Associations of Single Versus Multiple Human Papillomavirus Infections With the Prevalence of Cervical Intraepithelial Neoplasia 2/3 and Squamous Cell Carcinoma Lesions: Human Papillomavirus Type-Specific Attribution.

The risk of developing cervical squamous lesions in women with multiple high-risk human papillomavirus (hrHPV) infections is uncertain. The aim of this retrospective study was to investigate the type-specific attribution and phylogenetic effects of single and multiple hrHPV subtypes in cervical squamous lesions. All cases with cervical histopathologic diagnosis and human papillomavirus (HPV) genotyping results in the 6 months preceding biopsy from October 2018 to December 2022 were studied and analyzed. Over the study period, 70,361 cases with histopathologic follow-up and prior HPV genotyping were identified. The hrHPV-positive rate was 55.6% (39,104/70,361), including single hrHPV detected in 27,182 (38.6%), 2 types of hrHPV detected in 8158 (11.6%), and 3 types of hrHPV detected in 2486 (3.5%). Among 16,457 cases with a histologically diagnosed squamous lesion (cervical intraepithelial neoplasia 1: 11411; cervical intraepithelial neoplasia 2/3: 4192; squamous cell carcinoma: 854 cases), the prevalence of single hrHPV infection increased, but the rate of multiple concomitant hrHPV infections showed negative association as the degree of squamous lesions increased. Among women with a single HPV16 infection, cervical intraepithelial neoplasia 2/3 and squamous cell carcinoma (CIN2+) diagnostic rate was 30.6%, and it increased to 47.6% when coinfected with HPV33 (P < .001) but significantly decreased when coinfected with all other hrHPV types (P < .05). By comparing CIN2+ diagnostic rates in 40 most common 2 types of hrHPV infections with related single hrHPV infection, CIN2+ rates were decreased in 12 combinations (30.0%), equivalent in 26 combinations (65.0%), and increased in 2 combinations (5.0%). The cases with 3 types of HPV infections reduced the risk for CIN2+ compared with related single HPV infections. HPV16+52+53, HPV16+52+68, HPV16+52+51, HPV16+39+52, and HPV16+58+53 significantly decreased the risk of CIN2+ compared with HPV16 single infection (P < .05). This study demonstrates that multiple hrHPV infections are not associated with cumulatively higher risk for CIN2+ development, suggesting that oncogenic progression of multiple hrHPV-associated cervical squamous lesions is neither synergistic nor a cumulative effect at the phylogenetic level, possibly a way of competitive interference.

HPV genotyping of cervical histologic specimens of 61, 422 patients from the largest women hospital in China.

Objectives: We investigated HPV genotypes in a large cohort of patients with definitive cervical histologic diagnosis. Methods: HPV testing was performed by real-time PCR assay, including 18 high-risk HPV (hrHPV) and 3 low-risk HPV (lrHPV). Totally 61,422 patients with documented HPV genotyping results within 6 months before cervical histologic diagnoses were included. Results: HrHPV positive rate was 55.1% among all tested cases with the highest in adenosquamous carcinoma (94.1%), followed by squamous cell carcinoma (SCC) (93.7%), cervical intraepithelial neoplasia 2/3 (CIN2/3) (92.8%). HrHPV positive rates were significantly higher in high-grade squamous lesions than in those in glandular lesions. HPV16 was the most common genotype followed by HPV52 and HPV58 in CIN2/3. The most frequent hrHPV genotype in adenocarcinoma in situ (AIS) was HPV18, followed by HPV16, HPV45 and HPV52. In SCC cases, HPV16 was the most common type followed by HPV58, HPV52, HPV18 and HPV33. However, HPV18 showed significantly higher prevalence in adenocarcinoma and adenosquamous carcinoma than in that in SCC. Theoretically, the protective rates of 2/4-valent and 9-valent vaccine were 69.1% and 85.8% for cervical cancers. Conclusions: The prevalence of HPV genotypes in Chinese population was different from that in Western population. Some hrHPV types were identified in cervical precancerous lesions and cancers, which are not included in current HPV vaccines. These data provide baseline knowledge for future HPV vaccine development.

Human papillomavirus integration perspective in small cell cervical carcinoma.

Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, we report human papillomavirus features and genomic landscape in SCCC via high-throughput HPV captured sequencing, whole-genome sequencing, whole-transcriptome sequencing, and OncoScan microarrays. HPV18 infections and integrations are commonly detected. Besides MYC family genes (37.9%), we identify SOX (8.4%), NR4A (6.3%), ANKRD (7.4%), and CEA (3.2%) family genes as HPV-integrated hotspots. We construct the genomic local haplotype around HPV-integrated sites, and find tandem duplications and amplified HPV long control regions (LCR). We propose three prominent HPV integration patterns: duplicating oncogenes (MYCN, MYC, and NR4A2), forming fusions (FGFR3-TACC3 and ANKRD12-NDUFV2), and activating genes (MYC) via the cis-regulations of viral LCRs. Moreover, focal CNA amplification peaks harbor canonical cancer genes including the HPV-integrated hotspots within MYC family, SOX2, and others. Our findings may provide potential molecular criteria for the accurate diagnosis and efficacious therapies for this lethal disease.

Blood Coral Polysaccharide Helps Prevent D-Gal/LPS-Induced Acute Liver Failure in Mice.

Objective: The liver protection of blood coral polysaccharide (BCP) was investigated. Materials and Methods: We evaluated the effect of BCP on liver pathology, liver function, oxidation and inflammation-related indicators of D-Gal/LPS-induced acute liver failure (ALF) mice in vivo. Results: Liver index and liver pathology observation in mice showed that BCP could inhibit liver tissue swelling and hemorrhage, hepatocyte damage, and inflammatory infiltration in ALF. Serum liver function results showed that BCP effectively inhibits the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), total bilirubin (TBil), alkaline phosphatase (AKP), myeloperoxidase (MPO). High dose-blood coral polysaccharide (H-BCP) was better than silymarin. Serum antioxidant and immune results showed that BCP increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px), and inhibited the levels of malondialdehyde (MDA) and nitric oxide (NO). Also, BCP increased immunoglobulins G (IgG) and A (IgA) levels, thereby enhancing humoral immunity. Liver anti-inflammatory ELISA results showed that BCP reduced the levels of interleukin (IL)-6, IL-1ß, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, and enhanced the level of anti-inflammatory factor IL-10. H-BCP was the most effective treatment. Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) of liver tissues confirmed that BCP increases the relative expression levels of antioxidant and anti-inflammatory-related cuprozinc superoxide dismutase (Cu/Zn-SOD, SOD1), manganese superoxide dismutase (Mn-SOD, SOD2), CAT, GSH, GSH-Px, and IL-10. In contrast, it inhibits inflammation-related genes IL-6, IL-1ß, IL-17, TNF-α, IFN-γ, inducible nitric oxide synthase (iNOS, NOS2), and cyclooxygenase (COX)-2. In addition, BCP also inhibits the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and enhance B-cell inhibitor-α (IκB-α) gene relative expression in the liver, which may be related to NF-κB pathway inhibition. Conclusion: BCP prevents D-Gal/LPS-induced ALF in mice, and its effect is concentration dependent.

Effect of Lactobacillus fermentum HFY06 Combined with Arabinoxylan on Reducing Lipid Accumulation in Mice Fed with High-Fat Diet.

In this experiment, a high-fat diet was used to induce hyperlipidemia in mice to determine the synergistic effect of AX and L. fermentum HFY06 on the prevention of hyperlipidemia and its potential regulatory mechanism. The results of this study showed that after the AX and L. fermentum HFY06 synergistic intervention, the body weight, epididymal fat index, blood lipid level, and liver function indexes of mice were improved. In addition, the synbiotics comprising AX and L. fermentum HFY06 increased the CAT activity in the serum of mice on a high-fat diet, reduced NO and MDA levels, and improved the body's oxidative stress. From the perspective of molecular biology, on the one hand, AX and L. fermentum HFY06 synergistic intervention activated the AMPK pathway to regulate body lipid metabolism; up-regulated the mRNA expressions of CPT-1, PPAR-α, CYP7A1, and HSL; and down-regulated the mRNA expressions of ACC, C/EBPα, and LPL. On the other hand, the synergistic effect of AX and HFY06 enhanced the mRNA expressions of ZO-1, occludin, and claudin-1 in the small intestine of mice, increased the strength of the intestinal barrier, and optimized the composition of the intestinal microbiota. From the above results, it can be concluded that AX and L. fermentum HFY06 have a synergistic effect in improving hyperlipidemia. However, this study was only performed using animal models, and the lipid synthesis and metabolism mechanism are complicated; hence, further clinical studies are needed.

The clinical utility of extended high-risk HPV genotyping in risk-stratifying women with L-SIL cytology: A retrospective study of 8726 cases.

BACKGROUND: The value of extended high-risk human papillomavirus (hrHPV) genotyping for cervical cancer screening in women with low-grade squamous intraepithelial lesion (L-SIL) cytology has been recognized, but few studies have investigated this. METHODS: Women with L-SIL Papanicolaou results who underwent human papillomavirus (HPV) genotyping between October 2017 and October 2021 at the Obstetrics and Gynecology Hospital of Fudan University were identified. Their HPV results were correlated with immediate histopathologic follow-up findings. RESULTS: In total, 8726 women who had L-SIL cytology and extended HPV genotyping results were analyzed. The overall hrHPV-positive rate was 84% in women with L-SIL, and the most prevalent hrHPV genotypes were type 52 (HPV52) (20.7%), HPV53 (15.7%), and HPV16 (14.3%). Single and multiple coinfections of hrHPV genotypes were detected in 57.2% and 42.8% of women with positive hrHPV results, respectively. Cervical intraepithelial neoplasia grade ≥2 (CIN2+) was identified in 8.5% of hrHPV-positive women. The CIN2+ detection rate in women who had multiple hrHPV infections (9.9%) was significantly higher than the rate in those who had infection with a single HPV type (7.2%). The top 5 CIN2+-associated HPV infections were HPV16 (25.2%), HPV82 (17.8%), HPV33 (16.3%), HPV31 (14.6%), and HPV26 (13.8%). For the composite group with HPV types HPV16, HPV26, HPV82, HPV31, HPV18, HPV33, HPV58, HPV35, HPV52, and HPV51, the risk of CIN2+ was 11.5% and represented 97.1% of all CIN2+ in biopsied, hrHPV-positive patients. The composite group of 8 remaining HPV genotypes (HPV39, HPV45, HPV53, HPV56, HPV59, HPV66, HPV68, and HPV73) was identified in 29.7% of hrHPV-positive patients, and the risk of CIN2+ for this composite group was similar to the risk of CIN2+ in hrHPV-negative patients. CONCLUSIONS: This large retrospective study in a predominantly unvaccinated cohort demonstrated that extended hrHPV genotyping improves genotype-specific risk stratification in women with L-SIL.

Prophylactic Effect of Lactobacillus fermentum TKSN02 on Gastric Injury Induced by Hydrochloric Acid/Ethanol in Mice Through Its Antioxidant Capacity.

In this article, the preventive and protective effect of a new Lactobacillus fermentum, (Lactobacillus fermentum TKSN02: LF-N2), which was isolated and identified from Xinjiang naturally fermented yogurt, on hydrochloric acid (HCl)/ethanol induced gastric injury in mice was studied. A total of 40 mice were divided into the following five groups: normal, model, LF-N2, LB (Lactobacillus bulgaricus), and Ranitidine groups. Except for the normal and model groups, mice in the other groups were treated with LF-N2, LB (Lactobacillus bulgaricus), and Ranitidine separately, and the injury of the gastric tissue was observed by taking photos and pathological sections. The levels of oxidation indicators, gastrointestinal hormone and the inflammatory cytokines in serum and gastric tissue in each group were measured. Further more, the gene expression levels of oxidative stress and inflammation related genes in the colon tissue were determined by the Real-Time PCR method. Pathological observation confirmed that LF-N2 could inhibit the gastric injury caused by HCl/ethanol. Observation of the appearance of the gastric indicated that LF-N2 could effectively reduce the area of gastric injury. Biochemical results showed that the serum gastrin (GAS) and gastric motilin (MTL) levels in the LF-N2 group were significantly lower and the serum somatostatin (SS) level was higher than in the model group and there was no significant difference between all treatment groups. The activities of total superoxide dismutase (T-SOD) and glutathione (GSH) were increased while the malondialdehyde (MDA) content was decreased in LF-N2 treatment group mice, which suggested that LF-N2 has a good antioxidant effect. Further RT-PCR experiments also showed that LF-N2 could promote the related mRNA expression of antioxidant enzymes (Cu/Zn-SOD, Mn-SOD, and CAT) and anti-inflammatory cytokines (IL-4, and IL-10), while it inhibited the gene expression of pro-inflammatory cytokine (IL-6) and apoptosis factor (Caspase-3). As observed, LF-N2 exerted a good preventive effect on HCl/ethanol induced gastric injury in mice, and the effect was close to that of LB, which indicated that LF-N2 has potential use as a probiotic due to its gastric injury treatment effects.

[Prevalence and frequencies of human papilloma virus types in adenocarcinoma in situ of the uterine cervix].

Objective: To examine the prevalence and frequencies of human papillomavirus (HPV) genotypes in cervical adenocarcinoma in situ (AIS). Methods: The cases of cervical AIS with concurrent tests of cytology and HPV typing from January 2007 to February 2020 in the Obstetrics and Gynecology Hospital of Fudan University were collected and analyzed. Results: A total of 478 cases of cervical AIS were obtained. The average age of the patients was 39.4 years (range, 19-81 years). The largest age group was 30-39 years (44.8%), followed by 40-49 years (34.7%). Among the 478 patients, 355 underwent high-risk HPV (hrHPV) testing and had a hrHPV-positive rate of 93.8%. Of the 355 patients, 277 also underwent HPV typing and were mostly positive for either or both HPV16 and HPV18 (93.1%), with 55.6% positive for HPV18 and 48.7% positive for HPV16. Among the 478 cases, 266 cases (55.6%) were diagnosed with both AIS and squamous intraepithelial lesion (SIL), while 212 cases (44.4%) were diagnosed with only AIS. Patients infected with HPV16 in the AIS and SIL group significantly outnumbered those in the AIS alone group (P<0.05). Moreover, the rate of positive cytology was 55.9% (167/299 cases), while that of negative cytology was 44.1% (132/299). Among the 109 patients with negative cytology results and co-tested hrHPV, there were 101 HPV-positive cases (92.7%), of which 88 cases were subject to HPV typing and showed an HPV16/18 positive rate of 94.3% (83/88 cases). Conclusions: The combination of HPV typing and cytological screening can maximize the detection rate of cervical AIS, and should continue to be utilized, ideally on a larger scale, in the future.

Risk stratification for cervical neoplasia using extended high-risk HPV genotyping in women with ASC-US cytology: A large retrospective study from China.

BACKGROUND: Extended high-risk human papillomavirus (hrHPV) genotype testing (hrHPVGT) has emerged as a new strategy to help optimize the efficiency of hrHPV triage. METHODS: Women with an atypical squamous cells of undetermined significance (ASC-US) cervical Papanicolaou test result who underwent hrHPVGT between October 2017 and May 2021 at the Obstetrics and Gynecology Hospital of Fudan University in Shanghai, China, were studied. For hrHPVGT, a proprietary multiplex real-time polymerase chain reaction assay was used. hrHPVGT and viral load test results in selected patients were correlated with histopathologic follow-up findings available within 6 months. RESULTS: In total, 17,235 women with ASC-US cytology who had hrHPVGT results were identified in the Obstetrics and Gynecology Hospital of Fudan University database. The hrHPV-positive rate was 61.8%, and the most prevalent hrHPV genotypes were type 52 (HPV52) (16%), HPV16 (11.3%), HPV58 (10.2%), and HPV53 (8.4%). Single hrHPV genotypes were detected in 65.9% of women with hrHPV-positive results, and multiple genotypes were detected in 34.1%. Histopathologic cervical findings within 6 months were available in 5627 hrHPV-positive women and 2223 hrHPV-negative women. High-grade cervical intraepithelial lesions or cervical cancer (cervical intraepithelial neoplasia 2 or greater [CIN2+]) were identified in 7.5% of hrHPV-positive women who had ASC-US cytology and in 0.9% of hrHPV-negative women who had ASC-US cytology. The greatest risk for CIN2+ was in single hrHPV genotype infections with HPV16 (21.1%), HPV33 (15.2%), HPV82 (10%), and HPV18 (9.9%). hrHPVGT for genotypes HPV16, HPV33, HPV82, HPV18, HPV31, HPV45, HPV58, and HPV52 identified 95% of CIN2+ cases with 90.8% sensitivity, 53.8% specificity, a positive predictive value of 10.2%, and a negative predictive value of 99%. A significantly increased viral load was associated only with women who had HPV16-related CIN2+. CONCLUSIONS: hrHPVGT for women who have ASC-US cytology allows for risk stratification capable of optimizing the efficiency of triage for hrHPV-positive women.

A Mixture of Lactobacillus fermentum HFY06 and Arabinoxylan Ameliorates Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis in Mice.

OBJECTIVE: Colitis is one of the main gastrointestinal diseases threatening human health. MATERIALS AND METHODS: In this study, a synbiotic composed of arabinoxylan (AX) and Lactobacillus fermentum HFY06 was tested to determine its ability to relieve dextran sulfate sodium (DSS)-induced colitis. RESULTS: The experimental results showed that the synergistic effect of AX and L. fermentum HFY06 alleviated the weight loss of DSS-mediated colitis mice and lowered the disease activity index (DAI) score. Determination of biochemical indicators found that the synbiotic composed of AX and L. fermentum HFY06 increased the body's antioxidant capacity and reduced inflammation. The histopathological examination results showed that the colonic crypts of the mice in the model group were disordered, goblet cells were lost, and the mucous membrane was severely damaged. However, the combination of AX and L. fermentum HFY06 can significantly reverse the histopathological changes in the colon mediated by DSS. The gene expression of colon tissue was further determined, and the results showed that the synergistic effect of AX and L. fermentum HFY06 inhibited the activation of the NF-κB signaling pathway, downregulated the mRNA expression levels of nuclear factor-κB-p65 (NF-κBp65), upregulated the mRNA expression of NF-κB inhibitor-α (IκB-α), inhibited the release of cytokines tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2), and exerted anti-colitis effects. CONCLUSION: This study shows that the synbiotic composed of AX and L. fermentum HFY06 has the potential to prevent and treat colitis.

Plant protein reduces serum cholesterol levels in hypercholesterolemia hamsters by modulating the compositions of gut microbiota and metabolites.

Plant proteins exert effects of reducing cardio-cerebrovascular disease-related mortality partly via cholesterol-lowering, which was associated with gut microbiota. Here, we verify that there are significant differences in cholesterol levels among hamsters consuming different proteins. The decisive roles of gut microbiota in regulating host cholesterol are illustrated by the fact that the difference in serum cholesterol levels between hamsters feeding with pea protein and pork protein disappeared when treated with antibiotics. The results of cross-over intervention of pea and pork protein show that serum cholesterol levels are reversed with dietary exchange. The corresponding changes in microbiota suggest that Muribaculaceae are responsible for the inhibitory effect of pea protein on serum cholesterol level, whereas the opposite effect of pork protein is due to Erysipelotrichaceae. Moreover, pea protein supplement alters cecal metabolites including arginine/histidine pathway, primary bile acid biosynthesis, short-chain fatty acids, and other lipid-like molecules involved in cholesterol metabolism.

Effects of Xylooligosaccharides on Lipid Metabolism, Inflammation, and Gut Microbiota in C57BL/6J Mice Fed a High-Fat Diet.

Xylooligosaccharide (XOS) is a source of prebiotics with multiple biological activities. The present study aimed to investigate the effects of XOS on mice fed a high-fat diet. Mice were fed either a normal diet or a high-fat diet supplemented without or with XOS (250 and 500 mg/kg), respectively, for 12 weeks. The results showed that the XOS inhibited mouse weight gain, decreased the epididymal adipose index, and improved the blood lipid levels, including triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels. Moreover, XOS reduced the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and alleviated the damage to the liver caused by the high-fat diet. XOS also reduced hyperlipidemia-associated inflammatory responses. Additionally, quantitative real-time polymerase chain reaction results showed that XOS intervention activated the AMP-activated protein kinase (AMPK) pathway to regulate the fat synthesis, decomposition, and ß oxidation; upregulated the mRNA expression levels of carnitine palmitoyl transferase 1 (CPT-1), peroxisome proliferator-activated receptors α (PPAR-α), and cholesterol 7-alpha hydroxylase (CYP7A1); and downregulated the mRNA expression levels of acetyl-CoA carboxylase (ACC), CCAAT/enhancer-binding protein alpha (C/EBPα), and lipoprotein lipase (LPL). On the other hand, XOS enhanced the mRNA expression levels of zonula occludens-1 (ZO-1), occludin, and claudin-1 in the small intestine; increased the strength of the intestinal barrier; and optimized the composition of the intestinal microbiota. Therefore, it was concluded that XOS regulated the intestinal barrier, changed the intestinal microecology, and played an important role in preventing hyperlipidemia through the unique anatomical advantages of the gut-liver axis.

Pathogenicity of the MAGE family.

The melanoma antigen gene (MAGE) protein family is a group of highly conserved proteins that share a common homology domain. Under normal circumstances, numerous MAGE proteins are only expressed in reproduction-related tissues; however, abnormal expression levels are observed in a variety of tumor tissues. The MAGE family consists of type I and II proteins, several of which are cancer-testis antigens that are highly expressed in cancer and serve a critical role in tumorigenesis. Therefore, this review will use the relationship between MAGEs and tumors as a starting point, focusing on the latest developments regarding the function of MAGEs as oncogenes, and preliminarily reveal their possible mechanisms.

Lactobacillus fermentum HFY06 attenuates D-galactose-induced oxidative stress and inflammation in male Kunming mice.

There has been considerable research on oxidative stress and inflammation, and their relationship with degenerative diseases. This study investigated the effect of Lactobacillus fermentum HFY06 on aging mice induced by D-galactose. The results showed that L. fermentum HFY06 inhibited the atrophy of the brain, kidneys, liver, and spleen, increased serum SOD, GSH, CAT, and MDA, and decreased IL-6, IL-1ß, TNF-α, and IFN-γ. Quantitative PCR showed that L. fermentum HFY06 upregulated the expression of Nrf2, γ-GCS, NOS1, NOS3, SOD1, SOD2, and CAT in the liver and brain tissues, but decreased the expression of NOS2. Western blot analysis showed that L. fermentum HFY06 effectively upregulated the protein expression of SOD1, SOD2, and CAT in the livers and brains of mice. These results suggest that L. fermentum HFY06 can effectively alleviate D-galactose-induced aging in mice, and may activate the Nrf2 signaling pathway and increase the levels of downstream regulatory inflammatory factors and antioxidant enzymes. In conclusion, consumption of L. fermentum HFY06 may prevent aging or reduce oxidative stress.

MicroRNA-mediated bioengineering for climate-resilience in crops.

Global projections on the climate change and the dynamic environmental perturbations indicate severe impacts on food security in general, and crop yield, vigor and the quality of produce in particular. Sessile plants respond to environmental challenges such as salt, drought, temperature, heavy metals at transcriptional and/or post-transcriptional levels through the stress-regulated network of pathways including transcription factors, proteins and the small non-coding endogenous RNAs. Amongs these, the miRNAs have gained unprecedented attention in recent years as key regulators for modulating gene expression in plants under stress. Hence, tailoring of miRNAs and their target pathways presents a promising strategy for developing multiple stress-tolerant crops. Plant stress tolerance has been successfully achieved through the over expression of microRNAs such as Os-miR408, Hv-miR82 for drought tolerance; OsmiR535A and artificial DST miRNA for salinity tolerance; and OsmiR535 and miR156 for combined drought and salt stress. Examples of miR408 overexpression also showed improved efficiency of irradiation utilization and carbon dioxide fixation in crop plants. Through this review, we present the current understanding about plant miRNAs, their roles in plant growth and stress-responses, the modern toolbox for identification, characterization and validation of miRNAs and their target genes including in silico tools, machine learning and artificial intelligence. Various approaches for up-regulation or knock-out of miRNAs have been discussed. The main emphasis has been given to the exploration of miRNAs for development of bioengineered climate-smart crops that can withstand changing climates and stressful environments, including combination of stresses, with very less or no yield penalties.

ß-Nicotinamide Mononucleotide (NMN) Administrated by Intraperitoneal Injection Mediates Protection Against UVB-Induced Skin Damage in Mice.

OBJECTIVE: Ultraviolet light is an important environmental factor that induces skin oxidation, inflammation, and other diseases. Nicotinamide mononucleotide (NMN) has the effect of anti-oxidation and improving various physiological processes. This study explores the protective effect of NMN monomers given via intraperitoneal injection on UVB-induced photodamage. METHODS: We used a murine model of UVB-induced photodamage to evaluate the effect of an NMN monomer on photoaging skin by assessing skin and liver tissue sections, serum and skin oxidative stress levels, inflammatory markers, mRNA expression, and protein expression of skin- and liver-related genes. RESULTS: The results showed that NMN treatment blocked UVB-induced photodamage in mice, maintaining normal structure and amount of collagen fibers, normal thickness of epidermis and dermis, reducing the production of mast cells, and maintaining complete organized skin structure. NMN intraperitoneal injection also maintained the normal morphology of the mouse liver after UVB exposure. Meanwhile, NMN intraperitoneal injection was found to increase antioxidant ability and regulate the proinflammatory response of the skin and liver to UVB irradiation by enhancing the activity of antioxidant enzymes, release of anti-inflammatory cytokines, reduction of hydrogen peroxide production (H2O2), and decreased inflammatory cytokines. Furthermore, RT-qPCR results indicated that NMN reduced oxidative stress of skin and liver by promoting the activation of the AMP-activated protein kinase (AMPK) signaling pathway and further increasing the expression of downstream antioxidant genes of AMPK. RT-qPCR results also revealed that NMN treatment could downregulate the mRNA expression of interleukin (IL)-6, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α, and upregulate NF-kappa-B inhibitor-α (IκB-α) and interleukin (IL)-10 by inhibiting the activation of nuclear factor-κBp65 (NFκB-p65). Finally, NMN upregulated AMPK, IκB-α, SOD1, and CAT in the skin and downregulated NF-κBp65 protein expression, which is in line with the RT-qPCR results. CONCLUSION: Based on the above results, NMN monomer treatment with intraperitoneal injection also block the photodamage caused by UVB irradiation in mice by regulating the oxidative stress response and inflammatory response.

Antioxidant Effect of Lactobacillus fermentum CQPC04-Fermented Soy Milk on D-Galactose-Induced Oxidative Aging Mice.

The aim of this study is to evaluate the changes in soy isoflavones and peptides in soy milk after lactic acid bacterial fermentation, and explore the positive effects of fermented soy milk on an oxidative aging mouse model induced with D-galactose. We found that free soybean isoflavones and peptides increased after soy milk was fermented by Lactobacillus fermentum CQPC04. The in vivo results indicated that L. fermentum CQPC04-fermented soy milk enhanced the organ index of the liver and spleen, and improved the pathological morphology of the liver, spleen, and skin. L. fermentum CQPC04-fermented soy milk increased the enzymatic activity of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), and catalase (CAT), increased glutathione (GSH), but decreased the levels of nitric oxide (NO) and malondialdehyde (MDA) in serum, liver, and brain tissues of oxidative aging mice. The above mentioned fermented soy milk also increased the levels of collagen I (Col I), hyaluronic acid (HA), and collagen III (Col III), and decreased the levels of advanced glycation End products (AGEs) and hydrogen peroxide (H2O2). The RT-qPCR results showed that L. fermentum CQPC04-fermented soy milk upregulated the mRNA expression of nuclear factor erythroid 2?related factor (Nrf2), heme oxygenase-1 (HMOX1), quinone oxido-reductase 1 (Nqo1), neuronal nitric oxide synthase (NOS1), endothelial nitric oxide synthase (NOS3), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-superoxide dismutase (Mn-SOD), and CAT, but downregulated the expression of inducible nitric oxide synthase (NOS2) and glutamate cysteine ligase modifier subunit (Gclm) in liver and spleen tissues. Lastly, the fermented soy milk also increased the gene expression of Cu/Zn-SOD, Mn-SOD, CAT, GSH-Px, matrix metalloproteinases 1 (TIMP1), and matrix metalloproteinases 2 (TIMP2), and decreased the expression of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in skin tissue. In conclusion, L. fermentum CQPC04-fermented soy milk was able to satisfactorily delay oxidative aging effects, and its mechanism may be related to the increase in free soy isoflavones and peptides.

Effect of Lactobacillus fermentum TKSN041 on improving streptozotocin-induced type 2 diabetes in rats.

With the increasing incidence of type 2 diabetes, it is imperative to identify how to effectively prevent or treat this disease. Studies have shown that some lactic acid bacteria can improve type 2 diabetes with almost no side effects. Therefore, in this experimental study, we explored the preventive and therapeutic effects of Lactobacillus fermentum TKSN041 (L. fermentum TKSN041) on streptozotocin-induced type 2 diabetes in rats. The results showed that L. fermentum TKSN041 could reduce the amount of water intake, reduce weight loss, and control the increase in the fasting blood glucose level of diabetic rats. The organ index and tissue section results showed that L. fermentum TKSN041 could reduce the damage caused by diabetes to the liver, kidney, spleen, pancreatic, and brain tissue. Furthermore, L. fermentum TKSN041 decreased the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), aminotransferase (AST), alanine aminotransferase (ALT), glycated serum proteins (GSP), malondialdehyde (MDA), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and endothelin 1 (ET-1) in serum and increased the serum levels of high-density lipoprotein cholesterol (HDL) and interleukin 10 (IL-10). Finally, L. fermentum TKSN041 up-regulated the mRNA and protein expressions of NF-kappa-B inhibitor-α (IκB-α), AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), liver kinase B1 (LKB1), and glucose transporter 4 (GLUT4) and down-regulated those of nuclear factor-κBp65 (NFκB-p65) and tumor necrosis factor alpha (TNF-α). Furthermore, LF-TKSN041 up-regulated the mRNA expressions of peroxisome proliferator-activated receptor γ (PPAR-γ) and down-regulated neuropeptide Y (NPY), sterol regulatory element-binding protein-1 (SREBF-1), and vascular endothelial growth factor (VEGF). These results suggest that L. fermentum TKSN041 may be a useful intervention factor for the prevention or treatment of type 2 diabetes induced by STZ. Clinical trials are needed to further demonstrate its effectiveness.

Quality improvement effects of electrolyzed water on rice noodles prepared with semidry-milled rice flours.

To investigate the effects of electrolyzed water treatment on the qualities of rice noodles prepared with semidry- milled rice flour, pasting properties and thermal properties of rice flour, and the cooking and textural properties of rice noodles were determined. Higher peak viscosity and lower melting enthalpy were observed in electrolyzed water (EW) treated rice flour. The hardness, gumminess and chewiness of rice noodle in slightly acidic electrolyzed water treated rice noodles with available chlorine concentration (ACC) 20.32 mg/L were increased significantly (p < 0.05). The cooking loss decreased significantly in strong acidic electrolyzed water treated noodles with ACC 10.09 mg/L treatment (p < 0.05). The results indicated that EW could promote the gelatinization of rice flour, and improve the textural qualities of rice noodles. Therefore EW was appropriate to be used in rice noodle production.