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.

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.

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.

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.

Hepatoprotective Effect of Lactobacillus plantarum HFY09 on Ethanol-Induced Liver Injury in Mice.

Lactobacillus plantarum is a bacterial strain that is used as a probiotic with health-promoting effects. Our study investigated the hepatoprotective effect of Lactobacillus plantarum HFY09 (LP-HFY09) in mice with ethanol-induced liver injury. The protection afforded by LP-HFY09 was evaluated by observing the morphology of hepatic tissue and measuring liver lipid indexes and function indexes, levels of anti-oxidative enzymes, and anti-inebriation enzymes, as well as oxidative metabolism-related gene expression. Gavage administration of LP-HFY09 [1 × 109 CFU/kg body weight (bw)] limited the loss of bw, alcohol damage to the liver, and maintained the normal hepatic tissue morphology. Lactobacillus plantarum HFY09 intervention in ethanol-induced mice led to decreases in serum triglyceride (TG), total cholesterol (TC), aspartic transaminase, alanine transaminase, hyaluronidase (HAase), and precollagen III (PC III), and increases in liver alcohol dehydrogenase (ADH), and acetaldehyde dehydrogenase (ALDH). Lactobacillus plantarum HFY09 assisted with alleviating inflammation by elevating the level of interleukin 10 (IL-10) and decreasing the levels of pro-inflammatory factors [IL-6, IL-1ß, and tumor necrosis factor-α (TNF)-α]. Lactobacillus plantarum HFY09 significantly elevated hepatic levels of superoxide dismutase (SOD) and glutathione (GSH), and decreased liver malondialdehyde (MDA) from 3.45 to 1.64 nmol/mg protein. Lactobacillus plantarum HFY09 exhibited an overall strong regulatory effect on liver protection when compared to that of commercial Lactobacillus delbrueckii subsp. bulgaricus. The hepatoprotective effect of LP-HFY09 was reflected by the upregulated expression of peroxisome proliferator activated-receptors α, SOD1, SOD2, glutathione peroxidase (GSH-Px), nicotinamide adenine dinucleotide phosphate (NADPH), and catalase (CAT), and the downregulated expression of cyclooxygenase-1 (COX1), c-Jun N-terminal kinase (JNK), and extracellular regulated protein kinases (ERK). Administration of LP-HFY09 at a concentration of 1.0 × 109 CFU/kg bw could be a potential intervention, for people who frequently consume alcohol.

Antioxidant Effect of Soymilk Fermented by Lactobacillus plantarum HFY01 on D-Galactose-Induced Premature Aging Mouse Model.

The antioxidant effect of soymilk fermented by Lactobacillus plantarum HFY01 (screened from yak yogurt) was investigated on mice with premature aging induced by D-galactose. In vitro antioxidant results showed that L. plantarum HFY01-fermented soymilk (LP-HFY01-DR) had better ability to scavenge the free radicals 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) diammonium salt (ABTS) than unfermented soymilk and Lactobacillus bulgaricus-fermented soymilk. Histopathological observation showed that LP-HFY01-DR could protect the skin, spleen and liver, reduce oxidative damage and inflammation. Biochemical results showed that LP-HFY01-DR could effectively upregulate glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels and decrease malondialdehyde (MDA) content in the liver, brain, and serum. Real-time quantitative reverse transcription polymerase chain reaction further showed that LP-HFY01-DR could promote the relative expression levels of the genes encoding for cuprozinc superoxide dismutase (Cu/Zn-SOD, SOD1), manganese superoxide dismutase (Mn-SOD, SOD2), CAT, GSH, and GSH-Px in the liver, spleen, and skin. High-performance liquid chromatography results revealed daidzin, glycitin, genistin, daidzein, glycitein, and genistein in LP-HFY01-DR. In conclusion, LP-HFY01-DR could improve the antioxidant capacity in mice with premature aging induced by D-galactose.

Prevalence and carcinogenic risk of high-risk human papillomavirus subtypes in different cervical cytology: a study of 124,251 cases from the largest academic center in China.

INTRODUCTION: We investigated the prevalence and carcinogenic risks of individual high-risk human papillomavirus (HR-HPV) in all types of cervical cytology specimens in the Shanghai population. METHODS: A total of 124,251 cases with cotesting of cytology and HPV genotyping between October 2017 and February 2020 were included. RESULTS: The overall HPV positive rate was 24.3%, with 22.9% for HR-HPV and 6.1% for low-risk HPV. The top five most common HR-HPV subtypes were HPV 52/16/58/53/39 in the entire studied population, and HPV 16/53/56/51/39 in women with abnormal cytology. The most prevalent subtypes in negative/LSIL, HSIL, and glandular lesions were HPV 52, 16, and 18, respectively. HPV 16, 33, 26, 18, 58, and 82 were the most common subtypes significantly associated with an increased risk for HSIL + cytology. HPV 16/18 were present in 53.6% and 66.7%, and HPV 16/18/31/33/45/52/58 were identified in 90.3% and 80.1% of HSIL and squamous cell carcinoma cytology, respectively. HPV 16/18 and HPV 16/18/31/33/45/52/58 were detected in 37.0% and 44.4% of women with cytologic interpretation of in situ and invasive adenocarcinoma. CONCLUSIONS: This large-scale study identified the most common HPV subtypes in each cytology category, and the carcinogenic risks of individual HR-HPV in the studied Shanghai population. The results would provide valuable information for the development of next-generation HPV vaccines and cervical cancer screening programs for the Chinese population, and, more specifically, the Shanghai metropolitan population.

Nicotinamide Mononucleotide Combined With Lactobacillus fermentum TKSN041 Reduces the Photoaging Damage in Murine Skin by Activating AMPK Signaling Pathway.

Long-term exposure to UVB (280-320 nm) can cause oxidative skin damage, inflammatory injury, and skin cancer. Research on nicotinamide mononucleotide (NMN) and lactic acid bacteria (LAB) with regard to antioxidation, anti-inflammation, and prevention of other age-related diseases has received increasing attention. In the present study, the in vitro antioxidant analysis showed that NMN combined with Lactobacillus fermentum TKSN041 (L. fermentum TKSN041) has a high scavenging ability on hydroxyl (OH), 2, 2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) diammonium salt (ABTS) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH), and it also possess a good total antioxidant capacity. The animal experimental results show that NMN combined with LAB maintained normal liver morphology of mice and reduced pathological damage to murine skin. NMN combined with LAB significantly increased the serum levels of total superoxide dismutase (T-SOD), catalase (CAT), and interleukin (IL)-10, but reduced the levels of malondialdehyde, advanced glycation end products, tumor necrosis factor (TNF)-α, and IL-6. NMN combined with LAB increased T-SOD, CAT, IL-10, Na+-K+-ATPase, and NAD+ levels in the skin, but reduced TNF-α level in the skin. NMN combined with LAB increased the mRNA expression levels of SOD1, CAT, glutathione (GSH), inhibitor of NF-κB (IκB-α), IL-10, AMP-activated protein kinase (AMPK), adaptor protein, phosphotyros ineinteraction, PH domain and leucine zipper containing 1 (APPL1), peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α), and forkhead transcription factor O (FOXO) in the skin and liver, but decreased the mRNA expression levels of nuclear factor (NF)-κBp65, TNF-α, IL-6, and rapamycin target protein (mTOR). NMN combined with LAB increased the protein expression levels of AMPK, IκB-α, SOD1, and CAT in the skin tissues and reduced protein expression of NF-κBp65. NMN combined with L. fermentum TKSN041 improved murine skin damage caused by UVB irradiation, and the protective mechanism may be related to activation of the AMPK signaling pathway. The results of this study are expected to provide a reference for preventing and the treating skin photoaging.

Lactobacillus fermentum CQPC07 attenuates obesity, inflammation and dyslipidemia by modulating the antioxidant capacity and lipid metabolism in high-fat diet induced obese mice.

BACKGROUND: Obesity is an epidemic disease in the world, the treatment and prevention of obesity methods have gained great attention. Lactobacillus is the main member of probiotics, and the physiological activity of it is specific to different strains. This study systematically explored the anti-obesity effect and possible mechanism of Lactobacillus fermentum CQPC07 (LF-CQPC07), which was isolated from pickled vegetables. RESULTS: LF-CQPC07 effectively controlled the weight gain of mice caused by a high-fat diet. The results of pathological sections indicated that LF-CQPC07 alleviated hepatocyte damage and fat accumulation in adipocytes. The detection of biochemical indictors revealed that LF-CQPC07 decreased the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), and increased the level of high-density lipoprotein cholesterol (HDL-C). Additionally, LF-CQPC07 caused the decrease in the amounts of inflammatory cytokines interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), IL-6, and interferon-γ (IFN-γ), and the increase in the amounts of the anti-inflammatory cytokines IL-10 and IL-4. LF-CQPC07 also decreased the amounts of alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). Confirmed by qPCR, LF-CQPC07 enhanced the mRNA expression of catalase (CAT), gamma glutamylcysteine synthetase 1 (GSH1), copper/zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), and glutathione peroxidase (GSH-Px). It also increased the mRNA expression levels of carnitine palmitoyltransferase 1 (CPT1), peroxisome proliferator-activated receptor alpha (PPAR-α), lipoprotein lipase (LPL), and cholesterol 7 alpha hydroxylase (CYP7A1), and decreased that of PPAR-γ and CCAAT/enhancer binding protein alpha (C/EBP-α) in the liver of mice. CONCLUSION: This research confirmed that LF-CQPC07 is capable of ameliorating obesity, improving hyperlipemia, and alleviating chronic low-grade inflammation and liver injury accompanied with obesity. Its mechanism may be the regulation of antioxidant capacity and lipid metabolism. Therefore, LF-CQPC07 has enormous potential to serve as a potential probiotic for the prevention or treatment of obesity.

Lactobacillus fermentum ZS09 Mediates Epithelial-Mesenchymal Transition (EMT) by Regulating the Transcriptional Activity of the Wnt/ß-Catenin Signalling Pathway to Inhibit Colon Cancer Activity.

OBJECTIVE: The epithelial-mesenchymal transition (EMT) pathway can mediate tumour migration, and the occurrence of EMT is closely related to the Wnt/ß-catenin signalling pathway. The purpose of this paper was to study the effect of Lactobacillus fermentum ZS09 (L. fermentum ZS09) on the EMT pathway in mouse with azoxymethane/dextran sulfate sodium salt (AOM/DSS) induced colon cancer and the potential underlying mechanism. MATERIALS AND METHODS: In this study, a mouse colon cancer model was established through intraperitoneal injection of 10 mg/kg azoxymethane (AOM) and three cycles of 2.5% dextran sulfate sodium salt (DSS) in the drinking water. H&E staining, enzyme-linked immunosorbent assay (ELISA), real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting (WB) were used to study the antitumour mechanisms of L. fermentum ZS09 through the EMT pathway. RESULTS: The results of this study showed that compared with the model group, the high-dose L. fermentum ZS09 intervention group exhibited decreased serum levels of MMP-9, TNF-α, IL-6R, Ang-2 and VEGFR-2 and increased contents of DKK1 (P<0.05). The expression of Wnt/ß-catenin signalling pathway-related genes (Dv1, GSK-3ß, ß-catenin, c-myc, cyclinD1, Vim, and MMP-9) was significantly reduced, and the gene expression levels of APC, CDH1, and Axin were increased. The levels of related proteins (ß-catenin, N-cadherin, and VEGF) were downregulated, and the levels of p-ß-catenin and E-cadherin were upregulated. CONCLUSION: The results indicate that L. fermentum ZS09 could inhibit EMT and angiogenesis pathways by inhibiting the Wnt/ß-catenin signalling pathway, which could inhibit tumour metastasis.

Atypical squamous cells of undetermined significance cervical cytology in the Chinese population: Age-stratified reporting rates, high-risk HPV testing, and immediate histologic correlation results.

BACKGROUND: The US American Society of Colposcopy and Cervical Pathology guidelines for cervical cancer screening have been largely adopted worldwide. Pooled high-risk human papillomavirus (hrHPV) testing has been routinely used to risk-stratify women who have atypical squamous cells of undetermined significance (ASC-US) cytology. However, it has been reported that there are distinguished differences in the distribution of hrHPV genotypes between the Chinese and American populations. METHODS: The objective of this study was to analyze the age-stratified reporting rates, hrHPV-positive rates, and genotyping by different cytology preparation methods and hrHPV testing assays, along with the immediate histopathologic correlation of ASC-US cytology, in the Chinese population. RESULTS: The ASC-US reporting rate of 1,597,136 Papanicolaou (Pap) tests was 4.2%, and the overall hrHPV-positive rate was 48.7% in the ASC-US cases. In total, 25,338 women with ASC-US Pap tests had immediate histologic follow-up, and the detection rate for cervical intraepithelial neoplasia 2 and higher lesions (CIN2+) was 7.1%, including 0.6% carcinomas. Among the women who underwent hrHPV testing, CIN2+ lesions were identified in 657 of 6154 (10.7%) who had hrHPV-positive results and in only 1.5% those who had hrHPV-negative results. Further genotyping analysis revealed that HPV types 16 and/or 18 were commonly identified genotypes among the Chinese women who had ASC-US cytology. CONCLUSIONS: This large-scale study demonstrated that the hrHPV-positive rate, the CIN2+ detection rate, and the distribution of hrHPV genotypes in Chinese women with ASC-US cytology were essentially consistent with those from the American population, further supporting that the current and newly released 2019 American Society of Colposcopy and Cervical Pathology guidelines should be applicable to the Chinese population.