriaxone, using PMVA (Poly (Methyl vinyl ether-alt-maleic acid), Kollicoat® 100P, and Kollicoat® Protect as polymers to treat diabetic wounds and accelerate their recovery. These formulations were optimized through a series of experiments and were subsequently subjected to physicochemical tests. The results of the characterization of the dressings, microfibers, and microneedles (PMVA and 100P) were, respectively, a bioadhesion of 281.34, 720, 720, 2487, and 510.5 gf; a post-humectation bioadhesion of 186.34, 831.5, 2380, and 630.5 gf, tear strength of 2200, 1233, 1562, and 385 gf, erythema of 358, 8.4, 227, and 188; transepidermal water loss (TEWL) of 2.6, 4.7, 1.9, and 5.2 g/h·m2; hydration of 76.1, 89.9, 73.5, and 83.5%; pH of 4.85, 5.40, 5.85, and 4.85; and drug release (Peppas kinetics release) of n: 0.53, n: 0.62, n: 0.62, and n: 0.66). In vitro studies were performed on Franz-type diffusion cells and indicated flux of 57.1, 145.4, 718.7, and 2.7 µg/cm2; permeation coefficient (Kp) of 13.2, 19.56, 42, and 0.00015 cm2/h; and time lag (tL) of 6.29, 17.61, 27. 49, and 22.3 h, respectively, in wounded skin. There was no passage of ceftriaxone from dressings and microfibers to healthy skin, but that was not the case for PMVA/100P and Kollicoat® 100P microneedles, which exhibited flux of 194 and 0.4 µg/cm2, Kp of 11.3 and 0.00002 cm2/h, and tL of 5.2 and 9.7 h, respectively. The healing time of the formulations in vivo (tests carried out using diabetic Wistar rats) was under 14 days. In summary, polymeric dressings, microfibers, and microneedles loaded with ceftriaxone were developed. These formulations have the potential to address the challenges associated with chronic wounds, such as diabetic foot, improving the outcomes.

JAK/STAT Signaling and Cervical Cancer: From the Cell Surface to the Nucleus.

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway constitutes a rapid signaling module from the cell surface to the nucleus, and activates different cellular responses, such as proliferation, survival, migration, invasion, and inflammation. When the JAK/STAT pathway is altered, it contributes to cancer progression and metastasis. STAT proteins play a central role in developing cervical cancer, and inhibiting the JAK/STAT signaling may be necessary to induce tumor cell death. Several cancers show continuous activation of different STATs, including cervical cancer. The constitutive activation of STAT proteins is associated with a poor prognosis and overall survival. The human papillomavirus (HPV) oncoproteins E6 and E7 play an essential role in cervical cancer progression, and they activate the JAK/STAT pathway and other signals that induce proliferation, survival, and migration of cancer cells. Moreover, there is a crosstalk between the JAK/STAT signaling cascade with other signaling pathways, where a plethora of different proteins activate to induce gene transcription and cell responses that contribute to tumor growth. Therefore, inhibition of the JAK/STAT pathway shows promise as a new target in cancer treatment. In this review, we discuss the role of the JAK/STAT pathway components and the role of the HPV oncoproteins associated with cellular malignancy through the JAK/STAT proteins and other signaling pathways to induce tumor growth.

Hutchinson-Gilford Progeria Syndrome: Cellular Mechanisms and Therapeutic Perspectives.

In humans, aging is characterized by a gradual decline of physical and psychological functions, with the concomitant onset of chronic-degenerative diseases, which ultimately lead to death. The study of Hutchinson-Gilford progeria syndrome (HGPS), a premature aging disorder that recapitulates several features of natural aging, has provided important insights into deciphering the aging process. The genetic origin of HGPS is a de novo point mutation in the LMNA gene that drives the synthesis of progerin, mutant version of lamin A. Progerin is aberrantly anchored to the nuclear envelope disrupting a plethora of molecular processes; nonetheless, how progerin exerts a cascade of deleterious alterations at the cellular and systemic levels is not fully understood. Over the past decade, the use of different cellular and animal models for HGPS has allowed the identification of the molecular mechanisms underlying HGPS, paving the way towards the development of therapeutic treatments against the disease. In this review, we present an updated overview of the biology of HGPS, including its clinical features, description of key cellular processes affected by progerin (nuclear morphology and function, nucleolar activity, mitochondrial function, protein nucleocytoplasmic trafficking and telomere homeostasis), as well as discussion of the therapeutic strategies under development.

Pituitary apoplexy and cerebral infarction.

Pituitary apoplexy (PA) is a possible complication of pituitary adenoma but is rarely followed by cerebral infarction. The mechanism by which this occurs is not totally understood but is believed to have multiple aetiologies such as arterial compression due to mass effect, vasospasm induced by the presence of blood or by vasoactive agents. In this report, we present a man in his 80s with known pituitary adenoma with a sudden onset of left central facial palsy, left hemiparesis, paresis of the VI left pair and previously unrecognised atrial fibrillation in the ECG. At first, the signs of haemorrhage on imaging were unnoticed, which led to a diagnosis of ischaemic stroke that was submitted to thrombolysis. Due to complications during hospitalisation, the team suspected of PA with panhypopituitarism, confirmed by brain MRI and blood tests. The patient underwent conservative management with glucocorticoids with resolution of the acute adrenal insufficiency related symptoms.

Chitosan Nanoparticles as Oral Drug Carriers.

The use of nanoparticles as drug delivery systems has increased in importance in the last decades. Despite the disadvantages of difficulty swallowing, gastric irritation, low solubility, and poor bioavailability, oral administration stands out as the most widely used route for therapeutic treatments, though it may not always be the most effective route. The effect of the first hepatic pass is one of the primary challenges that drugs must overcome to carry out their therapeutic effect. For these reasons, controlled-release systems based on nanoparticles synthesized from biodegradable natural polymers have been reported to be very efficient in enhancing oral delivery in multiple studies. Chitosan has been shown to have an extensive variability of properties and roles in the pharmaceutical and health fields; of its most important properties are the ability to encapsulate and transport drugs within the body and enhance the drug interaction with the target cells, which improves the efficacy of the encapsulated drugs. The physicochemical properties of chitosan give it the ability to form nanoparticles through multiple mechanisms, which will be addressed in this article. The present review article focuses on highlighting the applications of chitosan nanoparticles for oral drug delivery.

Anti-Inflammatory Effects of Flavonoids in Common Neurological Disorders Associated with Aging.

Aging reduces homeostasis and contributes to increasing the risk of brain diseases and death. Some of the principal characteristics are chronic and low-grade inflammation, a general increase in the secretion of proinflammatory cytokines, and inflammatory markers. Aging-related diseases include focal ischemic stroke and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Flavonoids are the most common class of polyphenols and are abundantly found in plant-based foods and beverages. A small group of individual flavonoid molecules (e.g., quercetin, epigallocatechin-3-gallate, and myricetin) has been used to explore the anti-inflammatory effect in vitro studies and in animal models of focal ischemic stroke and AD and PD, and the results show that these molecules reduce the activated neuroglia and several proinflammatory cytokines, and also, inactivate inflammation and inflammasome-related transcription factors. However, the evidence from human studies has been limited. In this review article, we highlight the evidence that individual natural molecules can modulate neuroinflammation in diverse studies from in vitro to animal models to clinical studies of focal ischemic stroke and AD and PD, and we discuss future areas of research that can help researchers to develop new therapeutic agents.

Fruit Extract of Sechium chinantlense (Lira & F. Chiang) Induces Apoptosis in the Human Cervical Cancer HeLa Cell Line.

Sechium edule (Cucurbitaceae) is a commercial species of chayote and is just one of several species in the genus Sechium, whose extracts inhibit proliferation in tumor cell lines. The capacity of the wild species Sechium chinantlense (SCH) as an antitumor agent is unknown, as is the mechanism of action. In the present study, HeLa cervical cancer and HaCaT normal cell lines were treated with SCH and cell proliferation was inhibited in both cell lines in a dose-dependent manner similar to the effect of the antineoplastic agent cisplatin (Cis). Additionally, SCH arrested cell cycle progression but only in HeLa cells and induced apoptosis, as shown by phosphatidylserine translocation and caspase-3 activation, while Cis did so in both cell lines. Exploration of the mechanism of action of SCH in HeLa cells suggests that apoptosis was mediated by the intrinsic signaling pathway since there was no activation of caspase-8, but there was a release of cytochrome-c. These findings suggest that the SCH extract has the potential to selectively kill tumor cells by promoting apoptosis, without harming nontumor cells.