What factors may affect the effect of ICI-combined therapy in patients with metastatic renal cell carcinoma? A meta-analysis.

OBJECTIVE: The prognostic factors of ICI-including combined therapy in patients with metastatic renal cell carcinoma were analyzed by systematic review. METHOD: We searched Web of Science, Cochrane, PubMed, CNKI, Wanfang and other databases for randomized controlled trials and clinical trials of combination therapy including ICIs in the treatment of metastatic renal cell carcinoma. The search time was from the establishment of the database to September 2023. Data were extracted and evaluated with RevMan 5.4 software. RESULTS: Six studies were included, including 4723 patients. The results showed that ① in terms of progression-free survival, the factors of age < 65 years old, male sex, Canada and Western Europe, nephrectomy, different IMDC class, number of organs with metastases and PD-L1 expression ≥ 1% significantly prolonged PFS in patients with metastatic cancer treated by combination therapy including ICIs; ② in terms of overall survival rate, the factors of age < 65 years old, female sex, nephrectomy, different IMDC class and PD-L1 expression ≥ 1% significantly prolonged the OS of patients with metastatic cancer treated by combination therapy including ICIs. CONCLUSIONS: Age, sex, region, nephrectomy, different IMDC class, number of organs with metastases and PD-L1 expression are independent factors influencing the efficacy of combination therapy including ICIs in the treatment of metastatic renal cell carcinoma. Systematic evaluation of baseline indicators of patients with metastatic renal cell carcinoma to predict clinical benefits can effectively improve the benefit rate of patients.

Marine Bioactive Peptides: Anti-Photoaging Mechanisms and Potential Skin Protective Effects.

Skin photoaging, resulting from prolonged exposure to ultraviolet radiation, is a form of exogenous aging that not only impacts the aesthetic aspect of the skin but also exhibits a strong correlation with the onset of skin cancer. Nonetheless, the safety profile of non-natural anti-photoaging medications and the underlying physiological alterations during the process of photoaging remain inadequately elucidated. Consequently, there exists a pressing necessity to devise more secure interventions involving anti-photoaging drugs. Multiple studies have demonstrated the noteworthy significance of marine biomolecules in addressing safety concerns related to anti-photoaging and safeguarding the skin. Notably, bioactive peptides have gained considerable attention in anti-photoaging research due to their capacity to mitigate the physiological alterations associated with photoaging, including oxidative stress; inflammatory response; the abnormal expression of matrix metalloproteinase, hyaluronidase, and elastase; and excessive melanin synthesis. This review provides a systematic description of the research progress on the anti-photoaging and skin protection mechanism of marine bioactive peptides. The focus is on the utilization of marine bioactive peptides as anti-photoaging agents, aiming to offer theoretical references for the development of novel anti-photoaging drugs and methodologies. Additionally, the future prospects of anti-aging drugs are discussed, providing an initial reference for further research in this field.

Allicin Alleviates Mitochondrial Dysfunction in Acrylamide-Induced Rat Kidney Involving the Regulation of SIRT1.

Acrylamide (AA), commonly formed in carbohydrate-rich thermally processed foods, exerts harmful effects on the kidney. Allicin, from crushed garlic cloves, exhibits strong biological activities. In the current study, the protection mechanisms of allicin against AA-caused nephrotoxicity were comprehensively examined using an in vivo rat model based on previous research that allicin plays a key role in improving renal function. The results showed that allicin attenuated histological changes of the kidney and ameliorated renal function. Damaged mitochondrial structures, upregulated voltage-dependent anion channel 1 expression, and decreased membrane potential and adenosine 5'-triphosphate levels were observed after AA treatment. Surprisingly, allicin notably reversed the adverse effects. Further, allicin effectively restored mitochondrial function via modulating mitochondrial biogenesis and dynamics, which might be associated with the upregulated expression of sirtuin 1 (SIRT1). Meanwhile, allicin dramatically activated the SIRT1 activity and subsequently inhibited p53 acetylation, prevented the translocation of cytochrome c to the cytoplasm, and reduced the caspase expression, thus further inhibiting mitochondrial apoptosis caused by AA. In summary, the relieving effect of allicin on AA-caused nephrotoxicity lies in its inhibition of mitochondrial dysfunction and mitochondrial apoptosis.

A diagnostic test of real-time PCR detection in the diagnosis of clinical bloodstream infection.

BACKGROUND: Blood culture remains the standard for diagnosing bloodstream infections, but it is difficult to identify bacteria directly and timeliness. The real-time polymerase chain reaction (PCR) has the potential to fill this diagnostic gap. This study intends to explore the sensitivity and specificity of PCR in detecting bloodstream infection pathogens and to compare it with routine blood culture to explore its clinical application value. METHODS: A total of 126 patients with bloodstream infections collected from various clinical departments of The First Hospital of Hebei Medical University. The patient's sample was divided into two parts. The one for multiplex PCR detection was performed using the Pathogeno Elite Multiplex PCR kit. Another blood culture was a fully automatic blood culture system from Autobio company. RESULTS: Among the 126 patients, a total of 17 pathogens were detected by PCR and blood culture both methods. PCR detected a total of 43 positive samples and 83 negative samples. Five samples were positive with blood culture, and 81 were negative. The negative predictive value of PCR was 0.98, with a sensitivity of 0.71 and a specificity of 0.68. A total of 38 specimens were positive for PCR but negative for blood culture, and 2 samples were positive for blood culture but negative for PCR. The top 5 pathogens with PCR detection were Epstein-Barr virus (27 cases), Human herpes virus 5 (9 cases), Klebsiella pneumoniae (5 cases), Staphylococcus (5 cases), and Stenotrophomonas maltophilia (4 cases). CONCLUSIONS: PCR detection can rapidly identify more pathogens and even multi-pathogen infections. Therefore, PCR testing may improve pathogen detection in patients with suspected bloodstream infections, enabling targeted treatment of patients.

A novel polypeptide-modified fluorescent gold nanoclusters for copper ion detection.

Biomolecule-functionalized fluorescent gold nanocluster (AuNCs) have attracted a lot of attention due to good biocompatibility, stable physicochemical properties and considerable cost advantages. Inappropriate concentration of Cu2+ may cause a variety of diseases. In this study, AuNCs were synthesized in alkaline aqueous solution using bovine serum albumin (BSA) as a template. And then, the peptide CCYWDAHRDY was coupled to AuNCs. Furthermore, the fluorescence of synthesized CCYWDAHRDY-AuNCs response to Cu2+ was evaluated. As the results shown that the CCYWDAHRDY-AuNCs can sensitively detect Cu2+. After adding Cu2+ to the probe system, the fluorescence of the CCYWDAHRDY-AuNCs was quenched. The detection conditions were at pH 6 and 30 °C for 10 min, the linear relationship between Cu2+ concentration and fluorescence intensity were good in the range of 0.1 ~ 4.2 µmol/L. The regression equation was y = - 105.9x + 693.68, the linear correlation coefficient is 0.997, and the minimum detection limit was 52 nmol/L.

Salidroside alleviates liver inflammation in furan-induced mice by regulating oxidative stress and endoplasmic reticulum stress.

Furan is a genotoxic and carcinogenic toxicant formed during the food thermal processing. Our previous studies confirmed that salidroside (SAL) displayed excellent protective effects against furan-induced hepatotoxicity and inflammation, whereas the underlying mechanism was still unclear. In the current study, Balb/c mice were divided to the control group (CON), the furan model group (FUR8, 8 mg/kg BW furan for 30 days) and SAL intervention groups (SAL10/20/40, 8 mg/kg BW furan for 30 days + 10/20/40 mg/kg BW SAL from day 16 to day 30). The alleviative effects and the mechanisms of SAL against furan-induced liver inflammation in mice were investigated through oxidative stress (OS) and endoplasmic reticulum stress (ERS). Liver metabonomics data, molecular docking and Western-blotting results implied that SAL suppressed the activity and the high expression of hepatic CYP2E1, and alleviated liver OS induced by furan. Levels of key markers (GRP78, CHOP and Caspase-12) of ERS and proteins in IRE1α pathway of the UPR branch increased by furan were prominently reduced after SAL treatment. Levels of phosphorylated proteins JNK, ERK, p38, IKKα/ß, IκB and p65 in MAPK and NF-κB pathways were also suppressed by SAL. We further confirmed that SAL inhibited furan-induced inflammation by reducing the levels of NLRP3, ASC, Cleaved Caspase-1 and IL-1ß and decreasing the production of pro-inflammatory cytokines. Our results shed light into the alleviating mechanisms behind furan-induced liver inflammation, and suggested that SAL inhibited OS, ERS and related MAPK and NF-κB pathways and therefore inhibited the NLRP3 inflammasome activation, which may be its potential mechanism of alleviating liver inflammation.

MiR-193b-5p protects BRL-3A cells from acrylamide-induced cell cycle arrest by targeting FoxO3.

Acrylamide (AA), an important by-product of the Maillard reaction, has been reported to be genotoxic and carcinogenic. The present study employed miRNAs to investigate the toxic mechanism of AA and their role against AA toxicity. Deep sequencing of small RNA libraries was performed and miR-193b-5p was applied for further study. AA significantly reduced the level of miR-193b-5p and its ectopic expression promoted cell cycle G1/S transition and cell proliferation by upregulating the cyclin-dependent kinase regulator Cyclin D1 and downregulating the cyclin-dependent kinase inhibitor p21, while miR-193b-5p inhibitor led to the opposite results. Dual luciferase assay demonstrated miR-193b-5p regulated the expression of FoxO3 by directly targeting the FoxO3 3'-untranslated region (3'-UTR). Knockdown of FoxO3 induced cell cycle G1/S transition and cell proliferation, which was suppressed by the inhibition of miR-193b-5p but promoted by miR-193b-5p mimics. MiR-193b-5p inhibitor strengthened the effect of FoxO3, contrary to the effect of miR-193b-5p mimics. In conclusion, miR-193b-5p acted as a regulator of cell cycle G1/S transition and cell proliferation by targeting FoxO3 to mediate the expression of p21 and Cyclin D1.

Electrodialytic Desalination of Tobacco Sheet Extract: Membrane Fouling Mechanism and Mitigation Strategies.

In the papermaking industry (reconstituted tobacco), a large number of tobacco stems, dust, and fines are discharged in the wastewater. This high salinity wastewater rich in ionic constituents and nicotine is difficult to be degraded by conventional biological treatment and is a serious threat that needs to be overcome. Electrodialysis (ED) has proved a feasible technique to remove the inorganic components in the papermaking wastewater. However, the fouling in ion exchange membranes causes deterioration of membranes, which causes a decrease in the flux and an increase in the electrical resistance of the membranes. In this study, the fouling potential of the membranes was analyzed by comparing the properties of the pristine and fouled ion exchange membranes. The physical and chemical properties of the ion exchange membranes were investigated in terms of electrical resistance, water content, and ion exchange capacity, as well as studied by infrared spectroscopy (IR) spectra, scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) analyses. The results indicated that the membrane fouling is caused by two different mechanisms. For the anion exchange membranes, the fouling is mainly caused by the charged organic anions. For the cation exchange membrane, the fouling is caused by minerals such as Ca2+ and Mg2+. These metal ions reacted with OH- ions generated by water dissociation and precipitated on the membrane surface. The chemical cleaning with alkaline and acid could mitigate the fouling potential of the ion exchange membranes.

Antioxidant Activity and Transcriptomic Analysis of Se-Enriched Golden Oyster Mushroom Pleurotus citrinopileatus (Agaricomycetes).

Food enriched with organic selenium is considered as a good source for selenium supplementation. In the current research, we cultivated Pleurotus citrinopileatus with medium containing different levels of sodium selenate, evaluated the antioxidant activity, and sequenced the transcriptome of the Se-enriched mushroom. Selenium content in Se-enriched mushroom is dependent on selenium level in the surroundings. The ABTS total radical scavenging ability was not significantly different between selenium enriched mushroom and the control, though the total phenol content was increased in Se-enriched mushroom. Transcriptome sequencing showed a total of 1036 differentially expressed genes, including 987 upregulated genes and 49 downregulated genes. These differentially expressed genes are involved in 20 metabolic pathways, most of which are involved in carbon metabolism and amino acid biosynthesis, while many differentially expressed genes are in growth, plasma membrane, and protein binding. It needs to be noted that the sulfur metabolism and ABS transporters, which are closely related with selenium metabolism and transportation, are particularly enriched. The mushroom P. citrinopileatus has strong ability to uptake selenium from the surroundings, which modifies many biological pathways. This paper provides a theoretical reference for the development of Se-enriched fungal foods.

Toxicogenomic evaluation of liver responses induced by acrylamide and glycidamide in male mouse liver.

In current studies, histopathologic method, Agilent GeneChip hybridization and Western blot were used to investigate the toxicity of acrylamide (AA) and glycidamide (GA) in male mouse livers. The histopathologic results demonstrated that AA and GA could cause oxidative damage to mouse liver. Middle dose of GA and AA (50 mg/kg b.w./day) could significantly up-regulate the expression of cytochrome P450, as well as genes related to oxidative injury, cancer and inflammation, and significantly down-regulate the expression of genes related to anti-apoptosis, antioncogene and fatty acid synthesis. Middle and high dose (75 mg/kg b.w./day) of GA and AA could both down-regulate the expression of hepatic anti-oncogene Bcl2 and up-regulate the expression of cancer-related gene Rad51 and EGFR protein. The expression of anti-oncogene P21 induced by AA and GA was decreased. Our current study demonstrated that the oxidative damage, immune injury and carcinogenicity of mouse liver samples could be induced by AA and GA at histopathological, entire genome and protein levels.

A Comparison Study of Frying Conditions on Furan Formation in 3 Potato Varieties.

Furan, a typical food contaminant formed by heating process, is classified as a possible carcinogen to humans. Many factors lead to the formation of furan in food processing. In our present study, 3 potato varieties, white potato, sweet potato, and purple potato were selected to investigate the effect of thermal processing temperature and time on furan formation. The results showed that the formation of furan was highly correlated with frying temperature and time. Among the 3 potato varieties, sweet potato resulted in the highest furan concentration when fried at 200 °C for 5 min. In addition, the frying temperature and time also influenced the water activity and the color of the 3 kinds of potato slices, which had significant correlation with the formation of furan. Furan concentration decreased along with the increasing of water activity in the 3 potato varieties and the changes presented regression relationships. Meanwhile, there was an inverse correlation between furan content and color changes in the 3 potato varieties. The level of furan decreased as total color changes (ΔE) increased and the changes also presented regression relationships. These results could be used to estimate the possibility of furan formation in the 3 varieties of potato slices systems.

Role of plant polyphenols in acrylamide formation and elimination.

Acrylamide found in thermal-treated foods has led to an intensive and persistent research effort, since it is a neurotoxic, genotoxic and probable carcinogenic compound to humans. Plant polyphenols are the most abundant antioxidants in human diet. Several researches indicated that the polyphenols affected the acrylamide formation during heating. However, the controversial effects of the polyphenols on acrylamide formation were related to their structure, concentrations, and antioxidant capacity, as well as reaction condition. Polyphenols can inhibit acrylamide formation through trapping of carbonyl compounds and preventing against lipid oxidation, while some special polyphenols can enhance the acrylamide content by providing carbonyl groups, accelerating the conversion from 3-aminopropionamide (3-APA) to acrylamide and inhibiting acrylamide elimination. This review concludes the effects of polyphenols in the Maillard reaction and food systems conducted so far, aimed to give an overview on the role of plant polyphenols in acrylamide formation and elimination.

Protective effect of allicin against glycidamide-induced toxicity in male and female mice.

Acrylamide is known to be a neurotoxic, genotoxic, and carcinogenic compound. Glycidamide has a close relationship to the toxic mechanism of acrylamide. In order to explore the toxic mechanism of acrylamide, we further discussed the effects of oral administration of allicin on glycidamide-induced toxicity by determining the hematological parameters like AST, ALT, LDH, BUN, creatinine, ROS, and 8-OHdG, and biochemical parameters such as MDA, MPO, SOD, GST and GSH in the kidney, liver, brain and lung of male and female mice for the first time. We found that the same dose of glycidamide had more toxic effects and damage effects to the mice compared to the previous study of acrylamide. It could markedly increase the level of AST, ALT, LDH, BUN, ROS, 8-OHdG, MDA, MPO while decrease the SOD, GST and GSH. However, our data showed the oral administered allicin with a concentration of 5, 10, and 20 mg/kg b.w./day could significantly decrease the damage indexes of AST, ALT, LDH, BUN, ROS, 8-OHdG, MDA, and MPO, while increase the antioxidant indicators of SOD, GST and GSH. Thus allicin could be used as an effective dietary supplement for the chemoprevention of glycidamide genotoxicity internally, and to prevent the tissue damage and toxicity induced by glycidamide.

Protective effects of phillyrin on H2O 2-induced oxidative stress and apoptosis in PC12 cells.

Oxidative stress is a major component of harmful cascades activated in neurodegenerative disorders. We sought to elucidate possible effects of phillyrin, an active constituent isolated from the Chinese medicinal herb Forsythia suspense, on hydrogen peroxide (H2O2)-induced cell death and determine the underlying molecular mechanisms in neuron-like PC12 cells. By MTT assay and lactate dehydrogenase (LDH) leakage assay, we found that phillyrin treatment effectively protected PC12 cells against H2O2-induced cell damage. H2O2 exposure induced oxidative stress in PC12 cells, as revealed by enhanced oxidative stress and decreased activities of antioxidative enzymes, which were inhibited by phillyrin pretreatment. ROS activated mitochondria-dependent apoptosis. The anti-apoptotic effects of phillyrin were also confirmed by acridine orange/ethidium bromide (AO/EB) staining. Mitochondrial membrane potential decrease, cytochrome c release, caspases activation, activation of AIF and Endo G were observed in H2O2-treated cells by rhodamine 123 or western blot. Interestingly, phillyrin effectively suppressed these changes. Moreover, phillyrin could inhibit H2O2-induced up-regulation of Bax/Bcl-2 ratio. In conclusion, phillyrin effectively inhibited H2O2-induced oxidative stress and apoptosis in PC12 cells.

Potential protective effects of oral administration of allicin on acrylamide-induced toxicity in male mice.

Acrylamide (AA) forms during the heating of starchy foods at high temperature, and is regarded as a potential genotoxic carcinogen. However, with the worldwide concern about the carcinogenicity of AA, how to reduce the toxicity of AA has become a hot research topic. In this study, we further discussed the effects of oral administration of allicin on AA-induced toxicity by determining the hematological, biochemical and immunological parameters in the serum, kidney, liver, and brain of male mice. Our data showed that the orally administered allicin of 5, 10, and 20 mg kg⁻¹ bw d⁻¹ could significantly decrease thiobarbituric reactive substances (TBARS) and myeloperoxidase (MPO) levels, and simultaneously remarkably increased the superoxide dismutase (SOD) activity, glutathione S-transferase (GST) and glutathione (GSH) levels in the kidney, liver, and brain of the AA-treated mice. Furthermore, oral administration of allicin not only significantly decreased aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, interleukin (IL)-6, reactive oxygen species (ROS), and 8-hydroxy-desoxyguanosine (8-OHdG), but also increased interleukin (IL)-10 in the serum of AA-treated mice. Therefore, it was concluded that oral administration of allicin had a significant in vivo protective effect against the AA induced toxicity.