Decoding contextual crosstalk: revealing distinct interactions between non-coding RNAs and unfolded protein response in breast cancer.

Breast cancer is significantly influenced by endoplasmic reticulum (ER) stress, impacting both its initiation and progression. When cells experience an accumulation of misfolded or unfolded proteins, they activate the unfolded protein response (UPR) to restore cellular balance. In breast cancer, the UPR is frequently triggered due to challenging conditions within tumors. The UPR has a dual impact on breast cancer. On one hand, it can contribute to tumor growth by enhancing cell survival and resistance to programmed cell death in unfavorable environments. On the other hand, prolonged and severe ER stress can trigger cell death mechanisms, limiting tumor progression. Furthermore, ER stress has been linked to the regulation of non-coding RNAs (ncRNAs) in breast cancer cells. These ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play essential roles in cancer development by influencing gene expression and cellular processes. An improved understanding of how ER stress and ncRNAs interact in breast cancer can potentially lead to new treatment approaches. Modifying specific ncRNAs involved in the ER stress response might interfere with cancer cell survival and induce cell death. Additionally, focusing on UPR-associated proteins that interact with ncRNAs could offer novel therapeutic possibilities. Therefore, this review provides a concise overview of the interconnection between ER stress and ncRNAs in breast cancer, elucidating the nuanced effects of the UPR on cell fate and emphasizing the regulatory roles of ncRNAs in breast cancer progression.

Bioactive peptides: an alternative therapeutic approach for cancer management.

Cancer is still considered a lethal disease worldwide and the patients' quality of life is affected by major side effects of the treatments including post-surgery complications, chemo-, and radiation therapy. Recently, new therapeutic approaches were considered globally for increasing conventional cancer therapy efficacy and decreasing the adverse effects. Bioactive peptides obtained from plant and animal sources have drawn increased attention because of their potential as complementary therapy. This review presents a contemporary examination of bioactive peptides derived from natural origins with demonstrated anticancer, ant invasion, and immunomodulation properties. For example, peptides derived from common beans, chickpeas, wheat germ, and mung beans exhibited antiproliferative and toxic effects on cancer cells, favoring cell cycle arrest and apoptosis. On the other hand, peptides from marine sources showed the potential for inhibiting tumor growth and metastasis. In this review we will discuss these data highlighting the potential befits of these approaches and the need of further investigations to fully characterize their potential in clinics.

Autoimmune thyroid disorders and polycystic ovary syndrome: Tracing links through systematic review and meta-analysis.

Polycystic Ovary Syndrome (PCOS) and Autoimmune Thyroiditis (AIT) are two prevalent endocrine disorders affecting women, often coexisting within the same patient population. This meta-analysis aims to systematically assess and synthesize the existing body of literature to elucidate the intricate relationship between PCOS and AIT. A systematic literature search for relevant observational studies was conducted in electronic databases such as Web of Science, Google Scholar, PubMed, Cochrane, and Scopus until March 2023. All Statistical analyses were performed using CMA Software v3.7 in a random-effects network meta-analysis. In addition, sensitivity and meta-regression analyses were conducted to identify sources of Heterogeneity based on related risk factors. Our meta-analysis included eighteen studies with 3657 participants, which revealed significant differences between PCOS patients and control groups. In particular, a considerable association was detected between PCOS and the presence of AIT (OR = 2.38; 95% CI: 1.63-3.49; P< 0.001) and elevated levels of TSH (SMD = 0.24; 95% CI: 0.06-0.42; P= 0.01), anti-TPO (SMD = 0.36; 95% CI: 0.19-0.53; P< 0.001), anti-TG (SMD = 1.24; 95% CI: 0.37-2.10; P< 0.001), and other positive serum antibodies compared to the control groups. The findings from this meta-analysis may contribute to enhanced diagnostic strategies like complete thyroid function tests, more targeted interventions, and improved patient care for individuals presenting with both PCOS and AIT. Additionally, identifying commonalities between these conditions may pave the way for future research directions, guiding the development of novel therapeutic approaches that address the interconnected nature of PCOS and AIT.

A higher number of exhausted local PD1+, but not TIM3+, NK cells in advanced endometriosis.

Endometriosis (EMT) is a chronic inflammatory disease characterized by the presence and growth of endometrial-like glandular epithelial and stromal cells outside the uterus. Natural Killer (NK) cell dysfunction/exhaustion has been shown in patients with EMT. In this case-control study, we compared the frequency of exhausted PD-1 or TIM-3 positive NK cells in peripheral blood (PB) and peritoneal fluid (PF) of women with advanced endometriosis to control fertile women. PB and PF were collected from women aged 25-40 who underwent the laparoscopic procedure, including 13 stages III/IV endometriosis and 13 control samples. Multicolor flowcytometry was used to compare the frequency of PD-1 or TIM-3 positive NK (CD3-CD56+) cells in PB and PF of two groups. We demonstrated a higher percentage of PD-1+ NK cells in the peritoneal fluid of patients with endometriosis rather than controls (P-value = 0.039). This significance was related to stage IV of endometriosis (P-value = 0.047). We can not show any significant difference in the number of PD-1 or TIM-3 positive NK cells in peripheral blood. Our results suggest a local exhausted NK cell response in endometriosis that can be a leading factor in the endometriosis pathogenesis.

Reduced expression of Il10, Stat3, Hoxa10, and Itgb3 in the embryo implantation site of rat model with prenatal androgen-induced polycystic ovary syndrome.

AIMS: Impaired implantation due to the reduced endometrial receptivity considers an etiology for infertility in polycystic ovary syndrome (PCOS). In this context, we aimed to compare the expression of interleukin 10 (Il10), homeobox A10 (Hoxa10), signal transducer and activator of transcription 3 (Stat3), and ß3-integrin (Itgb3) in the embryo implantation site of a prenatally-androgenized rat model of PCOS before and during gestation. MATERIALS AND METHODS: PCOS rat model was created by the injection of testosterone prenatally. The uterine tissues were collected before pregnancy (day 0) and on days 0.5, 4.5, 5.5, and 8.5 of gestation in the PCOS rat model and controls (n = 6; each group). RNA was extracted from the uterine samples and reverse transcribed to cDNA. Expression levels of Il10, Stat3, Hoxa10, and Itgb3 were measured using SYBR Green real-time RT-PCR and compared between the two groups. FINDINGS: PCOS rats showed decreased expression levels of the Il10 on day 8.5 compared to control rats. The mRNA levels of Hoxa10, Itgb3, and Stat3 were significantly decreased in the PCOS group on day 0 as well as on days 0.5, 4.5, 5.5, and 8.5 for Hoxa10, Itgb3, and Stat3. SIGNIFICANCE: The decreased gene expression of Il10, Hoxa10, Stat3, and Itgb3 in the PCOS rat model indicates the importance of the Il10 signaling axis as one of the possible disrupted mechanisms of endometrial receptivity in PCOS.

Altered expression of leukemia inhibitory factor (LIF), LIFR, gp130, and IL11 in the embryo implantation site of rat model with prenatal androgen-induced polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that represents infertility in many reproductive-age women. Reduced implantation of blastocyst was proposed as an etiology for infertility in this syndrome. In this regard, many candidate genes such as leukemia inhibitory factor (LIF), LIF receptor (LIFR), glycoprotein 130 (gp130), and interleukin 11 (IL11) were proposed to be disrupted. Investigation of these genes is not ethically approved in pregnant women with PCOS. In this study, we aimed to compare the expression of LIF, LIFR, gp130, and IL11 before and during different gestational days in uterine tissues of prenatally-androgenized rat models of PCOS with control rats. The rat model of polycystic ovary syndrome was created by the injection of testosterone during prenatal life. RNA extraction and cDNA synthesis from uterine tissues were performed in both prenatal induced PCOS and control rats. Expression of LIF, LIFR, gp130, and IL11 genes was compared before pregnancy (GD0) and during pregnancy on GD0.5, GD4.5, GD5.5, and GD8.5 between two study groups (n = 6 each group) using SYBR Green real-time PCR. The expression of the LIF mRNAs significantly decreased on GD4.5, 5.5, and 8.5 in the PCOS rats compared to the controls (P-values: 0.0483, 0.0152, and 0.0043). Additionally, decreased expression of LIFR and gp130 was observed on GD0.5 to 8.5 in PCOS rats compared to controls (P-values: 0.022, 0.0480, 0.0043, 0.0022 for LIFR and 0.0189, 0.0022, 0.0087, 0.0022 for gp130). Moreover, IL-11 mRNA levels decreased in the PCOS group compared to their controls both before (P-value:0.0362) and during the gestational period (P-values:0.0085, 0.0043, 0.0389, 0.0087). Reduced expression of LIF, LIFR, gp130, and IL11 in the rats with PCOS indicates a possible disruption in the implantation and decidualization stages in this syndrome.

Redox imbalance in Crohn's disease patients is modulated by Azathioprine.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease without a specific cause. Inflammation in these patients can disturb the oxidants/antioxidants balance and results in oxidative stress that plays a destructive role. This study aimed to evaluate the gene expression of sod1, sod2, cat, nrf2 and gp91phox in CD patients before and after Azathioprine (Aza) consumption. METHOD: Peripheral bloodmononuclear cells (PBMCs) were separated from CD patients (n= 15, mean age = 33.6 ± 1.8) before and after treatment with Aza and healthy controls (n= 15, mean age = 31.5 ± 1.2). The expression levels of sod1, sod2, cat, nrf2 and gp91phox were measured in byusing real-time qRT-PCR technique. RESULT: The expression levels of gp91phox (P-value < 0.001), cat (P-value < 0.05), sod1 (P-value < 0.001), nrf2 (P-value < 0.001) were significantly increased compared to control group. Following treatment with Aza, the decreased expression levels of gp91phox (P-value < 0.05), cat (P-value < 0.05), sod1(P-value < 0.001) and nrf2 (P-value < 0.001) were observed in CD patients. CONCLUSION: Overall, our results showed that prescription of Azathioprine can lead to the altered expression of redox system-related genes in patients with CD.