High-Altitude Medicinal Plants as Promising Source of Phytochemical Antioxidants to Combat Lifestyle-Associated Oxidative Stress-Induced Disorders.

Oxidative stress, driven by reactive oxygen, nitrogen, and sulphur species (ROS, RNS, RSS), poses a significant threat to cellular integrity and human health. Generated during mitochondrial respiration, inflammation, UV exposure and pollution, these species damage cells and contribute to pathologies like cardiovascular issues, neurodegeneration, cancer, and metabolic syndromes. Lifestyle factors exert a substantial influence on oxidative stress levels, with mitochondria emerging as pivotal players in ROS generation and cellular equilibrium.

Slit2/Robo1 signaling inhibits small-cell lung cancer by targeting β-catenin signaling in tumor cells and macrophages.

Small-cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with poor patient prognosis. However, the mechanisms that regulate SCLC progression and metastasis remain undefined. Here, we show that the expression of the slit guidance ligand 2 (SLIT2) tumor suppressor gene is reduced in SCLC tumors relative to adjacent normal tissue.

Cannabidiol Inhibits Tumorigenesis in Cisplatin-Resistant Non-Small Cell Lung Cancer via TRPV2.

Chemotherapy forms the backbone of current treatments for many patients with advanced non-small-cell lung cancer (NSCLC). However, the survival rate is low in these patients due to the development of drug resistance, including cisplatin resistance. In this study, we developed a novel strategy to combat the growth of cisplatin-resistant (CR) NSCLC cells.

Contribution of the tumor and obese microenvironment to triple negative breast cancer.

The growing burden of obesity and incidence of the aggressive triple negative breast cancer (TNBC) is a challenge, especially amongst vulnerable populations with unmet medical needs and higher mortality from breast cancer. While some mechanisms linking obesity and TNBC have been identified, the complex nature of pathogenesis, in both obesity as well as TNBC poses a real challenge in establishing a causative role of obesity in risk of TNBC. In this review article, we discuss pathological mechanisms identified in the tumor microenvironment (TME) as well as the obese microenvironment (OME), such as inflammation, insulin resistance and survival pathways that contribute to the development and progression of TNBC.

Macrophage migration inhibitory factor inhibition as a novel therapeutic approach against triple-negative breast cancer.

Triple-negative breast cancer (TNBC), defined as loss of estrogen, progesterone, and Her2 receptors, is a subtype of highly aggressive breast cancer with worse prognosis and poor survival rate. Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine aberrantly expressed in many solid tumors and known to promote tumor progression and metastasis. However, its role in TNBC progression and metastasis is unexplored.

Molecular and Cellular Factors Associated with Racial Disparity in Breast Cancer.

Recent studies have demonstrated that racial differences can influence breast cancer incidence and survival rate. African American (AA) women are at two to three fold higher risk for breast cancer than other ethnic groups. AA women with aggressive breast cancers show worse prognoses and higher mortality rates relative to Caucasian (CA) women.

Feasibility of a mindfulness-based cognitive therapy group intervention as an adjunctive treatment for postpartum depression and anxiety.

Background: Many women experience moderate-to-severe depression and anxiety in the postpartum period for which pharmacotherapy is often the first-line treatment. Many breastfeeding mothers are reticent to increase their dose or consider additional medication, despite incomplete response, due to potential adverse effects on their newborn. These mothers are amenable to non-pharmacological intervention for complete symptom remission.

Predictors of Recovery from Depression and Anxiety in Women: A Longitudinal Study from Childbirth to 6 Years.

Objective: This study prospectively examined maternal biopsychosocial predictors of recovery from comorbid depression and anxiety from 25 weeks' gestation to 6 years postbirth. Specifically, the study investigated the influence of 1) maternal factors and 2) the child's behaviours and physical health on the course of the mother's depressed mood and anxiety.

Methods: Eighty-six women diagnosed with antenatal depression/anxiety were recruited through the Reproductive Mental Health Program and family practices in Vancouver.

Overcoming functional impairment in postpartum depressed or anxious women: a pilot trial of desvenlafaxine with flexible dosing.

Objectives: Antidepressants are the first line treatment for moderate to severe major depressive disorder (MDD) in perinatal and general populations. However, there appears to be paucity of evidence around antidepressant use in women with postpartum depression or anxiety. Selection of an appropriate antidepressant is crucial in promoting efficacy, optimizing tolerability, and managing comorbid anxiety or depression.

Unique epigenetic influence of H2AX phosphorylation and H3K56 acetylation on normal stem cell radioresponses.

Normal tissue injury resulting from cancer radiotherapy is often associated with diminished regenerative capacity. We examined the relative radiosensitivity of normal stem cell populations compared with non-stem cells within several radiosensitive tissue niches and culture models. We found that these stem cells are highly radiosensitive, in contrast to their isogenic differentiated progeny.

Generalized Anxiety Disorder and Major Depressive Disorder in Pregnant and Postpartum Women: Maternal Quality of Life and Treatment Outcomes.

Objectives: Comorbid generalized anxiety disorder (GAD) and major depressive disorder (MDD) in perinatal women is often under-diagnosed, resulting in suboptimal treatment and leading to significant maternal dysfunction. We describe a prospective, longitudinal study of the course, treatment outcomes, and quality of life (QoL) in pregnant and postpartum women with MDD and anxiety disorders.

Methods: Two separate cohorts of women were recruited through the Reproductive Mental Health Program, Women's and Children's Hospital, Vancouver, British Columbia, for pharmacotherapy of depressed mood.

Perinatal Generalized Anxiety Disorder: Assessment and Treatment.

Perinatal generalized anxiety disorder (GAD) has a high prevalence of 8.5%-10.5% during pregnancy and 4.

Factors impacting decisions to decline or adhere to antidepressant medication in perinatal women with mood and anxiety disorders.

Purpose: To identify specific quantitative and qualitative factors that govern the decision to adhere or decline antidepressant medication in antenatal women with moderate-to-severe mood and anxiety disorders.

Methods: Fifty women (30 adherers, 20 decliners) were recruited between 18 and 34 weeks gestation in a tertiary care clinic for perinatal mothers. They were prospectively monitored 4 weeks apart up to 1-month postpartum on the: Hamilton Anxiety Scale, Hamilton Depression Scale, Mood Disorders Insight Scale, Antidepressant Compliance Questionnaire, Penn State Worry Questionnaire, and NEO Personality Inventory.

Biopsychosocial determinants of treatment outcome for mood and anxiety disorders up to 8 months postpartum.

Little is known about the biopsychosocial determinants that predict postpartum treatment outcome for mood and anxiety disorders. Postpartum mood and anxiety symptoms and psychosocial/biological variables were recorded for 8 months of 22 women treated with antidepressants during pregnancy. Depression scores decreased by 58%, whereas anxiety scores decreased by 35%.

Affect Expression and Self-Regulation Capacities of Infants Exposed in utero to Psychotropics.

This study explored the affect expression and self-regulation capacities of 8-month-old infants exposed in utero to psychotropic medications. This was a continuation of our previous study conducted on the same cohort when the infants were 3 months old. Psychotropics implicated included selective serotonin reuptake inhibitors (SSRIs), and a benzodiazepine derivative anxiolytic (clonazepam).

Prenatal effects of selective serotonin reuptake inhibitor antidepressants, serotonin transporter promoter genotype (SLC6A4), and maternal mood on child behavior at 3 years of age.

Objectives: To investigate whether prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure affects behavior in 3-year-olds of antenatally anxious or depressed mothers and whether risk was moderated by the serotonin transporter promoter (SLC6A4) genotype.

Design: Prospective longitudinal cohort design.

Setting: Vancouver.

Antenatal depression and anxiety affect postpartum parenting stress: a longitudinal, prospective study.

Objective: Postpartum depression has been associated with parenting stress, impacting attachment and child development. However, the relation between antenatal depression or anxiety and postpartum parenting stress has not been investigated. We studied the effect of antenatal depression and anxiety and treatment with selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors (antidepressants [ADs]) on postpartum parenting stress.

Caregiving behavior and interactions of prenatally depressed mothers (antidepressant-treated and non-antidepressant-treated) during newborn acute pain.

This exploratory study aimed to examine time-based measures of the behaviors and interactions of prenatally depressed serotonin reuptake inhibitors (SRI)-medicated mothers to their infant's pain (n = 10) by comparing them with similar measures obtained from prenatally depressed nonmedicated mothers and their infants (n = 10), and nondepressed mothers and their infants (n = 10). During the second trimester of their pregnancy, the 30 study mothers were assessed for depression and anxiety, with no further measures of maternal mood taken. Maternal and infant interactions were continuously videorecorded while the infant underwent a scheduled heel lance for routine blood screening that occurred when study infants were between the ages of 24 and 60 hr.

Cell cycle checkpoint defects contribute to genomic instability in PTEN deficient cells independent of DNA DSB repair.

Chromosomes in PTEN deficient cells display both numerical as well as structural alterations including regional amplification. We found that PTEN deficient cells displayed a normal DNA damage response (DDR) as evidenced by the ionizing radiation (IR)-induced phosphorylation of Ataxia Telangiectasia Mutated (ATM) as well as its effectors. PTEN deficient cells also had no defect in Rad51 expression or DNA damage repair kinetics post irradiation.

Detecting ATM-dependent chromatin modification in DNA damage and heat shock response.

The ataxia telangiectasia-mutated gene product (ATM), whose loss of function is responsible for ataxia telangiectasia (A-T), is a protein kinase that interacts with several substrates and is implicated in mitogenic signal transduction, chromosome condensation, meiotic recombination, cell-cycle control and telomere maintenance (Pandita, Expert Reviews in Molecular Medicine 5:1-21, 2003; Pandita, Oncogene 21:611-618, 2002; Matsuoka et al., Science 316:1160-1166, 2007). The ATM protein kinase is primarily activated in response to DNA double-strand breaks (DSBs) caused by ionizing radiation (IR) or radiomimetic drugs (Pandita et al.

Altered states of telomere deprotection and the two-stage mechanism of replicative aging.

The molecular distinctions between mortality stages 1 (M1; senescence) and 2 (M2; crisis) of human replicative aging are ill defined. We demonstrate a qualitative difference between telomeric end associations at M1 and the end fusions that produce dicentric chromosomes and breakage-fusion cycles. Knockdown of ligase IV sufficient to completely inhibit radiation-induced dicentric chromosome formation had no effect on the frequency of telomere associations (TAs), establishing that TAs are not covalent conventional nonhomologous end-joining (NHEJ) products.