Search

Introduction: To identify novel pathways involved in the pathogenesis of ketosis, an isobaric tag for relative and absolute quantitation/mass spectrometry was used to define differences in protein expression profiles between healthy dairy cows and those with clinical or subclinical ketosis.

Simple Summary: Colorectal cancer (CRC) is one of the most common cancers, which has a poor prognosis and is prone to recurrence and metastasis. DPP7 is a prolyl peptidase, which is an enzyme characterized by the feature of cleaving proline-containing peptides. We found that the expression level of DPP7 in CRC samples was significantly higher than that in adjacent non-tumor tissues by analyzing public colorectal cancer data and surgical specimens of CRC patients. Moreover, the increased expression of DPP7 is correlated with a higher stage of cancer and shorter overall survival, indicating the diagnostic value of DPP7 for CRC. Furthermore, functional annotations indicated that DPP7 is involved in neuroactive ligand–receptor interaction and olfactory transduction signaling. Our data demonstrated that DPP7 is a promising diagnostic and prognostic biomarker as well as a new therapeutic target for CRC. Colorectal cancer has a poor prognosis and is prone to recurrence and metastasis. DPP7, a prolyl peptidase, is reported to regulate lymphocyte quiescence. However, the correlation of DPP7 with prognosis in CRC remains unclear. With publicly available cohorts, the Wilcoxon rank-sum test and logistic regression were employed to analyze the relationship between DPP7 expression and the clinicopathological features of CRC patients. Specific pathways of differentially expressed genes were determined through biofunctional analysis and gene set enrichment analysis (GSEA). qPCR and immunohistochemical staining were used to determine DPP7 expression levels in surgical specimens. The public dataset and analysis of the biospecimens of CRC patients revealed that DPP7, in the CRC samples, was expressed significantly higher than in non-tumor tissues. Moreover, increased DPP7 was significantly associated with a higher N stage, lymphatic invasion, and shorter overall survival. Functionally, DPP7 is involved in neuroactive ligand–receptor interaction and olfactory transduction signaling. We identified a series of targeted drugs and small-molecule drugs with responses to DPP7. To conclude, DPP7 is a valuable diagnostic and prognostic biomarker for CRC and considered as a new therapeutic target. [ABSTRACT FROM AUTHOR]

Acute mastitis is one of the main reasons why breastfeeding women stop breastfeeding, and medication should be used with caution. Considering the uncertainty of mastitis infection and the indications of antibiotic use, as well as the problem of drug resistance and the safety of medication during lactation, probiotics have become an alternative treatment choice. However, a meta-analysis of the effects of probiotics in preventing and treating lactational mastitis is still lacking. Therefore, we searched six electronic databases and the sites of clinical trial registration, a total of six randomized controlled trials were included in this meta-analysis, which showed that oral probiotics during pregnancy can reduce the incidence of mastitis (RR: 0.49, 95% CI: 0.35 to 0.69; p<0.0001). After oral administration of probiotics, the counts of bacteria in the milk of healthy people and mastitis patients were both significantly reduced (in healthy people: MD: -0.19, 95% CI: -0.23 to -0.16, p<0.00001; in mastitis patients: MD: -0.89, 95% CI: -1.34 to -0.43, p = 0.0001). These indicate that to a certain extent, probiotics are beneficial in reducing the incidence rate of mastitis during lactation and some related mastitis symptoms. However, high-quality multicenter clinical trials are still needed to support this result. [ABSTRACT FROM AUTHOR]

Background and objective: The application of curcumin is limited by its instability. Mono‐carbonyl analogues of curcumin (MCACs) are structurally stable, yet the intermediate bridging ketones in their skeletons account for increased toxicity. This study aimed to synthesize and screen MCACs that exhibit low cytotoxicity and high antioxidant ability, and the effects of MCACs on experimental periodontitis were also investigated. Materials and methods: The cytotoxicity of MCACs on MC3 T3‐E1 was determined by MTT assay. The antioxidant capacity was investigated by the cell viability against H2O2‐induced damage and the level of reactive oxygen species (ROS) and malondialdehyde (MDA). The localization and protein expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) was detected by immunofluorescence and western blot, respectively. In addition, MCAC was intragastrically administrated in rats with ligature‐induced experimental periodontitis. The effects were assessed by bone resorption, as well as the immunohistology staining of inflammatory and oxidative stress markers. Results: MCACs with cyclopentanone and containing pyrone showed lower toxicity than natural curcumin were synthesized (1A‐10A, 1H‐10H), among which, 1A exhibited the most potent cytoprotective effect against H2O2‐induced damage. Such effects could be explained by the reduced MDA and ROS level, possibly through the nucleus translocation of Nrf2 and the induction of HO‐1. Micro‐CT results further indicated that 1A significantly reduced bone loss, along with an increased level of Nrf2 and HO‐1, and decreased TNF‐α and IL‐1β. Conclusion: The present study has synthesized a novel antioxidant MCAC 1A with good biosafety and stability. MCAC 1A could serve as a host response modulator with preventive and protective effects on periodontitis. [ABSTRACT FROM AUTHOR]

This work demonstrates a novel chemosensor, SPTPA, that exhibits fluorescence and colorimetric dual sensing of hypochlorite with an ICT ON strategy. Additionally, the chemosensor successfully detected and imaged endogenous hypochlorite in living cells, various types of bacteria, and zebrafish. [ABSTRACT FROM AUTHOR]

Background and objective: Bone remodeling during orthodontic treatment is achieved by the osteogenesis of human periodontal ligament cells (PDLCs) subjected to mechanical loadings. Transcriptional co‐activator with PDZ‐binding motif (TAZ) mediates bone remodeling in response to extracellular mechanical signals. This study aims to investigate the role of TAZ in osteogenesis of PDLCs under tensile strain. Materials and methods: A uniaxial cyclic tensile stress (CTS) at 12% elongation and 6 cycles/min (5 s on and 5 s off) was applied to PDLCs. The osteogenic differentiation was determined by the protein and gene expressions of osteogenic markers using qRT‐PCR and Western blot, respectively, and further by alkaline phosphatase (ALP) activity and Alizarin Red S staining. The interaction of TAZ with core‐binding factor α1 (Cbfα1) was examined by co‐immunoprecipitation. The immunofluorescence histochemistry was used to examine the nucleus aggregation of TAZ and the reorganization of actin filaments. Moreover, small interfering RNA‐targeting TAZ (TAZsiRNA) was used for TAZ inhibition and Y‐27632 was employed for Ras homologue‐associated coiled‐coil protein kinase (ROCK) signaling blockage. Results: CTS clearly stimulated the nucleus accumulation of TAZ and its interaction with Cbfα1. CTS‐induced osteogenesis in PDLCs was significantly abrogated by the infection with TAZsiRNA, as shown by the decreased stained nodules and protein expressions of Cbfα1, collagen type I, osterix, and osteocalcin, along with the inhibition of β‐catenin signaling. Moreover, ROCK inhibition by Y‐27632 hindered TAZ nucleus aggregation and its binding with Cbfα1, which subsequently lead to the decreased osteoblastic differentiation of PDLCs. Conclusions: Taken together, we propose that TAZ nucleus localization and its interaction with Cbfα1 are essential for the CTS‐induced osteogenic differentiation in PDLCs. And such TAZ activation by CTS could be mediated by ROCK signaling, indicating the pivot role of ROCK‐TAZ pathway for PDLCs differentiation. [ABSTRACT FROM AUTHOR]

Copper (Cu) is an important microelement for the maintenance of normal metabolism of dairy cows and a variety of enzymic composition. When Cu deficiency is occurred in dairy cows, it’ll be accompanied by many diseases. The main objective of the present study was to explore the correlation between Cu deficiency and oxidative stress of lactating dairy cows and evaluate early-warning index for Cu deficiency. There were divided into two groups based on serum Cu levels: a Cu deficiency group and a control group. Serum levels of ceruloplasmin (CP), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), and Cu were analysed. The results showed that CP levels in the Cu deficiency group were significantly lower than in the control group, while T-AOC levels were significantly higher, but there were no significant differences between SOD and GSH-PX levels. Pearson correlation analysis showed that serum CP levels were very significantly positively correlated with Cu deficiency, while serum T-AOC levels were very significantly negatively correlated and SOD and GSH-PX serum levels showed no correlations. Logistic regression analysis showed that CP was a risk factor for Cu deficiency, ROC analysis showed that CP had diagnostic value for Cu deficiency, with a critical value of 13.7 U/l. Hence, CP and T-AOC levels in lactating cows showed strong correlations to Cu deficiency, indicating that serum CP can be used to predict Cu deficiency. [ABSTRACT FROM AUTHOR]

To understand the differences in metabolic changes between cows with ovarian inactivity and estrus cows, we selected cows at 60–90 days postpartum from an intensive dairy farm. According to clinical manifestations, B-ultrasound scan, rectal examination, 10 cows were assigned to the estrus group (A) and 10 to the ovarian inactivity group (B). All plasma samples were analyzed by 1 H-nuclear magnetic resonance spectroscopy to compare plasma metabolomic profiles between the groups. We used multivariate pattern recognition to screen for different metabolites in plasma of anestrus cows. Compared with normal estrous cows, there were abnormalities in 12 kinds of metabolites in postpartum cows with ovarian inactivity (|r|> 0.602), including an increase in acetic acid (r = −0.817), citric acid (r = −0.767), and tyrosine (r = −0.714), and a decrease in low-density lipoprotein (r = 0.820), very low–density lipoprotein (r = 0.828), lipids (r = 0.769), alanine (r = 0.816), pyruvate (r = 0.721), creatine (r = 0.801), choline (r = 0.639), phosphorylcholine (r = 0.741), and glycerophosphorylcholine (r = 0.881). These metabolites were closely related to abnormality of glucose, amino acid, lipoprotein and choline metabolism, which may disturb the normal estrus. The decrease in plasma creatine and the increase in tyrosine were new changes for ovarian inactivity of postpartum cows. The decrease in plasma creatine and choline and the increase in tyrosine and p-hydroxyphenylalanine in cows with ovarian inactivity provide new directions for research on the mechanism of ovarian inactivity in cows. [ABSTRACT FROM AUTHOR]

Progesterone (P4) is a steroid gonadal hormone that is mainly produced from the corpus luteum and placenta and has various biological functions, especially reproductive regulation. It is important to establish a specific and sensitive P4 enzyme-linked immunosorbent assay (ELISA) for the study of ovary activity and reproductive disorders. Therefore, we prepared a monoclonal antibody (MAb) in a completed antigen (11α-OH-P4-HS-OVA). Based on the MAb and our previously prepared completed antigen, a highly specific and sensitive ELISA was developed. In the present study, a competitive ELISA for the determination of P4 was described in dairy cow milk. It was found that P4 concentration in milk samples from five pregnant cows was significantly higher than that from five estrus cows. The diagnosis rate for pregnancy and non-pregnancy in 54 dairy cows were 93.3% and 95.8%, respectively, at 19 to 23 days after pregnancy by detecting milk P4 concentration. In summary, the developed ELISA is a potential tool for P4 research and offers an alternative, simple, rapid technique for detecting P4, especially in future large clinical investigations on pregnancy identification and reproductive disorders in dairy farms in China. [ABSTRACT FROM AUTHOR]

The upper-level jet stream, a narrow band of maximum wind speed in the mid-latitude westerlies, exerts a considerable influence on the global climate by modulating the transport and distribution of momentum, heat and moisture. In this study by using four high-resolution models in the Paleoclimate Modelling Intercomparison Project phase 3, the changes of position and intensity of the northern hemisphere westerly jet at 200 hPa in summer during the mid-Holocene (MH), as well as the related mechanisms, are investigated. The four models show similar performance on the westerly jet. At the hemispheric scale, the simulated westerly jet has a poleward shift during the MH compared to the preindustrial period. The warming in arctic and cooling in the tropics during the MH are caused by the orbital changes of the earth and the precipitation changes, and it could lead to the weakened meridional temperature gradient and pressure gradient, which might account for the poleward shift of the westerly jet from the thermodynamic perspective. From the dynamic perspective, two maximum centers of eddy kinetic energy are simulated over the North Pacific and North Atlantic with the north deviation, which could cause the northward movement of the westerly jet. The weakening of the jet stream is associated with the change of the Hadley cell and the meridional temperature gradient. The largest weakening is over the Pacific Ocean where both the dynamic and the thermodynamic processes have weakening effects. The smallest weakening is over the Atlantic Ocean, and it is induced by the offset effects of dynamic processes and thermodynamic processes. The weakening over the Eurasia is mainly caused by the dynamic processes. [ABSTRACT FROM AUTHOR]

• Highly expressed CXCL1-3, 5, 8 exert an important effect on CRC oncogenesis. • Highly expressed CXCL10-11 serve as positive prognostic factors for CRC patients. • CXCL9-11 may recruit anti-tumor CD8+ T cells and NK cells in CRC patients. The C-X-C motif (CXC) chemokines play an important role in inflammatory processes and angiogenesis and are also associated with tumor development, progression and metastasis. They can be either promoting or inhibiting factors in colorectal cancers (CRC). The expression patterns and prognostic values of the CXC family still need further investigation. In this study, we investigated data related to transcription, translation, survival and tumor immune infiltration for CXC chemokines in patients with CRC from the ONCOMINE, GEPIA, cBioPortal, HPA and TIMER databases. We found that the expression levels of CXCL1-3, CXCL5, and CXCL8 were higher in CRC tissues than in colorectal tissues. Expression among stages significantly varied for CXCL1-3 and CXCL9-11. The survival analysis revealed that high transcriptional levels of CXCL4 and CXCL9-11 could serve as positive prognostic factors for patients with CRC. CXCL9-11 were highly associated with CD8+ T cells and natural killer (NK) cells in the tumor immune infiltration analysis, indicating their role in the antitumor immune response. This study implies that CXCL1-3, CXCL5, and CXCL8 are important factors during CRC oncogenesis and that CXCL9-11 could be new biomarkers for the prognosis of CRC. [ABSTRACT FROM AUTHOR]

A bacilliform virus was isolated from yellow catfish in China. This virus can directly adapt in cultures of EPC cells. The virus particles, which were rod-shaped approximately 120 nm long and 20 nm wide, were visible in the cytoplasm of EPC cells. The full-length genome of this virus is 26,985 nt. The genome contains four open reading frames that encode polyprotein1ab, spike glycoprotein, M protein, and N protein. There was a putative slippery sequence 14861UUUAAAC14867, which could be modeled into an RNA pseudoknot structure. The predicted amino acid sequence of pp1ab, S, M, and N genes shares 8.7%–40.2% homology with those of the two known Bafinivirus strains—WBV and FHMNV. Based on the viral morphology, genome organization, and sequence homology, this newly identified bacilliform virus appears to be Piscanivirus. To the best of our knowledge, this is the first report of Piscanivirus in yellow catfish and Piscanivirus in China. • A new bacilliform virus isolated from yellow catfish collected in China was dentified. • The identified virus can directly adapt in cell culture. • The virus particle is rod-shaped approximately 120 nm long and 20 nm wide in the cytoplasm. • The full-length genomic sequence of the virus is 26,985 nt. The sequence in region 1187-2214 nt is hypervariable. • The newly identified virus was a new member in the subfamily Piscanivirinae. [ABSTRACT FROM AUTHOR]

Acid-alkaline balance plays a crucial role in all biological processes. Accordingly, monitoring pH changes will help us to understand the functional status of these physiological and pathological processes. Though fluorescent probes may be a useful tool for detecting pH changes, and there are many limitations to currently available probes, such as background interference, potential cytotoxicity, and poor cell permeability, which call for a solution urgently. In this work, a rhodamine-derived colorimetric and ratiometric sensor (Rh–HN) was fabricated for monitoring pH change via the mechanism of fluorescence resonance energy transfer (FRET). Rh–HN has been shown to possess several advantages over other probes, such as high sensitivity, outstanding permeability, and low toxicity. Besides, the fluorescence intensity ratio (F 526 /F 592) of Rh–HN displays a pH-sensitive response from 2.0 to 7.5 (p K a = 5.05) and linear response from pH 3.8 to 6.4, which was desirable for mapping pH change in the biological systems. Besides, the results indicated that Rh–HN generated a pH-dependent response regulated by switchable forms between closed and opened spirolactam ring. Overall, Rh–HN has accomplished sensing and mapping of pH in living cells, bacteria, and zebrafish. Those results demonstrated that the great potential of Rh–HN in sensing and visualizing pH in the living biosystem. Image 1 • A Rhodamine-derived sensor Rh–HN was developed to visualize and monitor pH variation with p K a = 5.05. • Rh–HN exhibited reversible colorimetric/ratiometric responses to pH by switching of closed and opened spirolactam. • Response mechanism of Rh–HN was revealed by density functional theory calculation. • Rh–HN has successfully accomplished pH mapping in living cells, bacteria and zebrafish. [ABSTRACT FROM AUTHOR]

Tracking and quantifying hypochlorite (ClO−) in biological systems and environments remain challenging tasks, and many efforts have been made to improve ClO− recognition performance by modifying the sensor structure. In this study, a pre-designed coumarin/furanohydrazide-based sensor (CMFH) with the coumarin moiety as the building block (fluorogen) was rationally prepared as a ratiometric and colorimetric chemosensor for ClO− recognition. As expected, CMFH demonstrated excellent sensitivity and selectivity for ClO− detection. The fluorescence signal ratio (F 466 / F 556) showed strong ClO− dependency, and the sensor exhibited ultrafast detection (within 60 s) and a low detection limit of 563 nM. Due to its low cytotoxicity and good tissue permeability, CMFH was demonstrated as a dual-channel sensor for ClO− bioimaging and visualization in cells, zebrafish, and even bacteria. Furthermore, CMFH- loaded paper strips were successfully applied to the colorimetric and fluorescent visualization of ClO−. The results demonstrate that CMFH has potential application value for tracking ClO− in various biosystems and environments. [Display omitted] • A concise CMFH chemosensor has been employed to identify ClO− with high selectivity. • CMFH can respond to ClO− with ratiometric and colorimetric responses strategy. • CMFH can trace and map ClO− in living cells, P. aeruginosa and zebrafish. • Visual recognition of fluorescence and color of ClO− can be realized on a paper strip. [ABSTRACT FROM AUTHOR]

Osseointegration commences with foreign body inflammation upon implant placement, where macrophages play a crucial role in the immune response. Subsequently, during the intermediate and late stages of osseointegration, mesenchymal stem cells (MSCs) migrate and initiate their osteogenic functions, while macrophages support MSCs in osteogenesis. The utilization of ferroelectric P(VDF-TrFE) covered ITO planar microelectrodes facilitated the simulation of various surface charge to investigate their effects on MSCs' osteogenic differentiation and macrophage polarization and the results indicated a parabolic increase in the promotional effect of both with the rise in piezoelectric coefficient. Furthermore, the surface charge with a piezoelectric coefficient of -18 exhibited the strongest influence on the promotion of M1 polarization of macrophages and the promotion of MSCs' osteogenic differentiation. The impact of macrophage polarization and MSC osteogenesis following the interaction of macrophages affected by surface charge and MSC was ultimately investigated. It was observed that macrophages affected by the surface charge of -18 piezoelectric coefficient still exerted the most profound induced osteogenic effect, validating the essential role of M1-type macrophages in the osteogenic differentiation of MSCs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Xu, Huang, Chen, Cheng, Wang and Chen.)

This experiment investigates how the miR-99b/let-7e/miR-125a cluster regulates the mechanism of NR6A1 involved in the invasive and metastatic effects of pancreatic cancer (PCa). Bioinformatics prediction and dual luciferase reporter gene assay were applied to verify the targeted relationship between miR-99b/let-7e/miR-125a and NR6A1. ASPC1 cells underwent transfection with lentiviruses to overexpress miR-99b/let-7e/miR-125a (individual or together) to explore functions of miR-99b/let-7e/miR-125a cluster governing NR6A1 in PCa. The detection of tumorigenesis was verified by tumor formation assay in nude mice in vivo, and mouse models of liver metastasis of PCa observed cell metastasis of PCa. MiR-99b/let-7e/miR-125a cluster was screened for differential expression in PCa. NR6A1 was confirmed as a target gene of the miR-99b/let-7e/miR-125a cluster. Findings demonstrated that overexpression of the miR-99b/let-7e/miR-125a cluster inhibited cell invasion, metastasis, proliferation, and tumorigenesis in PCa. Conversely, overexpressed NR6A1, a crucial gene in the miR-99b/let-7e/miR-125a cluster, promoted cell invasion, migration, and proliferation in PCa. Moreover, the overexpression of the miR-99b/let-7e/miR-125a cluster inhibited liver metastases and tumor formation. Thus, the study concludes that the miR-99b/let-7e/miR-125a cluster impedes the invasion and metastasis of PCa cells via targeting the NR6A1 gene., Competing Interests: None., (AJCR Copyright © 2024.)

Structural parameters of the implants such as shape, size, and porosity of the pores have been extensively investigated to promote bone tissue repair, however, it is unknown how the pore interconnectivity affects the bone growth behaviors in the scaffolds. Herein we systematically evaluated the effect of biodegradable bioceramics as a secondary phase filler in the macroporous networks on the mechanical and osteogenic behaviors in sparingly dissolvable bioceramic scaffolds. The pure hardystonite (HT) scaffolds with ∼550 & 800 μm in pore sizes were prepared by digital light processing, and then the Sr-doped calcium silicate (SrCSi) bioceramic slurry without and with 30 % organic porogens were intruded into the HT scaffolds with 800 μm pore size and sintered at 1150 °C. It indicated that the organic porogens could endow spherical micropores in the SrCSi filler, and the invasion of the SrCSi component could not only significantly enhance the compressive strength and modulus of the HT-based scaffolds, but also induce osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The pure HT scaffolds showed extremely slow bio-dissolution in Tris buffer after immersion for 8 weeks (∼1 % mass decay); in contrast, the SrCSi filler would readily dissolve into the aqueous medium and produced a steady mass decay (>6 % mass loss). In vivo experiments in rabbit femoral bone defect models showed that the pure HT scaffolds showed bone tissue ingrowth but the bone growth was impeded in the SrCSi-intruded scaffolds within 4 weeks; however, the group with higher porosity of SrCSi filler showed appreciable osteogenesis after 8 weeks of implantation and the whole scaffold was uniformly covered by new bone tissues after 16 weeks. These findings provide some new insights that the pore interconnectivity is not inevitable to impede bone ingrowth with the prolongation of implantation time, and such a highly biodegradable and bioactive filler intrusion strategy may be beneficial for optimizing the performances of scaffolds in bone regenerative medicine applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

In recent years, there has been a significant increase in the incidence of Breast cancer (BC), making it the most common cancer among women and a major threat to women's health. Consequently, there is an urgent need to discover new and effective strategies for treating BC. Ferroptosis, a novel form of cell death characterized by the accumulation of iron-dependent lipid reactive oxygen species, has emerged as a distinct regulatory pathway separate from necrosis, apoptosis, and autophagy. It is widely recognized as a crucial factor in the development and progression of cancer, offering a promising avenue for BC treatment. While significant progress has been made in understanding the mechanisms of ferroptosis in BC, drug development is still in its early stages. Numerous compounds, including phytochemicals derived from dietary sources and medicinal plants, as well as synthetic drugs (both clinically approved medications and laboratory reagents), have shown the ability to induce ferroptosis in BC cells, effectively inhibiting tumor growth. This comprehensive review aims to examine in detail the compounds that target ferroptosis in BC and elucidate their potential mechanisms of action. Additionally, the challenges associated with the clinical application of ferroptosis-inducing drugs are discussed, offering valuable insights for the development of novel treatment strategies for BC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Chen, Yu, Song, Jin and Gao.)

Objective: Tamoxifen is an effective anti-tumor medicine, but evidence has been provided on tamoxifen-related inflammation as well as its impact on gut microbiota. In this study, we aimed to investigate tamoxifen-induced gut microbiota and inflammation alteration., Methods: We established a BC xenograft mouse model using the MCF-7 cell line. 16S rRNA gene sequencing was used to investigate gut microbiota. qRT-PCR, western blotting, and cytometric bead array were used to investigate inflammation-related biomarkers. Various bioinformatic approaches were used to analyze the data., Results: Significant differences in gut microbial composition, characteristic taxa, and microbiome phenotype prediction were observed between control, model, and tamoxifen-treated mice. Furthermore, protein expression of IL-6 and TLR5 was up-regulated in tamoxifen-treated mice, while the mRNA of Tlr5 and Il-6, as well as protein expression of IL-6 and TLR5 in the model group, were down-regulated in the colon. The concentration of IFN-γ, IL-6, and IL12P70 in serum was up-regulated in tamoxifen-treated mice. Moreover, correlation-based clustering analysis demonstrated that inflammation-negatively correlated taxa, including Lachnospiraceae-UCG-006 and Anaerotruncus , were enriched in the model group, while inflammation-positively correlated taxa, including Prevotellaceae&#95;UCG&#95;001 and Akkermansia , were enriched in the tamoxifen-treated group. Finally, colon histologic damage was observed in tamoxifen-treated mice., Conclusion: Tamoxifen treatment significantly altered gut microbiota and increased inflammation in the breast cancer xenograft mice model. This may be related to tamoxifen-induced intestinal epithelial barrier damage and TLR5 up-regulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Gao, Chen, Wang, Xu, Yu, Jin, Song and Zhu.)

Background: Androgen receptor (AR) is becoming an important factor in the pathogenesis of breast cancer. Traditional Chinese medicine (TCM) is widely used in treating breast cancer patients. Triple-negative breast cancer (TNBC) is a subtype of breast cancer, which has worse prognosis than other subtypes. Herein, through this retrospective study, we summarize the therapeutic implications of AR and TCM in TNBC., Methods: The clinical and pathological data of TNBC patients who had undergone surgery at The First Affiliated Hospital of Zhejiang Chinese Medical University from 2017 to 2019 were collected and examined. The t -test, chi-square test, logistic regression model, and Kaplan-Meier survival estimates were used to analyze the data., Results: We identified 823 early breast cancer patients from January 2017 to December 2019, of whom 92 (11.2%) were pathologically confirmed to have TNBC. We excluded 5 patients according to the inclusion and exclusion criteria. In relation to the remaining 87 patients, 33 (37.9%) were AR positive. In the TNBC patients, positive AR expression was correlated with an older age (P=0.006), a higher weight (P=0.006), and lower Ki-67 expression (P=0.031). After a median follow-up time of 37 months (range, 24-60 months), 13 cases of relapse and metastasis (14.9%) were observed. We found that relapse and metastasis were correlated with being unmarried [P=0.004; hazard ratio (HR) =0.105; 95% confidence interval (95% CI): 0.023-0.487], nonporous (P=0.046; HR =0.209; 95% CI: 0.045-0.971), and negative AR expression (P=0.042; HR =1.223; 95% CI: 0.049-1.012). The AR-positive TNBC patients had better disease-free survival (DFS) than the AR-negative TNBC patients 2-5 years after surgery (P<0.05). TCM was an effective treatment for TNBC (P<0.001; HR =51.682; 95% CI: 6.660-401.025). In the AR-negative group, patients who received the TCM treatment tended to have a better DFS than those who did not receive the TCM treatment (P<0.001; HR =34.832; 95% CI: 4.448-272.756); however, no such difference was found in the AR-positive group., Conclusions: The TNBC patients with positive AR tended to have a low expression of Ki-67 and a better prognosis than AR negative TNBC patients. TCM is an effective treatment and has slight side effects., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-22-508/coif). The authors have no conflicts of interest to declare., (2022 Gland Surgery. All rights reserved.)

Aim: We performed a systematic review and meta-analysis to evaluate the efficacy and safety of microwave ablation (MWA) for benign breast lesions., Material and Methods: PubMed, Embase, Web of Science, Cochrane Library databases, China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform databases were searched., Results: A total of 10 studies were included, giving a sample size of 1241 patients and 2729 benign breast lesions. The first complete ablation success rate was 96%. The volume reduction ratio (VRR) after 3/6/12 months was 47.4%, 62.1%, and 85.8%, respectively. After 12 months, the lesion disappearance rate was 53.6%, and the efficiency rate was 99%. The rate of excellent cosmesis was 88% and the rate of good cosmesis was 10%. The complication rate was 2%., Conclusions: MWA is safe and effective for treating benign breast lesions. It can be a promising minimally invasive choice for benign breast lesions., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Fundacja Videochirurgii.)

Background: An elevated level of olfactomedin-like-2A ( OLFML2A ) is unfavorable for female breast cancer patients. Patients with a high mRNA level of OLFML2A receive a poor prognosis. Therefore, we speculate that inhibiting the expression of this gene may be beneficial to breast cancer patients. We previously found that silencing the OLFML2A gene by using mRNA interference significantly inhibited proliferation and migration in triple-negative breast cancer (TNBC) cells., Methods: Cell activity and proliferation were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Celigo analyses. Cell migration and invasion were determined by wound-healing and transwell invasion assays. The mechanism of the inhibition of a small hairpin RNA that targets OLFML2A (sh OLFML2A ) was determined by using a GeneChip array, real-time quantitative PCR (RT-qPCR), and western blot analysis., Results: Gene silencing by sh OLFML2A induces apoptosis by promoting S phase arrest in TNBC cells. In addition, sh OLFML2A decreased the progression of epithelial-mesenchymal transition (EMT). Additionally, microarray analysis showed that sh OLFML2A significantly upregulated 428 genes and downregulated 712 genes. These significantly changed genes regulated DNA synthesis, chromosome alignment, microtubules and the cytoskeleton, cell movement, the cell cycle, cell necrosis, and apoptosis because they promoted G2/M DNA damage checkpoint regulation and p53 signaling, and because they inhibited integrin, hepatocyte growth factor (HGF), nerve growth Factor (NGF), and other tumor-promoting signaling pathways., Conclusions: sh OLFML2A reduces cell proliferation, migration, and invasion and promotes cell apoptosis. Therefore, the results of the present study suggest that OLFML2A is a potential therapeutic target for TNBC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-757/coif). All authors report that this work was supported by The National Natural Science Foundation of China (No. 82074438), the Natural Science Foundation of Zhejiang Province (No. LY18H270006), and the Zhejiang Province Traditional Chinese Medicine Scientific Research Foundation (No. 2016ZQ015). The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Bioactive molecules play a vital role in the process of regulating the redox balance in the intracellular environment, especially in maintaining the function of organelles. To explore the association and function of bioactive molecules in organelles, it is essential to develop a chemosensor tool that uses multiresponse fluorescence signals to distinguish between and track two related bioactive molecules in organelles. However, the development of sensors with multiresponse functions is still a challenging task. Herein, we present a unique and practical single chemosensor ( Mito-CTC ) that can monitor HClO (as an oxidative substance) and H 2 S (as a reductive substance) in mitochondria (organelle targeting) with multiresponse fluorescence signals. The response of the sensor to HClO and H 2 S changes from red to green and blue channel emission simultaneously, respectively, thereby providing a specific signal response to reductive/oxidative substances in the mitochondria. Using a single chemosensor, we have realized multichannel bioimaging of the exogenous and endogenous HClO and H 2 S in cellular mitochondria. Additionally, the excellent properties of the sensor Mito-CTC can be used to reveal the relationship between HClO and H 2 S in mitochondria. Meanwhile, Mito-CTC has been endowed with the ability to image in bacteria and zebrafish attributed to the good permeability and low cytotoxicity. Expectantly, drug-induced liver injury (DILI) caused by fluoxetine (an antidepressant drug) and the degree of drug-induced toxicity to the liver were evaluated using Mito-CTC through discriminating and imaging HClO, indicating that Mito-CTC has the potential function of evaluating the toxicity of the drug to the liver.

This work demonstrates a novel chemosensor, SPTPA, that exhibits fluorescence and colorimetric dual sensing of hypochlorite with an ICT ON strategy. Additionally, the chemosensor successfully detected and imaged endogenous hypochlorite in living cells, various types of bacteria, and zebrafish.