Influence of Ultrasonication and UV-C Processing on the Functional Characteristics and Anticarcinogenic Activity of Blackthorn Vinegar.

In recent years, consumer trends have been changing toward fresh food products such as fruit juice, vinegar, etc. that are a good source of bioactive components, high nutritional characteristics, and beneficial microorganisms. Blackthorn (Prunus spinosa L.) vinegar (BV) is one of these nutritious foods. The study aims to examine the efficacy of ultraviolet-C (UV-C) light applied by a modified reactor and ultrasonication on bioactive compounds (total phenolic, total flavonoid, ascorbic acid content, and antioxidant activity) of traditionally produced BV. Furthermore, the volatile organic compound (VOC) profile, hydroxymethylfurfural (HMF) content, cytotoxicity properties, and color were assessed. UV-C light and ultrasonication processes enriched most bioactive components, but these methods did not significantly improve ascorbic acid (p > 0.05) compared to pasteurization. Twenty-seven volatile compounds were analyzed in order to determine the VOC profile. As a result, thermal and nonthermal methods were found to affect the profile significantly (p < 0.05). No significant differences were detected in total soluble solids (4.70-4.77), titratable acidity (3.81-3.87), and pH (3.39-3.41) values. The anticarcinogenic activities of UV-C-treated BVs were more significant than others. Nonthermal treatments were generally better than pasteurization in maintaining and enriching the quality of BV. In this study, UV-C light and ultrasonication technology can be used as an alternative to traditional thermal techniques to improve the quality of BV.

Bioactive, Pro-Apoptotic-Angiotensin Converting Enzyme Inhibitor Effects and Properties of Ultrasound-Treated Traditional Poppy Vinegar Using the Response Surface Methodology Model.

Poppy vinegar with functional properties is a fermented product. This study evaluated traditionally produced poppy vinegar. The study was conducted on poppy vinegar to determine the maximum increase in angiotensin converting enzyme (ACE) inhibitory activity %, total phenolic content (TPC), and radical scavenging activity (DPPH) of the vinegar at different combinations of ultrasound treatment duration (2-14 min) and amplitude (40-100%). The optimal parameters obtained using the response surface methodologies (RSM) were the duration of the ultrasound of 5.5 min and the amplitude of the ultrasound at 57%. When the DPPH values, ACE inhibition %, and TPC and DPPH values obtained with the RSM model were compared with the experimental values, the difference was 9.80, 3.0, and 4.6%, respectively, showing good agreement between actual and predicted values. The higher ultrasound intensities and longer treatment times had a significant effect on antioxidant activity. Poppy vinegar samples significantly induced the apoptosis of lung cancer cells, particularly those stored for 6 and 12 months. The amounts of protocatechuic acid, gallic acid, neohesperidin, hydroxybenzoic acid, resveratrol, rutin, trans-cinnamic acid, quercetin, and flavon in poppy vinegar were determined, which decreased significantly as storage time increased. TPC and TFC were determined to be 90.39 mg of GAE/100 mL and 29.86 mg of TEAC/mL, respectively, and there was no significant change in these bioactive compounds after 6 months of storage. The highest value of ACE inhibitory activity was found at the beginning of the storage period. The present study was the first study to examine the bioactive components, ACE inhibition activity, pro-apoptotic activities, and phenolic composition of traditionally produced ultrasound-treated poppy vinegar during storage. The control of production parameters and the design of ideal poppy vinegar fermentation processes could benefit from this research.

The fate and function of non-coding RNAs during necroptosis.

Necroptosis is a novel form of cell death which is activated when apoptotic cell death signals are disrupted. Accumulating body of observations suggests that noncoding RNAs, which are the lately discovered mystery of the human genome, are significantly associated with necroptotic signaling circuitry. The fate and function of miRNAs have been well documented in human disease, especially cancer. Recently, lncRNAs have gained much attention due to their diverse regulatory functions. Although available studies are currently based on bioinformatic analysis, predicted interactions desires further attention, as these hold significant promise and should not be overlooked. In the light of these, here we comprehensively review and discuss noncoding RNA molecules that play significant roles during execution of necroptotic cell death.

Necroptosis is a novel form of cell death triggered by disrupted apoptotic signals. noncoding RNAs, a mystery of the human genome, are significantly associated with necroptotic signaling. Their diverse regulatory functions, particularly in cancer, warrant further attention due to their potential.

Identification of non-coding RNA signatures in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a deadly, chronic, progressive, irreversible interstitial lung disease characterized by the formation of scar tissue resulting in permanent lung damage. The average survival time following diagnosis is only 3-5 years, with a 5-year survival rate shorter than that of many cancers. Alveolar epithelial cell injury followed by irregular repair is the primary pathological process observed in patients with IPF. An evident characteristic of IPF is the development of fibroblastic foci representing active fibrotic areas. Most of the cells within these foci are believed to be myofibroblasts, which are thought to be the primary source of abnormal extracellular matrix production in IPF. The lung phenotype in IPF is characterized by significantly different processes from healthy lungs, including irregular apoptosis, oxidative stress, and epithelial-mesenchymal transition (EMT) pathways. AIMS: The exact cause of IPF is not fully understood and remains mysterious. It is not suppressing that non-coding RNAs are involved in the development and progression of IPF. Accordingly, here we aimed to identify non-coding RNA molecules during TGFß-induced myofibroblast activation. METHODS: Differential expression and functional enrichment analysis were employed to reveal the impact of non-coding RNAs during TGFß-associated lung fibrosis. RESULTS: Remarkably, LOC101448202, CZ1P-ASNS, LINC01503, IER3-AS1, MIR503HG, CLMAT3, LINC02593, ACTA2-AS1, LOC102723692, LOC107985728, and LOC105371064 were identified to be differentially altered during TGFß-stimulated myofibroblast activation. CONCLUSIONS: These findings strongly suggest that the mechanism of lung fibrosis is heavily under control of non-coding RNAs, and RNA-based therapies could be a promising approach for future therapeutic interventions to lung fibrosis.

1,3-Diaryl Triazenes Incorporating Disulfonamides Show Both Antiproliferative Activity and Effective Inhibition of Tumor-associated Carbonic Anhydrases IX and XII.

AIM: The aim of this study was to synthesize a library of novel di-sulfa drugs containing 1,3- diaryltriazene derivatives TS (1-13) by conjugation of diazonium salts of primary sulfonamides with sulfa drugs to investigate the cytotoxic effect of these new compounds in different cancer types and to determine their inhibitory activity against tumor-associated carbonic anhydrases IX and XII. MATERIALS AND METHODS: A carbonic anhydrase inhibitory activity of the obtained compounds was evaluated against four selected human carbonic anhydrase isoforms (hCA I, hCA II, hCA IX and hCA XII) by a stoppedflow CO2 hydrase assay. In addition, in vitro, cytotoxicity studies were applied by using A549 (lung cancer), BEAS-2B (normal lung), MCF-7 (breast cancer), MDA-MB-231 (breast cancer), CRL-4010 (normal breast epithelium), HT-29 (colon cancer), and HCT -116 (colon cancer) cell lines. RESULTS: As a result of the inhibition data, the 4-aminobenzenesulfonamide derivatives were more active than their 3-aminobenzenesulfonamide counterparts. More specifically, compounds TS-1 and TS-2, both of which have primary sulfonamides on both sides of the triazene linker, showed the best inhibitory activity against hCA IX with Ki values of 19.5 and 13.7 nM and also against hCA XII with Ki values of 6.6 and 8.3 nM, respectively. In addition, in vitro cytotoxic activity on the human breast cancer cell line MCF-7 showed that some derivatives of di-sulfa triazenes, such as TS-5 and TS-13, were more active than SLC-0111. CONCLUSION: With the aim of developing more potent and isoform-selective CA inhibitors, these novel hybrid molecules containing sulfa drugs, triazene linkers, and the classical primary sulfonamide chemotype may be considered an interesting example of effective enzyme inhibitors and important anticancer agents.

Long non-coding RNA signatures in non-small cell lung cancer and their clinicopathological significance.

Lung cancer is the most common type of cancer in our country and worldwide, and it is a leading cause of cancer-related deaths. According to the latest global cancer statistics, lung cancer was identified as the second most common type of cancer, and the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) are a highly heterogeneous class of RNA molecules sharing many characteristics with mRNAs, except for the protein-coding potential. Accumulating mass of evidence suggest that lncRNAs play key regulatory roles during the multistep formation of human cancers including lung cancer. In previous studies, it has been shown that many lncRNA molecules play significant roles in the formation and progression of lung cancer. However, there are still numerous lncRNA molecules in lung cancer whose roles remain unknown. Accordingly, here we sought to ascertain the diagnostic and prognostic value of lncRNAs by analyzing the expression profiles of THRIL, NEAT1, and LOC105376095 in lung cancer. Remarkably, NEAT1 and LOC105376095 but not THRIL were identified to be differentially expressed in tissues of lung tumors. More importantly, LOC105376095, a yet uncharacterized lncRNA molecule, was significantly associated with the disease severity. Collectively, NEAT1 and LOC105376095 hold promise as potential diagnostic and prognostic biomarkers for lung cancer, presenting opportunities for targeted therapeutic interventions in the future.

The Role and Antagonistic Effects of miR-16-5p in the Regulation of ADP-Ribosylation Factor-Like Tumor Suppressor Gene 1 in Lung Cancer Cells.

OBJECTIVE: ADP-ribosylation factor-like tumor suppressor gene 1 is a member of the Ras superfamily of small guanosine triphosphatases that are known to be involved in multiple regulatory pathways in the multistage development of human cancers. Also, ADP-ribosylation factor-like tumor suppressor gene 1 expression levels have been reported to be dramatically lower in both cancer cell lines and tumor tissues compared to controls. Accordingly, defects in the regulation of the ADP-ribosylation factor-like tumor suppressor gene 1 gene seems have key tumor suppressive effects in the formation and development of human cancers including lung cancer. Moreover, microRNAs regulating the expression of ADP-ribosylation factor-like tumor suppressor gene 1 have not been described previously. Accordingly, the present study aimed to reveal the influence of miR-16-5p on the regulation of ADP-ribosylation factor-like tumor suppressor gene 1 gene. MATERIALS AND METHODS: A549 lung adenocarcinoma cells were used. For the overexpression and silencing experiments of miR-16-5p synthetic microRNA mimics and inhibitors were used, respectively. Gene expression analyses were achieved with the help of quantitative real-time polymerase chain reaction. RESULTS: MiR-16-5p was identified to be predictive target of ADP-ribosylation factor-like tumor suppressor gene 1 and directly targets the expression of ADP-ribosylation factor-like tumor suppressor gene 1 as revealed by the overexpression and silencing experiments. Specifically, it was found that miR-16-5p-overexpressed A549 cells showed a decrease in ADP-ribosylation factor-like tumor suppressor gene 1 gene expression, whereas miR16-5p-suppressed cells showed an increase in expression. These findings possibly suggest that miR-16-5p is the direct regulatory microRNA that posttranscriptionally regulates the expression of ADP-ribosylation factor-like tumor suppressor gene 1. CONCLUSION: Collectively, miR-16-5p seems to be a key regulatory molecule involved in the posttranscriptional regulation of the ADP-ribosylation factor-like tumor suppressor gene 1, and it might be responsible for the downregulation of this gene in lung cancer.

Unveiling the therapeutic potential of natural-based anticancer compounds inducing non-canonical cell death mechanisms.

In the Mid-19th century, Rudolf Virchow considered necrosis to be a prominent form of cell death; since then, pathologists have recognized necrosis as both a cause and a consequence of disease. About a century later, the mechanism of apoptosis, another form of cell death, was discovered, and we now know that this process is regulated by several molecular mechanisms that "programme" the cell to die. However, discoveries on cell death mechanisms are not limited to these, and recent studies have allowed the identification of novel cell death pathways that can be molecularly distinguished from necrotic and apoptotic cell death mechanisms. Moreover, the main goal of current cancer therapy is to discover and develop drugs that target apoptosis. However, resistance to chemotherapeutic agents targeting apoptosis is mainly responsible for the failure of clinical therapy and adverse side effects of the chemotherapeutic agents currently in use pose a major threat to the well-being and lives of patients. Therefore, the development of natural-based anticancer drugs with low cellular and organismal side effects is of great interest. In this comprehensive review, we thoroughly examine and discuss natural anticancer compounds that specifically target non-canonical cell death mechanisms.

Inflammation-associated long non-coding RNA signature in radicular cyst tissues.

Radicular cysts are characterized by significant levels of changes in inflammatory biomarkers. Among them, interleukins and growth factors have been reported to be deregulated in radicular cyst tissues. Moreover, long non-coding RNAs are recently discovered non-coding RNA molecules that regulate various intracellular stimuli to keep homeostasis in balance. A growing body of evidence suggests that lncRNAs are significantly involved in the regulation of inflammation by targeting various inflammatory biomarkers. Accordingly, the present study was aimed to investigate the gene expression levels of inflammation-related lncRNAs in radicular cysts and show their possible roles in the development of radicular cysts. For the study, a total of 25 patients with a radiologically and pathologically confirmed radicular cyst were enrolled. For the determination of non-coding RNA expression levels, real-time qPCR was used. As a result of the current study, expression levels of PACER and THRIL were found to be significantly elevated in radicular cyst tissues compared to control tissue samples. However, MALAT1, ANRIL, and NEAT1 expression levels were not significantly altered in radicular cyst tissues compared to control tissue samples. In conclusion, long non-coding RNAs, PACER and THRIL, seem to have significant pathophysiological roles by acquiring molecular changes during inflammation and might be involved in the development and formation of radicular cysts.

The roles of long non-coding RNAs in the necroptotic signaling of colon cancer cells.

BACKGROUND: Necroptosis is a controlled form of necrosis which can be stimulated in cases where the apoptosis signal is absent. Necroptosis can be induced by DR family ligands and by various intracellular and extracellular stimuli that triggers the activation of DR family ligands. Necrostatins, which are specific RIP1 antagonists, prevent necroptosis by inhibiting RIP1 kinase, allowing survival and propagation of cells in the presence of DR ligands. Furthermore, there is a mounting evidence that long non-coding RNA (lncRNA) molecules accomplish vital functions in cell death processes such as apoptosis, autophagy, pyroptosis, and necroptosis. Accordingly, here we aimed to decipher the lncRNAs that are involved in the control and maintenance of necroptosis signaling. METHODS AND RESULTS: Colon cancer cell lines, HT-29 and HCT-116 were used for the study. For the chemical modulation of necroptosis signaling, 5-Fluorouracil, TNF-α and/or Necrostatin-1 were used. Gene expression levels were determined by quantitative real-time PCR. Remarkably, lncRNA P50-associated COX-2 extragenic RNA (PACER) was identified to be suppressed in necroptosis-induced colon cancers, whereas the expression of PACER was restored when necroptosis was suppressed. In addition, no detectable change was observed in HCT-116 colon cancer cells, as these cells lack the expression of RIP3 kinase. CONCLUSIONS: Collectively, current findings clearly imply that PACER have key regulatory roles in the control of necroptotic cell death signaling circuitry. Notably, the tumor promoter activity of PACER might be responsible for the lack of necroptotic death signal in cancer cells. Also, RIP3 kinase seems to be essential component in PACER-associated necroptosis.

Variations in genomic regions encoding long non-coding RNA genes associated with increased prostate cancer risk.

From a single restriction fragment length polymorphism analysis to next generation sequencing analysis that screens the entire human genome, testing for genomic variations provides a great and robust approach to cancer testing. Non-coding RNAs have been shown to have a major impact on the development and progression of human cancers, including prostate cancer. However, the low stability of these molecules under laboratory conditions has made their clinical utility challenging, as in the case of PCA3 long non-coding RNA. Since testing for variations in genomic regions encoding non-coding RNAs offers a promising approach for cancer testing, identification and interpretation of single nucleotide polymorphisms associated with prostate cancer susceptibility is of great interest. Accordingly, here, for the first time, we review and discuss current available knowledge about genomic variation of long non-coding RNA molecules in prostate cancer.

Emerging role of microRNAs and long non-coding RNAs in COVID-19 with implications to therapeutics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which is commonly known as COVID-19 (COronaVIrus Disease 2019) has creeped into the human population taking tolls of life and causing tremendous economic crisis. It is indeed crucial to gain knowledge about their characteristics and interactions with human host cells. It has been shown that the majority of our genome consists of non-coding RNAs. Non-coding RNAs including micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs) display significant roles in regulating gene expression in almost all cancers and viral diseases. It is intriguing that miRNAs and lncRNAs remarkably regulate the function and expression of major immune components of SARS-CoV-2. MiRNAs act via RNA interference mechanism in which they bind to the complementary sequences of the viral RNA strand, inducing the formation of silencing complex that eventually degrades or inhibits the viral RNA and viral protein expression. LncRNAs have been extensively shown to regulate gene expression in cytokine storm and thus emerges as a critical target for COVID-19 treatment. These lncRNAs also act as competing endogenous RNAs (ceRNAs) by sponging miRNAs and thus affecting the expression of downstream targets during SARS-CoV-2 infection. In this review, we extensively discuss the role of miRNAs and lncRNAs, describe their mechanism of action and their different interacting human targets cells during SARS-CoV-2 infection. Finally, we discuss possible ways how an interference with their molecular function could be exploited for new therapies against SARS-CoV-2.

Expression pattern of hypoxia-related genes in odontogenic cysts.

OBJECTIVE: The aim of the present study was to reveal the effects of hypoxia-associated signaling in odontogenic cysts. DESIGN: The expression levels of genes involved in the hypoxia-associated signaling pathway were determined by quantitative Polymerase Chain Reaction (PCR) method. RESULTS: As a result, it was found that phosphatase and tensin homolog (PTEN) expression was low (p = 0.037), and the expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (p = 0.0127), hypoxia inducible factor 1 alpha (HIF1A) (p < 0.001), and HIF1A antisense RNA 1 (HIF1A-AS1) (p = 0.0218) were higher in cyst tissue compared to normal tissue. HIF1A gene expression was found to be significantly altered according to the pathologic subtypes of odontogenic keratocyst, dentigerous cyst, and radicular cyst. CONCLUSIONS: Odontogenic cysts were found to have higher expression of HIF1A and HIF1A-AS1, which may be related to the increased hypoxia in these lesions. In addition, PI3K/Akt signaling may be stimulated by increased PIK3CA and decreased PTEN expression, which promote cell survival and support the mechanism of cyst formation.

Non-coding RNA variations in oral cancers: A comprehensive review.

For a long time, scientists believed that only changes or mutations in protein-coding genes were responsible for the onset and development of cancer. However, the discovery of non-coding RNAs has revolutionized our understanding of tumor biology. Now, we are aware that non-coding RNA molecules have a higher influence on cancer biology than previously thought. The discovery of non-coding RNAs also presented several challenges because they are relatively unstable under laboratory conditions and can lead to false-positive and false-negative results in expression analysis. Therefore, variation analysis may provide more accurate results for understanding the role and impact of these molecules in cancer biology. Accordingly, in the present comprehensive review, we aimed to review and discuss current knowledge on non-coding RNA alterations linked to the development and progression of oral malignancies. Collectively, variations of non-coding RNA molecules seem to have great impact in the development and progression of oral cancers.

Novel zinc oxide nanoparticles of Teucrium polium suppress the malignant progression of gastric cancer cells through modulating apoptotic signaling pathways and epithelial to mesenchymal transition.

Management of gastric cancer is still challenging due to resistance to current chemotherapeutics and recurrent disease. Moreover, green- synthesized zinc oxide nanoparticles (ZnO-NPs) using natural resources are one of the most promising therapeutic agents for anticancer therapy. Here we report the facile green synthesis and characterization of ZnO-NPs from Teucrium polium (TP-ZnO-NP) herb extract and the anticancer activities of these nanoparticles on gastric cancer cells. Facile green synthesis of TP-ZnO-NP was achieved using zinc acetate dihydrate. For the characterization of TP-ZnO-NP, UV-vis spectroscopy, FTIR, SEM, XRD and EDX analyses were performed. Antiproliferative and anticancer activities of TP-ZnO-NP were explored using the HGC-27 gastric cancer cell line model. MTT cell viability and colony formation assays were used for the analysis of cell proliferation and migration. Wound healing assay was used to analyze the migration capacities of cells. Annexin V/PI double staining, DNA ladder assay, and Acridine orange/Ethidium bromide staining were performed to analyze the induction of apoptosis. qPCR was used to determine gene expression levels of apoptotic and epithelial to mesenchymal transition marker genes. The aqueous extract of TP served as both a reducing and capping agent for the successful biosynthesis of zinc oxide nanoparticles. Remarkably, synthesized TP-ZnO-NPs were found to have significant antiproliferative and anticancer activities on HGC-27 gastric cancer cells. Collectively, current data suggest that TP-ZnO-NP is a novel and promising anticancer agent for future therapeutic interventions in gastric cancer.

Salivary gland tumors exhibit distinct miRNA signatures involved in Wnt/ß-Catenin signaling in formalin fixed paraffin embedded tissue samples.

Advances in high-throughput genomic technologies have enabled the identification of numerous selective tumor markers. However, adapting these newly identified markers to clinical practice is not always possible because most RNA molecules, including mRNAs of protein-coding genes and long non-coding RNAs, are not stable under laboratory conditions, making their testing a major challenge. In contrast to long RNA molecules, miRNAs offer a great advantage in that they are relatively stable due to their small size. Accordingly, herein we aimed to determine the expression levels of miRNAs that are involved in Wnt/ß-catenin signaling pathway in formalin fixed paraffin embedded (FFPE) tissue samples of patients with salivary gland tumors. A total of 42 patients with salivary gland tumors were included in the study. The miRNA expression signatures were evaluated using the RT-qPCR. As a result, ß-catenin positivity was observed in all salivary gland tumors without distinguishing between benign and malignant phenotypes. Remarkably, we found that miR-200a and miR-373 were significantly upregulated whereas miR-30c were downregulated in tissues of patients with salivary gland tumors, compared to adjacent healthy tissue samples. In addition, distinct expression signatures of these miRNAs were significantly associated with the clinicopathological findings of patients such as perineural invasion and lymph node metastasis. Additionally, miR-145 and miR-30a were found to be specifically downregulated in a mucoepidermoid carcinoma. Also, miR-26b was selectively increased in pleomorphic adenomas of the salivary gland. Collectively, our findings suggest that these miRNAs may play chief roles in the differential diagnosis of salivary gland tumors.

miR-320a promotes p53-dependent apoptosis of prostate cancer cells by negatively regulating TP73-AS1 invitro.

TP73 antisense RNA 1 (TP73-AS1) is an oncogenic long non-coding RNA that is activated in several types of cancers. It has been shown that the activity of TP73-AS1 is controlled by several miRNAs, but post-transcriptional mechanisms that regulate TP73-AS1 activity in prostate cancer remain highly elusive. Accordingly, in the present study, we aimed to determine the miRNAs that are involved in the regulation of TP73-AS1 in prostate cancer and to show the effects of these molecules on the malignant proliferation of prostate cancer cells. Remarkably, colony formation and cell migration were suppressed while cell cycle arrest and apoptosis were induced in prostate cancer cells overexpressing miR-200a and miR-320a. miR-200a and miR-320a were found to be upregulated in TP73-AS1 suppressed prostate cancer cells. Also, TP73-AS1 was shown to be downregulated following miR-200a and miR-320a overexpression. However, overexpression of miR-320a had no significant effect on the expression of TP73. Further analysis revealed that miR-320a induces p53-dependent apoptosis. Consequently, our findings indicate that miR-320a induces p53-dependent apoptosis by negatively regulating TP73-AS1 long non-coding RNA.

Effects of Non-Thermal Treatment on Gilaburu Vinegar (Viburnum opulus L.): Polyphenols, Amino Acid, Antimicrobial, and Anticancer Properties.

Gilaburu (Viburnum opulus L.) is an important fruit that has been studied in recent years due to its phytochemicals and health benefits. In this study, traditionally produced vinegar made from gilaburu fruit (C-GV) was evaluated. Vinegar with higher levels of bioactive components optimized by response surface methodology (RSM) was also produced using ultrasound (UT-GV). The maximum optimization result for the bioactive components was achieved at 14 min and 61.2 amplitude. The effectiveness of thermal pasteurization (P-GV) on gilaburu vinegar was evaluated. An increase was detected for every organic acid with ultrasound treatment. In the UT-GV and C-GV samples, arabinose was present, which is useful for stimulating the immune system. Gilaburu vinegar samples contained 29-31 volatile compounds. The smallest amount of volatile compounds was found in P-GV (1280.9 µg/kg), and the largest amounts of volatile compounds were found in C-GV (1566.9 µg/kg) and UT-GV (1244.10 µg/kg). In the UT-GV sample, Fe was increased, but Ca, K, Mg, and Mn were decreased. A total of 15 polyphenols were detected in C-GV, P-GV, and UT-GV samples, and gallic acid was the most common. A total of 17 free amino acids were detected in gilaburu vinegar samples. Ultrasound provided enrichment in total phenolic compounds and total free amino acids. All three vinegar samples had good antimicrobial activity against pathogens. The efficacy of C-GV, P-GV, and UT-GV samples against colon and stomach cancer was determined, but there were no significant differences between them. As a result, ultrasound treatment is notable due to its antimicrobial and anticancer activity, especially for the enrichment of phenolic compounds and amino acids in gilaburu vinegar.

Deciphering miRNAs associated with cellular stress response and apoptosis mechanisms regulated by p53 activity in patients with lower lip cancer.

Cancers of the lips and oral cavity are a leading cause of death worldwide. Although they account for only 2% of the global cancer burden, they significantly affect the comfort of patients and eventually lead to a person's death. Also, defects in the cellular stress response and apoptosis mechanisms regulated by p53 activity is an important hallmark of cancer cells. Here, we aimed to decipher miRNAs associated with cellular stress response and apoptosis mechanisms regulated by p53 activity in patient with lower lip cancer and reveal the association of these miRNAs with the clinical course of the disease. The present research included a total of 40 eligible individuals with pathologically confirmed lower lip cancer diagnosis. Formalin-fixed, paraffin-embedded (FFPE) tissue samples of patients were obtained, and miRNAs expressions were analyzed by qPCR. Immunohistochemistry was used to determine p53 and Ki67 expression status. While three of these miRNAs (miR-130a, -375, and -128a) were found to be elevated in tumor cells compared to normal tissues of lower lip cancer patients, five were downregulated (let-7a, -7b, -7c, and miR-138, -23a), but only three were significantly altered. Particularly, we identified three miRNA signatures in which miR-128a was significantly upregulated and miR-23a and let-7c were significantly downregulated in patients with lower lip cancer. Remarkably, let-7c identified to be a promising prognostic factor for lip cancer. Our findings demonstrate that these miRNAs play important regulatory roles in lower lip cancer pathobiology, highlighting their potential relevance in diagnosis and prognosis of these patients. Moreover, these miRNAs can be targeted in future therapeutic interventions against lower lip cancer.

Distinct expression signatures of miR-130a, miR-301a, miR-454 in formalin fixed paraffin embedded tissue samples of prostate cancer patients.

Recent advances in high-throughput screening of human tumors have enabled the identification of numerous tumor markers. However, the clinical utility of these newly identified molecules remains enigmatic until they are well validated in patient samples. Although many long non-coding RNA molecules of clinical importance have been identified in the differential diagnosis of prostate cancer, the consistency of many of them in practice is still controversial. Therefore, short non-coding RNA molecules such as miRNAs are coming to the forefront in the differential diagnosis of the disease because of their stability. Accordingly, in the present study, we aimed to reveal the clinical significance of miR-130a, miR-301a, miR-454 expression levels in formalin fixed paraffin embedded (FFPE) tissue samples of prostate cancer patients. miRNA expression signatures were determined by RT-qPCR method. Notably, we found that miR-301a and miR-454 were significantly upregulated whereas miR-130a were downregulated in cancerous tissues of prostate cancer patients compared to adjacent healthy tissue samples. Moreover, differential expression of these miRNAs was significantly associated with patients' clinicopathological findings, such as Gleason score, lymphovascular invasion, perineural invasion, and extra-prostatic extension. Collectively, our observations indicate that these miRNAs may be of clinical importance in the differential diagnosis of prostate cancer.