Introduction: Alzheimerʼs disease (AD) has been identified as a progressive memory and cognitive impairment. Some Salvia species are suggested by certain studies for the management of mild to moderate AD. We aimed to evaluate the anti-inflammatory, antioxidant, and anti-apoptotic effects of S. hydrangea on amyloid beta-injected rats. Materials and Methods: Rats were pretreated with S. hydrangea for 10 days before amyloid beta (Aβ) injection. Western blotting techniques were used to evaluate protein level of γ-glutamyl cysteine synthetase (γ-GCS), Tumor Necrosis Factor α (TNF-α) and Interleukin-6 (IL-6) in two brain regions: hippocampus and frontal cortex. Results: Current data show that S. hydrangea extract increased γ-GCS protein levels in amyloid beta injected rats, and pretreatment with S. hydrangea increased it further. Besides, S. hydrangea decreased protein levels of TNF-α and IL-6 in amyloid beta injected rats. Conclusion: Based on the decreased levels of IL-6, TNF-α, and the increased levels of γ-GCS, it is suggested that the use of S. hydrangea could be protective in neurodegenerative diseases.

Amino acids (AAs) and vitamin imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFβ in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. The plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p = 0.04) and an increase in IL-2 (p = 0.008) and IL-12 (p = 0.007) mRNA expression compared to the HCs. The treated adult patients showed elevated Serine (p = 0.003) and Glycine (p = 0.04) levels, as well as increased IL-12 (p < 0.0001) mRNA expression, and a decrease in Tryptophan (p = 0.04) levels relative to the controls. Additionally, the treated adult patients had higher plasma levels of Threonine compared to both the active (p = 0.04) and control (p = 0.02) subjects, and the increased mRNA expression of IL-4 (p = 0.01) in comparison to the active patients. In active children with CD, the IL-2 mRNA level was found to be higher than in the controls (p < 0.0001) and in the treated children (p = 0.005). The treated children with CD exhibited decreased plasma levels of Tryptophan (p = 0.01) and Isoleucine (p = 0.01) relative to the controls, and the increased mRNA expression of TGFβ (p = 0.04) relative to the active patients. Elevated levels of specific AAs (Serine, Glycine, Threonine) in the treated CD patients suggested their potential to improve intestinal damage and inflammation, while decreased levels of Tryptophan and Isoleucine highlighted the need for dietary intervention.

The amino acids (AAs) and vitamins imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFβ in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. Plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p=0.04) and an increase in IL-2 (p=0.008) and IL-12 (p=0.007) mRNA expression compared to HCs. Treated adult patients showed elevated Serine (p=0.003) and Glycin (p=0.04) levels, as well as increased IL-12 (P<0.0001) mRNA expression, and a decrease in Tryptophan (p=0.04) levels relative to the controls. Additionally, treated adult patients had higher plasma levels of Threonine compared to both active (p=0.04) and control (p=0.02) subjects, and increased mRNA expression of IL-4 (p=0.01) in comparison to active patients. In active children with CD, IL-2 mRNA level was found to be higher than in controls (P<0.0001) and in treated children (p=0.005). Treated children with CD exhibited decreased plasma levels of Tryptophan (p=0.01) and Isoleucine (p=0.01) relative to the controls, and increased mRNA expression of TGFβ (p=0.04) relative to active patients. Managing Retinoic acid levels is crucial to alleviate intestinal inflammation of CD patients. Threonine, tryptophan, and Isoleucine are potential therapeutic options for treating CD, and targeting serine, histidine, tyrosine, and aspartate may hold promise as therapeutic targets for CD patients.

Celiac disease (CD) is a hereditary immune-mediated disorder, which is along with the enormous production of pro-inflammatory cytokines and the reduced level of tight junction proteins. The aim of this study was to determine the expression of TNF-α, IFN-γ, IL-18, Occludin, miR-122-5p and miR-197-3p genes in duodenal biopsies of treated CD patients in comparison to the controls. Biopsy specimens were taken from the duodenum of 50 treated CD patients (36 (72

Epigenetic factors are critical regulators of biological and pathological mechanisms and they could interact with different molecular pathways. Targeting epigenetic factors has been an idea approach in disease therapy, especially cancer. Accumulating evidence has highlighted function of long non-coding RNAs (lncRNAs) as epigenetic factors in cancer initiation and development and has focused on their association with downstream targets. microRNAs (miRNAs) are the most well-known targets of lncRNAs and present review focuses on lncRNA-miRNA axis in malignancy and therapy resistance of tumors. LncRNA-miRNA regulates cell death mechanisms such as apoptosis and autophagy in cancers. This axis affects tumor metastasis via regulating EMT and MMPs. Besides, lncRNA-miRNA axis determines sensitivity of tumor cells to chemotherapy, radiotherapy and immunotherapy. Based on the studies, lncRNAs can be affected by drugs and genetic tools in cancer therapy and this may affect expression level of miRNAs as their downstream targets, leading to cancer suppression/progression. LncRNAs have both tumor-promoting and tumor-suppressor functions in cancer and this unique function of lncRNAs has complicated their implication in tumor therapy. LncRNA-miRNA axis can also affect other signaling networks in cancer such as PI3K/Akt, STAT3, Wnt/β-catenin and EZH2 among others. Notably, lncRNA/miRNA axis can be considered as a signature for diagnosis and prognosis in cancers.

One of the malignant tumors in women that has involved both developed and developing countries is breast cancer. Similar to other types of tumors, breast cancer cells demonstrate high metastatic nature. Besides, breast tumor cells have ability of developing drug resistance. EMT is the related mechanism to cancer metastasis and focus of current manuscript is highlighting function of EMT in breast tumor malignancy and drug resistance. Breast tumor cells increase their migration by EMT induction During EMT, N-cadherin and vimentin levels in-crease, and E-cadherin levels decrease to mediate EMT-induced breast tumor invasion. Different kinds of anti-cancer agents such as tamoxifen, cisplatin and paclitaxel that EMT induction mediates chemoresistance feature of breast tumor cells. Furthermore, EMT induction correlates with radio-resistance in breast tumor. Clinical aspect is reversing EMT in preventing chemotherapy or radiotherapy failure in breast cancer patients and improving their survival time. The anti-tumor agents that suppress EMT can be used for decreasing breast cancer invasion and increasing chemosensitivity of tumor cells. Furthermore, lncRNAs, miRNAs and other factors can modulate EMT in breast tumor progression that are discussed here.

Introduction: Nuclear factor, erythroid-derived 2, -like2 (Nrf2) and Nuclear erythroid 2-related factor 1 (Nrf1) stand as two important regulators of antioxidant defense system.Materials and Methods: Small interfering RNA (siRNA) targeting Nrf1 and Nrf2 (Nrf1&2) was injected in dorsal third ventricle of adult male albino Wistar rats. Anxiety-related behaviors and protein level of mitochondrial biogenesis, apoptotic marker factors and also electron transport chain (ETC), Citrate synthase (CS) and Malate dehydrogenase (MDH) enzymes activity in three brain regions: hippocampus, prefrontal cortex, and amygdala were evaluated.Results: Nrf1&2-silenced rats induced anxiety-like behaviors compared to the control group. The level of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) protein increased in those three regions. Although Nrf1&2-silencing decreased MDH activity in hippocampus and prefrontal cortex, the activity of CS was increased in all three mentioned areas. However, Nrf1&2 silencing had no effect in complex I and II-III activity, but complex IV activity was increased, particularly in amygdala. Furthermore, Bax/Bcl2 ratio and cleavage of caspase-3 was increased in all mentioned areas of the brain in Nrf1&2-silenced group.Conclusion: In conclusion, the presented data evaluated the complexity of mitochondrial functions and Nrf1 and Nrf2 in rat’s brain and points to mitochondrial crucial role in oxidative stress, energy metabolism, and behavior.