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High molecular weight polyethylenimine (HMW PEI; branched 25 kDa PEI) has been widely investigated for gene delivery due to its high transfection efficiency. However, the toxicity and lack of targeting to specific cells have limited its clinical application. In the present investigation, L-3, 4-dihydroxyphenylalanine (L-DOPA) was conjugated on HMW PEI in order to target L-type amino acid transporter 1 (LAT-1) and modulate positive charge density on the surface of polymer/plasmid complexes (polyplexes). The results of biophysical characterization revealed that the PEI conjugates are able to form nanoparticles ≤ 180 nm with the zeta potential ranging from + 9.5-12.4 mV. These polyplexes could condense plasmid DNA and protect it against nuclease digestion at the carrier to plasmid ratios higher than 4. L-DOPA conjugated PEI derivatives were complexed with a plasmid encoding human interleukin-12 (hIL-12). Targeted polyplexes showed up to 2.5 fold higher transfection efficiency in 4T1 murine mammary cancer cell line, which expresses LAT-1, than 25 kDa PEI polyplexes prepared in the same manner. The cytotoxicity of these polyplexes was also substantially lower than the unmodified parent HMW PEI. These results support the use of L-3, 4-dihydroxyphenylalanine derivatives of PEI in any attempt to develop a LAT-1 targeted gene carrier.

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Cell-free DNA (cfDNA), the DNA in the blood circulation, is a useful marker for diagnosing hereditary diseases and tumors. However, the mechanisms underlying the generation of cfDNA are not completely understood. We previously studied DNases [Caspase-activated DNase (CAD), DNase1L3, and DNase I] and reported that in acetaminophen-induced liver necrosis, DNase1L3 was the main endonuclease generating cfDNA, with CAD playing a supporting role. In this study, we generated triple-gene knockout (TKO) mice, Cad -/-DNase1L3 -/-DNase1 -/-, and found that DNase I also contributed to cfDNA generation. Given that a defect in DNase1L3 or DNase I is involved in autoimmune diseases, TKO mice would be useful as a disease model and tool for identifying the in vivo roles of endonucleases.

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Nuclear factor erythroid 2 (NF-E2)-related factor 3 (NFE2L3), a member of the CNC-bZIP subfamily and widely found in a variety of tissues, is an endoplasmic reticulum (ER) membrane-anchored transcription factor that can be released from the ER and moved into the nucleus to bind the promoter region to regulate a series of target genes involved in antioxidant, inflammatory responses, and cell cycle regulation in response to extracellular or intracellular stress. Recent research, particularly in the past 5 years, has shed light on NFE2L3's participation in diverse biological processes, including cell differentiation, inflammatory responses, lipid homeostasis, immune responses, and tumor growth. Notably, NFE2L3 has been identified as a key player in the development and prognosis of multiple cancers including colorectal cancer, thyroid cancer, breast cancer, hepatocellular carcinoma, gastric cancer, renal cancer, bladder cancer, esophageal squamous cell carcinoma, T cell lymphoblastic lymphoma, pancreatic cancer, and squamous cell carcinoma. Furthermore, research has linked NFE2L3 to other cancers such as lung adenocarcinoma, malignant pleural mesothelioma, ovarian cancer, glioblastoma multiforme, and laryngeal carcinoma, indicating its potential as a target for innovative cancer treatment approaches. Therefore, to gain a better understanding of the role of NFE2L3 in disease, this review offers insights into the discovery, structure, function, and recent advancements in the study of NFE2L3 to lay the groundwork for the development of NFE2L3-targeted cancer therapies.

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Epigenetic alterations critically affect tumor development. Polycomb-group complexes constitute an evolutionarily conserved epigenetic machinery that regulates stem cell fate and development. They are implicated in tumorigenesis, primarily via histone modification. Polycomb repressive complex 1 (PRC1) complexes 1-6 (PRC1.1-6) mediate the ubiquitination of histone H2A on lysine 119 (H2AK119ub). Here, we studied the functional roles of a PRC1.6 molecule, L3MBTL2, in neuroblastoma (NB) cells. L3MBTL2-knockout and knockdown revealed that L3MBTL2 depletion suppressed NB cell proliferation via cell-cycle arrest and gamma-H2A.X upregulation. L3MBTL2-knockout profoundly suppressed xenograft tumor formation. Transcriptome analysis revealed suppressed cell-cycle-related and activated differentiation-related pathways. Break repair meiotic recombinase recruitment factor 1 (BRME1) and nuclear receptor interacting protein 3 (NRIP3) were notably de-repressed by L3MBTL2-knockout. The deletion of L3MBTL2 reduced enrichment of H2AK119ub and PCGF6 at transcriptional start site proximal regions of the targets. Add-back studies unveiled the importance of L3MBTL2-BRME1 and -NRIP3 axes for NB cell proliferation. We further manifested the association of MYCN with de-repression of NRIP3 in an L3MBTL2-deficient context. Therefore, this study first revealed the significance of L3MBTL2-mediated gene silencing in MYCN-amplified NB cells.

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Developing proteins with increased chemical space by expanding the amino acids alphabet has been an emerging technique to compete for the obstacle encountered by their need in various applications. 3,4-Dihydroxyphenylalanine (L-DOPA) catecholic unnatural amino acid is abundantly present in mussels foot proteins through post-translational modification of tyrosine to give a strong adhesion toward wet rocks. L-DOPA forms: bidentate coordination, H-bonding, metal-ligand complexes, long-ranged electrostatic, and van der Waals interactions via a pair of donor hydroxyl groups. Incorporating catechol in proteins through genetic code expansion paved the way for developing: protein-based bio-sensor, implant coating, bio-conjugation, adhesive bio-materials, biocatalyst, metal interaction and nano-biotechnological applications. The increased chemical spaces boost the protein properties by offering a new chemically active interaction ability to the protein. Here, we review the technique employed to develop a genetically expanded organism with catechol to provide novel properties and functionalities; and we highlight the importance of L-DOPA incorporated proteins in biomedical and industrial fields.

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The hypothalamus is a key link in neuroendocrine regulations, which are provided by neuropeptides and dopamine. Until the late 1980 s, it was believed that, along with peptidergic neurons, hypothalamus contained dopaminergic neurons. Over time, it has been shown that besides dopaminergic neurons expressing the dopamine transporter and dopamine-synthesizing enzymes - tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) - the hypothalamus contains neurons expressing only TH, only AADC, both enzymes or only dopamine transporter. The end secretory product of TH neurons is L-3,4-dihydroxyphenylalanine, while that of AADC neurons and bienzymatic neurons lacking the dopamine transporter is dopamine. During ontogenesis, especially in the perinatal period, monoenzymatic neurons predominate in the hypothalamic neuroendocrine centers. It is assumed that L-3,4-dihydroxyphenylalanine and dopamine are released into the neuropil, cerebral ventricles, and blood vessels, participating in the regulation of target cell differentiation in the perinatal period and the functioning of target cells in adulthood.

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Mansonella perstans infections are widespread in Sub-Saharan Africa and Central and South America and thus can be considered as the most prevalent parasite of man in tropical Africa. In contrast to the high prevalence, knowledge about the biology of this filarial nematode is restricted and no effective treatment regimens of this ivermectin-resistant parasite is lacking. An obstacle for the research is that M. perstans resides in body cavities and thus have been only rarely recovered during surgery or autopsy. Therefore, alternative methods like in vitro culture systems need to be implemented to decipher the nature of mansonellosis and effective drugs. Previously, we have established a monkey kidney epithelial cell-based in vitro culture for the maintenance of M. perstans infective larvae (L3) up to 77 days. However, no alternative for this culture system have been postulated to allow longer survival rates and development of adult worms in vitro. Thus, we aim to establish an alternative in vitro culture system for M. perstans L3. M. perstans L3 were isolated from engorged and laboratory reared Culicoides midges. The larvae were then cultured in Dulbecco's Modified Eagle Medium supplemented with either 10% foetal bovine serum (FBS), 10% newborn calf serum (NCS) or 1% bovine serum albumin (BSA) together with human colon carcinoma cells (HCT-8) as feeder cells. Survival and growth were recorded. We obtained that the 10% NCS culture condition was superior allowing long-term maintenance of M. perstans L3 for up to 100 days and boosted growth of the parasites for up to 5-folds compared to the initial size at culture inception. Although no moulting of the L3 into L4 or adult worms could be overserved, the human colon carcinoma cell-based in vitro culture provides an alternative platform to analyse M. perstans biology and screen for novel drugs against M. perstans.

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The normalization of X-ray absorption near-edge structure (XANES) spectra is required for comparing spectral features and extracting quantitative information in analytical techniques such as linear combination analysis, principal component analysis and multivariate curve resolution. Most published data are normalized to the edge-jump, but normalization to the spectral area has also been applied. The latter is particularly attractive if only a small energy range around the absorption can be recorded reliably. Here, the two normalization methods are compared at the L3-edge of Pt, Pd and Rh, and at the Ni K-edge using experimental and calculated spectra. Normalization to the spectral area is found to be a viable approach if the range for the area normalization is sufficiently large.

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This study describes the patterns of dialect use among L3 Norwegian speakers born in Poland who have migrated to Norway. We collected the data in the form of sociolinguistic interviews recorded in Tromsø and Oslo, two different dialect regions, in order to examine potential differences in acquisition of two dissimilar dialects in Norwegian by L3 speakers. The analyses focus on dialectal and accentual variation in their speech, and whether frequency of dialect use is dependent on selected sociocultural factors. We have found that some speakers, especially those scoring high for overall dialect use, also display style-shifting, i.e. they use dialect features from the region more frequently in unscripted speech as opposed to in more formal speech styles elicited through reading tasks or the wordlist reading tasks. This demonstrates that language learners are capable of developing sensitivity towards the vernacular form in an L3. Moreover, it shows that first-generation migrant communities in fact may be capable of developing their L2/L3/L4 language competencies in a similar way to L1 speakers, including at the level of sociolinguistic variation.

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We developed a nondestructive three-dimensional microbial visualization method utilizing synchrotron radiation X-ray microscale computed tomography to better understand the relationship between microorganisms and their surrounding habitats. The method was tested and optimized using a mixture of axenic Escherichia coli and Comamonas testosteroni. The osmium-thiocarbohydrazide-osmium method was used to stain all the microbial cells, and gold in situ hybridization was used to detect specific phylogenetic microbial groups. The stained samples were embedded in epoxy resin for microtomographic analysis. Differences in X-ray absorbances were calculated by subtracting the pre-L3-edge images from the post-L3-edge images to visualize the osmium and gold signals. Although we successfully detected cells stained with osmium, those labeled with gold were not detected, probably because of the insufficient density of gold atoms in the microbial cells. We then applied the developed technique to anaerobic granules and visualized the distribution of microbial cells and extracellular polymeric substances. Empty spaces were highlighted to determine the cavity distribution in granules. Numerous independent cavities of different sizes were identified in the granules. The developed method can be applied to various environmental samples for deeper insights into microbial life in their habitats. IMPORTANCE: Microorganisms inhabit diverse environments and often form biofilms. One factor that affects their community structure is the surrounding physical environment. The arrangement of residential space within the formed biofilm plays a crucial role in the supply and transportation of substances, as well as the discharge of metabolites. Conventional approaches, such as scanning electron microscopy and confocal laser scanning microscopy combined with fluorescence in situ hybridization, have limitations as they provide information primarily from the biofilm surface and cross-sections. In this study, we developed a method for detecting microorganisms in biofilms using synchrotron radiation X-ray microscale computer tomography. The developed method allows nondestructive three-dimensional observation of biofilms at a single-cell resolution (voxel size of approximately 200 nm), facilitating an understanding of the relationship between microorganisms and their physical habitats.

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Benzene is a common environmental pollutant and significant health hazard. Low-dose benzene exposure is common in most industrial settings, and some workers exhibit hematotoxicity characterized by impaired hematopoietic function. Consequently, understanding the early hematopoietic damage and biomarkers associated with low-dose benzene exposure is of critical importance for health risk assessment. Using data from a 5-year prospective cohort study on benzene exposure and the National Center for Biotechnology Information's Gene Expression Omnibus database, we detected significant downregulation of the ubiquitin-conjugating enzyme UBE2L3 (E2) in benzene-exposed subjects compared to control subjects. Liquid chromatography tandem mass spectrometry and co-immunoprecipitation experiments illustrated the binding interaction between UBE2L3 and the ubiquitin-protein ligase ZNF598 (E3). We applied deep learning algorithms to predict candidate interacting proteins and then conducted validation via co-immunoprecipitation experiments, which showed that ZNF598 engages in binding with the autophagy protein LAMP-2. Subsequent overexpression and knockdown of UBE2L3 coupled with immunofluorescence experiments and transmission electron microscopy revealed that UBE2L3 disrupts the ubiquitination-degradation of LAMP-2 by ZNF598, reduces GPX4 expression levels, and activates an autophagy-dependent ferroptosis pathway. It also leads to increased lipid peroxidation, thereby promoting ferroptosis and contributing to the hematotoxicity induced by benzene. In summary, our results suggest that UBE2L3 may be involved in early hematopoietic damage by modulating the autophagy-dependent ferroptosis signaling pathway in benzene-induced hematotoxicity.

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DNASE1L3 is an extracellular nuclease that digests chromatin released from apoptotic cells. DNASE1L3 mutations impair the enzyme function, enhance autoantibody production and type I interferon (IFN-I) responses, and cause different autosomal recessive phenotypes ranging from hypocomplementemic urticarial vasculitis syndrome to full-blown systemic lupus erythematosus (SLE). Kidney involvement in patients with DNASE1L3 mutations is poorly characterised. Herein, we describe the clinical course of three children with monogenic SLE due to DNASE1L3 mutations who developed refractory glomerulonephritis leading to kidney failure. They had different renal histopathological patterns (i.e., membranous, endo- and extra-capillary glomerulonephritis and thrombotic microangiopathy), all belonging to the lupus nephritis (LN) spectrum. One patient had a mixed phenotype, showing an overlap between SLE and ANCA-associated vasculitis. Using immunofluorescence, we detected glomerular expression of the IFN I-induced human myxovirus resistance protein 1 (MXA), which was particularly evident in glomerular endothelial cells. 2/3 patients had increased expression of interferon-stimulated genes in the peripheral blood and all three patients had reduced serum DNAse activity. Our findings suggest that DNASE1L3-related glomerulonephritis can be included in the spectrum of IFN I-mediated kidney disorders, and provide the rationale for IFN I-directed therapies in order to improve the poor outcome of this rare condition.

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Monomethylation of lysine 20 of histone H4 (H4K20me1) is catalyzed by Set8 and thought to play important roles in many aspects of genome function that are mediated by H4K20me binding proteins. We interrogated this model in a developing animal by comparing in parallel the transcriptomes of Set8 null , H4 K20R/A , and l(3)mbt mutant Drosophila melanogaster We found that the gene expression profiles of H4 K20A and H4 K20R larvae are markedly different than Set8 null larvae despite similar reductions in H4K20me1. Set8 null mutant cells have a severely disrupted transcriptome and fail to proliferate in vivo, but these phenotypes are not recapitulated by mutation of H4 K20 , indicating that the developmental defects of Set8 null animals are largely due to H4K20me1-independent effects on gene expression. Furthermore, the H4K20me1 binding protein L(3)mbt is recruited to the transcription start sites of most genes independently of H4K20me even though genes bound by L(3)mbt have high levels of H4K20me1. Moreover, both Set8 and L(3)mbt bind to purified H4K20R nucleosomes in vitro. We conclude that gene expression changes in Set8 null and H4 K20 mutants cannot be explained by loss of H4K20me1 or L(3)mbt binding to chromatin and therefore that H4K20me1 does not play a large role in gene expression.

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Accurate diagnosis of ulcerative colitis (UC) and Crohn's disease (CD), the main subtypes of inflammatory bowel disease (IBD), has been challenging due to the constraints of the current techniques. N6-methyl adenosine (m6A) regulators have evolved as key players in IBD pathogenesis; however, their relation to its clinical setting is largely unexplored. This study investigated the potential of selected RNA methylation machinery and m6A target genes as serum biomarkers of UC and CD, their predictive and discriminating capabilities, and their correlations with laboratory data, interleukin (IL)-6, interferon-γ, disease activity scores, and pathological features. Fifty UC and 45 CD patients, along with 30 healthy volunteers were enlisted. The mRNA expression levels of the m6A writers methyltransferase-like 3 (METTL3) and Wilms-tumor associated protein (WTAP), and the reader YTH domain family, member 1 (YTHDF1), along with the m6A candidate genes sex determining region Y-box 2 (SOX2), hexokinase 2 (HK2), and ubiquitin-conjugating enzyme E2 L3 (UBE2L3) were upregulated in UC patients, whereas only METTL3, HK2, and UBE2L3 were upregulated in CD patients versus controls. Serum WTAP (AUC = 0.94, 95 %CI = 0.874-1.006) and HK2 (AUC = 0.911, 95 %CI = 0.843-0.980) expression levels showed excellent diagnostic accuracy for UC, METTL3 showed excellent diagnostic accuracy for CD (AUC = 0.91, 95 %CI = 0.828-0.992), meanwhile, WTAP showed excellent discriminative power between the two diseases (AUC = 0.91, 95 %CI = 0.849-0.979). Multivariate logistic analysis unveiled the association of METTL3 and UBE2L3 expression with the risk of CD and UC diagnosis, respectively, controlled by age and sex as confounders. Remarkable correlations were recorded between the gene expression of studied m6A regulators and targets in both diseases. Among UC patients, serum METTL3 and WTAP were correlated with UC extent/type, while WTAP was correlated with IL-6. Among CD patients, serum METTL3 and HK2 were correlated with CD activity index (CDAI) and CD location. In conclusion, m6A regulators and target genes are distinctly expressed in UC and CD clinical samples, correlate with disease activity and extent/location, and could serve as a novel approach to empower the diagnosis and stratification of IBD subtypes.

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BACKGROUND: Congenital lumbar facet joint defect is a rare congenital developmental disorder with only a few reported cases in the literature, primarily affecting the L5-S1 segments. This study reports the first case of a defect in the left L3 inferior articular process; and presents a review of the existing literature on the subject, proposes a classification system, and validates the inter-observer and intra-observer reliability of this classification system. CASE PRESENTATION: A 14-year-old boy presented to our orthopedic clinic with persistent lower back pain for 1 month. Imaging analysis, including CT scans, 3D reconstruction, and MRI, revealed a congenital lumbar facet joint defect at the L3 level, which has not been reported. Conservative treatment resulted in a significant improvement in his symptoms, and he is currently under follow-up care. CONCLUSION: Congenital defect of the lumbar facet joint is a rare spinal condition. This article reports the first patient with a defect in the left L3 inferior articular process and conducts a comprehensive literature review, proposing a classification of articular process defects into five types. The two most common types are Types B and C. We have demonstrated that this system is reliable and reproducible and have described the treatment of each type.

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Lethal(3)malignant brain tumor-like protein 2 (L3MBTL2) has been related to transcriptional inhibition and chromatin compaction. Nevertheless, the biological functions and mechanisms of L3MBTL2 are undefined in breast cancer (BRCA). Here, we revealed that L3MBTL2 is responsible for the decline of Nischarin (NISCH), a well-known tumor suppressor, in BRCA, and explored the detailed mechanism. Knockdown of L3MBTL2 reduced monoubiquitination of histone H2A at lysine-119 (H2AK119ub), leading to reduced binding to the NISCH promoter and increased expression of NISCH. Meanwhile, the knockdown of L3MBTL2 decreased proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of BRCA cells, and increased apoptosis, which were abated by NISCH knockdown. Nucleolar transcription factor 1 (UBTF) induced the transcription of L3MBTL2 in BRCA, and the suppressing effects of UBTF silencing on EMT in BRCA cells were also reversed by NISCH knockdown. Knockdown of UBTF slowed tumor progression and attenuated lung tumor infiltration, whereas simultaneous knockdown of NISCH accelerated EMT and increased tumor lung metastasis. Taken together, our results show that L3MBTL2, transcriptionally activated by UBTF, exerts oncogenic functions in BRCA, by catalyzing H2AK119Ub and reducing expression of NISCH.

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BACKGROUND: Breast cancer is the most common malignant tumor, and metastasis remains the major cause of poor prognosis. Glucose metabolic reprogramming is one of the prominent hallmarks in cancer, providing nutrients and energy to support dramatically elevated tumor growth and metastasis. Nevertheless, the potential mechanistic links between glycolysis and breast cancer progression have not been thoroughly elucidated. METHODS: RNA-seq analysis was used to identify glucose metabolism-related circRNAs. The expression of circSIPA1L3 in breast cancer tissues and serum was examined by qRT-PCR, and further assessed its diagnostic value. We also evaluated the prognostic potential of circSIPA1L3 by analyzing a cohort of 238 breast cancer patients. Gain- and loss-of-function experiments, transcriptomic analysis, and molecular biology experiments were conducted to explore the biological function and regulatory mechanism of circSIPA1L3. RESULTS: Using RNA-seq analysis, circSIPA1L3 was identified as the critical mediator responsible for metabolic adaption upon energy stress. Gain- and loss-of-function experiments revealed that circSIPA1L3 exerted a stimulative effect on breast cancer progression and glycolysis, which could also be transported by exosomes and facilitated malignant behaviors among breast cancer cells. Significantly, the elevated lactate secretion caused by circSIPA1L3-mediated glycolysis enhancement promoted the recruitment of tumor associated macrophage and their tumor-promoting roles. Mechanistically, EIF4A3 induced the cyclization and cytoplasmic export of circSIPA1L3, which inhibited ubiquitin-mediated IGF2BP3 degradation through enhancing the UPS7-IGF2BP3 interaction. Furthermore, circSIPA1L3 increased mRNA stability of the lactate export carrier SLC16A1 and the glucose intake enhancer RAB11A through either strengthening their interaction with IGF2BP3 or sponging miR-665, leading to enhanced glycolytic metabolism. Clinically, elevated circSIPA1L3 expression indicated unfavorable prognosis base on the cohort of 238 breast cancer patients. Moreover, circSIPA1L3 was highly expressed in the serum of breast cancer patients and exhibited high diagnostic value for breast cancer patients. CONCLUSIONS: Our study highlights the oncogenic role of circSIPA1L3 through mediating glucose metabolism, which might serve as a promising diagnostic and prognostic biomarker and potential therapeutic target for breast cancer.

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Background The pathological response rate in operable breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC) is postulated to be related to body composition. The success of complete pathological response (pCR) is a known prognostic factor in BC patients treated with NAC. We aimed to accurately measure body composition through BMI and skeletal muscle mass and observe their effects on pCR. Materials and methods Patients diagnosed with operable BC who had a positron emission tomography-computed tomography (PET-CT) or chest/abdominal CT taken at the time of diagnosis were retrospectively screened and enrolled in this study. Muscle mass was defined by third lumbar vertebra (L3) level transverse CT images, and data, including weight and height, were collected from the chemotherapy records. All these data were evaluated together with the postoperative pathological results. Results Sixty-nine operable BC patients with a median age of 46 (range: 29-72) years were included in the study. In all patients, regardless of sarcopenia, 23% (n = 16) achieved pCR to NAC. The pCR rate was 37.5% (n=6) in sarcopenic patients and 62.5% (n=10) in non-sarcopenic patients (p = 0.530). Overweight (n=4; 25%) and obese (n=2; 12.5%) patients also had a lower pathological response than normal-weight (n=10; 62.5%) BC patients (p=0.261). Conclusion Both sarcopenia and obesity independently and synergistically contribute to poorer pathological responses after NAC. Addressing these conditions through tailored interventions, such as nutritional support, exercise programs, and careful monitoring of body composition, could improve treatment outcomes. Further research with larger patient populations and comprehensive body measurements is essential to fully understand these relationships and develop effective strategies to mitigate their impact.

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Post-surgical abdominal adhesions, although poorly understood, are highly prevalent. The molecular processes underlying their formation remain elusive. This review aims to assess the relationship between neutrophil extracellular traps (NETs) and the generation of postoperative peritoneal adhesions and to discuss methods for mitigating peritoneal adhesions. A keyword or medical subject heading (MeSH) search for all original articles and reviews was performed in PubMed and Google Scholar. It included studies assessing peritoneal adhesion reformation after abdominal surgery from 2003 to 2023. After assessing for eligibility, the selected articles were evaluated using the Critical Appraisal Skills Programme checklist for qualitative research. The search yielded 127 full-text articles for assessment of eligibility, of which 7 studies met our criteria and were subjected to a detailed quality review using the Critical Appraisal Skills Programme (CASP) checklist. The selected studies offer a comprehensive analysis of adhesion pathogenesis with a special focus on the role of neutrophil extracellular traps (NETs) in the development of peritoneal adhesions. Current interventional strategies are examined, including the use of mechanical barriers, advances in regenerative medicine, and targeted molecular therapies. In particular, this review emphasizes the potential of NET-targeted interventions as promising strategies to mitigate postoperative adhesion development. Evidence suggests that in addition to their role in innate defense against infections and autoimmune diseases, NETs also play a crucial role in the formation of peritoneal adhesions after surgery. Therefore, therapeutic strategies that target NETs are emerging as significant considerations for researchers. Continued research is vital to fully elucidate the relationship between NETs and post-surgical adhesion formation to develop effective treatments.

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This study was aimed to uncover the character and potential regulatory mechanism of EPB41L3 in cervical cancer (CC). CC cells were injected into BALB/c nude mice (female) to construct a xenograft tumor model. Real-time quantitative polymerase chain reaction (qRT-PCR) and western blot were performed to evaluate the expression of EPB41L3, ERK/p38 MAPK signal markers in CC tissues and cells. Cell counting kit-8 (CCK-8) and Transwell was applied to analyze the viability, invasion, and migration of CC cell lines. EPB41L3 was substantially decreased both in CC tissues and cells. Cell viability, invasion, and migration of CC cells were reduced by overexpressing EPB41L3. Bioinformatics analysis prerdicted that EPB41L3 was strongly related to the ERK/p38 MAPK pathway. Compared with Ad-nc mice, the volume and weight of tumors and ERK/p38 MAPK signal markers were down-regulated in Ad-EPB41L3 mice. After knocking down EPB41L3 with EPB41L3 siRNA (siEPB41L3), the ERK/p38 MAPK pathway was activated. Moreover, SB203580 treatment reversed the effect of EPB41L3 silencing on the improvement in viability, migration, and invasion of CC cells. EPB41L3 suppresses the progression of CC via activating the ERK/p38 MAPK pathway. EPB41L3 may serve as an effective therapeutic target for CC.