11 research outputs found
POR UNA CULTURA DE PAZ: UNA MIRADA DESDE LAS CIENCIAS DE LA CONDUCTA
En
virtud
de
lo
anterior,
los
estudiosos
de
las
ciencias
de
la
conducta
de
la
Universidad
Autónoma
del
Estado
de
México,
ante
la
persistencia
y
proliferación
de
estos
hechos
en
diversas
partes
del
Mundo
y
de
nuestro
país
en
particular, se
convocó
a
los
estudiosos
interesados
y
a
la
sociedad
en
general
a
presentar
trabajos
para
analizar,
debatir
y
proponer
estrategias
de
acción
y
dirección,
que
fortalezcan
una
convivencia y bienestar con sentido humanista para una cultura de paz.
El
presente
texto
es
producto
de
esta convocatoria
que
recoge
los
trabajos
de
los
interesados
en
la
temática,
de
diferentes
países
(España,
Argentina,
Cuba,
Brasil,
Costa
Rica
y
México)
retomando
con
ello
sus
experiencias
relativas
al
estudio,
análisis,
comprensión
e
instrumentación
de
la
cultura
de
paz
en
los
distintos
ámbitos
institucionales
en
los
que
participan:
educativo,
salud,
penitenciario,
social,
laboral,
familia,
alimentario,
psicológico,
por
mencionar
algunos.
El
presente
libro,
propicia
un
espacio
de
reflexión,
diálogo
y
posicionamiento
de
las
ciencias
de
la
conducta
para
la
apropiación,
análisis,
debate
y
propuestas
que
fortalezcan
una
cultura
de
paz
a
través
de
la
convivencia
y
el
bienestar
social
con
sentido
humanista.
El
sistema
económico
neoliberal
y
el
proceso
de
globalización
han
contribuido
al
logro
de
avances
significativos
en
la
ciencia
y
la
tecnología,
pero
también
han
propiciado
la
polarización
de
las
sociedades
lo
que
ha
impactado
de
manera
negativa
a
la
sociedad
en
su
conjunto,
pero
en
mayor
medida
a
los grupos
vulnerables. Dicha
polarización
ha
traído
consigo
un
desarrollo
desigual
del
mundo
que
se
expresa
de
diferentes
maneras
tanto
en
países
desarrollados
como
en
los
llamados
del
tercer
mundo,
en
donde
no
están
satisfechas
las
necesidades
humanas
elementales
de
todos
los
sectores
de
la
población,
siempre
falta
algo.
Si
a
esto
le
sumamos
los
conflictos
internacionales por
diferentes
motivos
que
enfrentan
algunas
naciones,
una
insuficiente
cobertura
educativa
y
de
salud,
desempleo
y
pobreza
extrema,
entre
otras
cosas;
estamos
frente
a
retos
de
gran
envergadura
para
los
gobiernos,
para
los
estudiosos
y
para
la
sociedad
civil
en
general. Uno
de
los
intentos
para
frenar
y prevenir
la
agudización
de
estas
problemáticas
es
la
cultura
de
paz,
cuyo
estudio
y propuestas
han
ido
avanzando
en
diferentes
sentidos
y
de
manera
favorable,
el
tema
está
presente
en
diferentes
Organismos
Internacionales
como
la
ONU,
la
UNESCO,
la
OCDE,
El
Banco
Mundial,
entre
otros.
Pero
falta
mucho
por
hacer.Universidad Autónoma del Estado de Méxic
Redox Regulation of Nrf2 in Cisplatin-Induced Kidney Injury
Cisplatin, a potent chemotherapeutic agent, is marred by severe nephrotoxicity that is governed by mechanisms involving oxidative stress, inflammation, and apoptosis pathways. The transcription factor Nrf2, pivotal in cellular defense against oxidative stress and inflammation, is the master regulator of the antioxidant response, upregulating antioxidants and cytoprotective genes under oxidative stress. This review discusses the mechanisms underlying chemotherapy-induced kidney injury, focusing on the role of Nrf2 in cancer therapy and its redox regulation in cisplatin-induced kidney injury. We also explore Nrf2's signaling pathways, post-translational modifications, and its involvement in autophagy, as well as examine redox-based strategies for modulating Nrf2 in cisplatin-induced kidney injury while considering the limitations and potential off-target effects of Nrf2 modulation. Understanding the redox regulation of Nrf2 in cisplatin-induced kidney injury holds significant promise for developing novel therapeutic interventions. This knowledge could provide valuable insights into potential strategies for mitigating the nephrotoxicity associated with cisplatin, ultimately enhancing the safety and efficacy of cancer treatment
Aberrant planar cell polarity induced by urinary tract obstruction
Flow sensing by primary cilia of the epithelial cells is involved in cystogenesis in polycystic kidney disease. We investigate whether a similar mechanism applies to the pathogenesis of cyst-like tubular dilatation induced by ureteral obstruction in mice. Robust proliferation occurs in the obstructed tubules when urine flow is interrupted as well as in the repairing tubules when urine flow is reestablished after relief of the obstruction, suggesting a urine flow-independent mechanism of proliferation. In the urothelium, proliferation is only detected above the obstruction, although urine flow ceased both above and below the obstruction. Our results support mechanical strain- rather than flow-mediated proliferation in obstructive uropathy. To understand the mechanism of cell proliferation leading to increased tubular diameter in cyst-like tubular dilatation, we examine planar cell polarity (PCP), which is necessary for oriented cell division and maintenance of tubular diameter. In dilated tubules, the orientation of cell division is randomized, atypical PKC (aPKC) is mislocalized, and the pattern of the expression of a core PCP protein, Frizzled3 (Fz3), is altered. In addition, the level of Fz3 expression is increased. These results indicate that aberrant PCP may contribute to cyst-like tubular dilatation in obstructive uropathy. Interestingly, the orientation of cell division, localization of aPKC, and Fz3 expression return to normal when obstruction is relieved, which suggest a role of normal PCP signaling in tubular repair
Persistent increase in mitochondrial superoxide mediates cisplatin-induced chronic kidney disease
Severe and recurrent cisplatin-induced acute kidney injury (AKI) as part of standard cancer therapy is a known risk factor for development of chronic kidney disease (CKD). The specific role of superoxide (O2•-)-mediated disruption of mitochondrial oxidative metabolism in CKD after cisplatin treatment is unexplored. Cisplatin is typically administered in weekly or tri-weekly cycles as part of standard cancer therapy. To investigate the role of O2•- in predisposing patients to future renal injury and in CKD, mice were treated with cisplatin and a mitochondrial-specific, superoxide dismutase (SOD) mimetic, GC4419. Renal function, biomarkers of oxidative stress, mitochondrial oxidative metabolism, and kidney injury markers, as well as renal histology, were assessed to evaluate the cellular changes that occur one week and one month (CKD phase) after the cisplatin insult. Cisplatin treatment resulted in persistent upregulation of kidney injury markers, increased steady-state levels of O2•-, increased O2•--mediated renal tubules damage, and upregulation of mitochondrial electron transport chain (ETC) complex I activity both one week and one month following cisplatin treatment. Treatment with a novel, clinically relevant, small-molecule superoxide dismutase (SOD) mimetic, GC4419, restored mitochondrial ETC complex I activity to control levels without affecting complexes II–IV activity, as well as ameliorated cisplatin-induced kidney injury. These data support the hypothesis that increased mitochondrial O2•- following cisplatin administration, as a result of disruptions of mitochondrial metabolism, may be an important contributor to both AKI and CKD progression. Keywords: Cisplatin, Kidney injury, Mitochondrial metabolism, Superoxide, Superoxide dismutase mimeti
The antioxidant and anti-inflammatory activities of avasopasem manganese in age-associated, cisplatin-induced renal injury
Purpose: Cisplatin contributes to acute kidney injury (AKI) and chronic kidney disease (CKD) that occurs with greater frequency and severity in older patients. Age-associated cisplatin sensitivity in human fibroblasts involves increased mitochondrial superoxide produced by older donor cells. Experimental design: Young and old C57BL/6 J murine models of cisplatin-induced AKI and CKD were treated with the SOD mimetic avasopasem manganese to investigate the potential antioxidant and anti-inflammatory effects. Adverse event reporting from a phase 2 and a phase 3 randomized clinical trial (NCT02508389 and NCT03689712) conducted in patients treated with cisplatin and AVA was determined to have established the incidence and severity of AKI. Results: Cisplatin-induced AKI and CKD occurred in all mice, however, was more pronounced in older mice. AVA reduced cisplatin-induced mortality, AKI, and CKD, in older animals. AVA also alleviated cisplatin-induced alterations in mitochondrial electron transport chain (ETC) complex activities and NADPH Oxidase 4 (NOX4) and inhibited the increased levels of the inflammation markers, TNFα, IL1, ICAM-1, and VCAM-1. Analysis of age-stratified subjects treated with cisplatin from clinical trials (NCT02508389, NCT03689712) also supported that the incidence of AKI increased with age and AVA reduced age-associated therapy-induced adverse events (AE), including hypomagnesemia, increased creatinine, and AKI. Conclusions: Older mice and humans are more susceptible to cisplatin-induced kidney injury, and treatment with AVA mitigates age-associated damage. Mitochondrial ETC and NOX4 activities represent sources of superoxide production contributing to cisplatin-induced kidney injury, and pro-inflammatory cytokine production and endothelial dysfunction may also be increased by superoxide formation
Autophagy Is a Component of Epithelial Cell Fate in Obstructive Uropathy
Epithelial cell fate and nephron loss in obstructive uropathy are not fully understood. We produced transgenic mice in which epithelial cells in the nephrons and collecting ducts were labeled with enhanced yellow fluorescent protein, and tracked the fate of these cells following unilateral ureteral obstruction (UUO). UUO led to a decrease in the number of enhanced yellow fluorescent protein-expressing cells and down-regulation of epithelial markers, E-cadherin, and hepatocyte nuclear factor-1β. Following UUO, enhanced yellow fluorescent protein-positive cells were confined within the tubular basement membrane, were not found in the renal interstitium, and did not express α-smooth muscle actin or S100A4, markers of myofibroblasts and fibroblasts. Moreover, when proximal tubules were labeled with dextran before UUO, dextran-retaining cells did not migrate into the interstitium or express α-smooth muscle actin. These results indicate that UUO leads to tubular epithelial loss but does not cause epithelial-to-mesenchymal transition that has been shown by others to be responsible for nephron loss and interstitial fibrosis. For the first time, we found evidence of enhanced autophagy in obstructed tubules, including accumulation of autophagosomes, increased expression of Beclin 1, and increased conversion of microtubular-associated protein 1 light chain 3-I to -II. Increased autophagy may represent a mechanism of tubular survival or may contribute to excessive cell death and tubular atrophy after obstructive injury
Risk of COVID-19 after natural infection or vaccinationResearch in context
Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health