(±)-hypermonanones A-G, seven pairs of monoterpenoid polyprenylated acylphloroglucinol enantiomers from Hypericum monanthemum.

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1-7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2H-pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1-7. Compounds (-)-2 and (+)-2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC50 values of 7.07 ± 1.02 µM and 11.39 ± 0.24 µM, respectively.

Genome-wide analysis of two different regions of brain reveals the molecular changes of fertility related genes in rln3a-/- mutants in male Nile tilapia (Oreochromis niloticus).

Relaxin3 (rln3) has been associated with various emotional and cognitive processes, including stress, anxiety, learning, memory, motivational behavior, and circadian rhythm. Notably, previous report revealed that Rln3a played an indispensable role in testicular development and male fertility in Nile tilapia (Oreochromis niloticus). However, the underlying molecular mechanisms remain largely unknown. We found that Rln3a is expressed exclusively in the diencephalon* (Di*) of the brain. Deficiency of Rln3a resulted in a significant increase in serum dopamine level and an upregulation of gene expression of gnrh1 and kisspeptin2. To further elucidate the role of Rln3a in fish fertility, we collected two different regions of Di* and hypothalamus (Hyp) tissues for subsequent RNA-seq analysis of both wild-type (rln3a+/+) and rln3a-/- male tilapia. Upon the transcriptomic data, 1136 and 755 differentially expressed genes (DEGs) were identified in the Di* and Hyp tissues, respectively. In Di*, the up-regulated genes were enriched in circadian rhythm, chemical carcinogenesis, while the down-regulated genes were enriched in type II diabetes mellitus, dopaminergic synapse, and other pathways. In Hyp, the up-regulated genes were enriched in circadian rhythm, pyrimidine metabolism, while the down-regulated genes were enriched in type I diabetes mellitus, autoimmune thyroid disease, and other pathways. Subsequently, the results of both qRT-PCR and FISH assays highlighted a pronounced up-regulation of core circadian rhythm genes, cry1b and per3, whereas genes such as clocka, clockb, and arntl exhibited down-regulation. Furthermore, the genes associated with dopamine biosynthesis were significantly increased in the Hyp. In summary, the mutation of rln3a in male tilapia resulted in notable changes in circadian rhythm and disease-linked signaling pathways in the Di* and Hyp. These changes might account for the fertility defects observed in rln3a-/- male mutants in tilapia.

Multivalent dendritic DNA aptamer molecules for the enhancement of therapeutic effects.

Dendritic DNA molecules, referred to as DNA dendrons, consist of multiple covalently linked strands and are expected to improve the cellular uptake and potency of therapeutic oligonucleotides because of their multivalency. In this study, we developed an efficient synthetic method for producing DNA dendrons using strain-promoted azide-alkyne cycloaddition. Integration of the antitumor aptamer AS1411 into DNA dendrons enhanced cellular uptake and antiproliferative activity in cancer cells. These findings demonstrate that the incorporation of multivalent aptamers into DNA dendrons can effectively boost their therapeutic effects.

Impact of Serious Games on Body Composition, Physical Activity, and Dietary Change in Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Over the past four decades, obesity in children of all ages has increased worldwide, which has intensified the search for innovative intervention strategies. Serious games, a youth-friendly form of intervention designed with educational or behavioral goals, are emerging as a potential solution to this health challenge. To analyze the effectiveness of serious games in improving body composition, physical activity, and dietary change, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) from PubMed, Web of Science, EMBASE, and Scopus databases. Pooled standardized mean differences (SMD) were calculated for 20 studies (n = 2238 the intervention group; n = 1983 in the control group) using random-effect models. The intervention group demonstrated a slightly better, although non-significant, body composition score, with a pooled SMD of -0.26 (95% CI: -0.61 to 0.09). The pooled effect tends to be stronger with longer duration of intervention (-0.40 [95% CI: -0.96, 0.16] for >3 months vs. -0.02 [95% CI: -0.33, 0.30] for ≤3 months), although the difference was not statistically significant (p-difference = 0.24). As for the specific pathways leading to better weight control, improvements in dietary habits due to serious game interventions were not significant, while a direct positive effect of serious games on increasing physical activity was observed (pooled SMD = 0.61 [95% CI: 0.04 to 1.19]). While the impact of serious game interventions on body composition and dietary changes is limited, their effectiveness in increasing physical activity is notable. Serious games show potential as tools for overweight/obesity control among children and adolescents but may require longer intervention to sustain its effect.

[Cannabinoid receptor 1 agonist arachidonyl-2'-chloroethylamide (ACEA) improves sepsis-associated encephalopathy by inhibiting inflammatory factors].

Objective To investigate the impact of the cannabinoid receptor agonist arachidonyl-2'-chloroethylamide (ACEA) on cognitive function in mice with sepsis-associated encephalopathy (SAE). Methods C57BL/6 mice were randomly divided into artificial cerebrospinal fluid (ACSF) and lipopolysaccharide (LPS) groups. The SAE model was established by intraventricular injection of LPS. The severity of sepsis in mice was assessed by sepsis severity score (MSS) and body mass changes. Behavioral paradigms were used to evaluate motor ability (open field test) and cognitive function (contextual fear conditioning test, Y-maze test). To evaluate the effects of ACEA intervention on SAE, mice were randomly assigned to ACSF group, ACEA intervention combined with ACSF group, LPS group, and ACEA intervention combined with LPS group. The dosage of ACEA intervention was 1.5 mg/kg. Real-time quantitative PCR was used to measure the mRNA expression levels of interleukin 1ß (IL-1ß), IL-6, and tumor necrosis factor α (TNF-α) in mouse hippocampal tissues. Western blot analysis was used to assess the protein levels of IL-6 and TNF-α in the hippocampus. Nissl staining was performed to examine neuronal damage in the CA1 region of the mouse hippocampus. Behavioral paradigms were again employed to evaluate motor ability and cognitive function. Results Three days after intraventricular LPS injection, mice exhibited significant cognitive dysfunction, confirming SAE modeling. Compared to the control group, the LPS group showed significant increases in mRNA of inflammatory factors such as IL-6, TNF-α, and IL-1ß, together with significant increases in IL-6 and TNF-α protein levels in the hippocampus, a decrease in Nissl bodies in the CA1 region, and significant cognitive dysfunction. Compared to the LPS group, the ACEA intervention group showed a significant decrease in the mRNA of IL-6, TNF-α, and IL-1ß, a significant reduction in IL-6 and TNF-α protein levels, an increase in Nissl bodies, and improved cognitive function. Conclusion ACEA improves cognitive function in SAE mice by inhibiting the expression levels of inflammatory factors IL-6 and TNF-α.

Comparison of the mesodermal differentiation potential between embryonic stem cells and scalable induced pluripotent stem cells.

BACKGROUND: Mesenchymal stem cells (MSCs) have promising potential in clinical application, whereas their limited amount and sources hinder their bioavailability. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have become prominent options in regenerative medicine as both possess the ability to differentiate into MSCs. METHODS: Recently, our research team has successfully developed human leukocyte antigen (HLA)-homozygous iPSC cell lines with high immune compatibility, covering 13.5% of the Taiwanese population. As we deepen our understanding of the differences between these ESCs and HLA-homozygous iPSCs, our study focused on morphological observations and flow cytometry analysis of specific surface marker proteins during the differentiation of ESCs and iPSCs into MSCs. RESULTS: The results showed no significant differences between the two pluripotent stem cells, and both of them demonstrated the equivalent ability to further differentiate into adipose, cartilage, and bone cells. CONCLUSION: Our research revealed that these iPSCs with high immune compatibility exhibit the same differentiation potential as ESCs, enhancing the future applicability of highly immune-compatible iPSCs.

N6-methyladenosine facilitates mitochondrial fusion of colorectal cancer cells via induction of GSH synthesis and stabilization of OPA1 mRNA.

Mitochondria undergo fission and fusion that are critical for cell survival and cancer development, while the regulatory factors for mitochondrial dynamics remain elusive. Herein we found that RNA m6A accelerated mitochondria fusion of colorectal cancer (CRC) cells. Metabolomics analysis and function studies indicated that m6A triggered the generation of glutathione (GSH) via the upregulation of RRM2B-a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential. This in turn resulted in the mitochondria fusion of CRC cells. Mechanistically, m6A methylation of A1240 at 3'UTR of RRM2B increased its mRNA stability via binding with IGF2BP2. Similarly, m6A methylation of A2212 at the coding sequence (CDS) of OPA1-an essential GTPase protein for mitochondrial inner membrane fusion-also increased mRNA stability and triggered mitochondria fusion. Targeting m6A through the methyltransferase inhibitor STM2457 or the dm6ACRISPR system significantly suppressed mitochondria fusion. In vivo and clinical data confirmed the positive roles of the m6A/mitochondrial dynamics in tumor growth and CRC progression. Collectively, m6A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression, which facilitated cancer cell growth and CRC development.

METTL3 promotes cellular senescence of colorectal cancer via modulation of CDKN2B transcription and mRNA stability.

Cellular senescence plays a critical role in cancer development, but the underlying mechanisms remain poorly understood. Our recent study uncovered that replicative senescent colorectal cancer (CRC) cells exhibit increased levels of mRNA N6-methyladenosine (m6A) and methyltransferase METTL3. Knockdown of METTL3 can restore the senescence-associated secretory phenotype (SASP) of CRC cells. Our findings, which were confirmed by m6A-sequencing and functional studies, demonstrate that the cyclin-dependent kinase inhibitor 2B (CDKN2B, encoding p15INK4B) is a mediator of METTL3-regulated CRC senescence. Specifically, m6A modification at position A413 in the coding sequence (CDS) of CDKN2B positively regulates its mRNA stability by recruiting IGF2BP3 and preventing binding with the CCR4-NOT complex. Moreover, increased METTL3 methylates and stabilizes the mRNA of E2F1, which binds to the -208 to -198 regions of the CDKN2B promoter to facilitate transcription. Inhibition of METTL3 or specifically targeting CDKN2B methylation can suppress CRC senescence. Finally, the METTL3/CDKN2B axis-induced senescence can facilitate M2 macrophage polarization and is correlated with aging and CRC progression. The involvement of METTL3/CDKN2B in cell senescence provides a new potential therapeutic target for CRC treatment and expands our understanding of mRNA methylation's role in cellular senescence.

Brucine Inhibits Proliferation of Pancreatic Ductal Adenocarcinoma through PI3K/AKT Pathway-induced Mitochondrial Apoptosis.

INTRODUCTION: The purpose of this research was to settle the role of brucine in pancreatic ductal adenocarcinoma (PDAC) and the mechanisms involved. METHODS: The findings of this study suggest that brucine exerts inhibitory effects on cell growth, clonogenicity, and invasive potential of Panc02 and Mia Paca-2 cells. These effects may be linked to an increase in apoptotic-prone cell population. RESULTS: Gene sequencing data suggests that these effects are mediated through the induction of apoptosis. Experimental evidence further supports the notion that brucine reduces mitochondrial membrane potential and upregulates Bax expression while downregulating Bcl-2 expression. These effects are believed to be a result of brucine-mediated suppression of PI3K/Akt activity, which serves as a regulatory factor of mTOR, Bax, and Bcl-2. Suppression of PI3K activity enhances the tumor-suppressing effects of brucine. CONCLUSION: Overall, these findings suggest that brucine has therapeutic potential as a remedy option for PDAC.

Dysregulation of the circRNA_0087207/miR-548c-3p/PLSR1-TGFB2 axis in Leber hereditary optic neuropathy in vitro.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is mainly the degeneration of retinal ganglion cells (RGCs) associated with high apoptosis and reactive oxygen species (ROS) levels, which is accepted to be caused by the mutations in the subunits of complex I of the mitochondrial electron transport chain. The treatment is still infant while efforts of correcting genes or using antioxidants do not bring good and consistent results. Unaffected carrier carries LHON mutation but shows normal phenotype, suggesting that the disease's pathogenesis is complex, in which secondary factors exist and cooperate with the primary complex I dysfunction. METHODS: Using LHON patient-specific induced pluripotent stem cells (iPSCs) as the in vitro disease model, we previously demonstrated that circRNA_0087207 had the most significantly higher expression level in the LHON patient-iPSC-derived RGCs compared with the unaffected carrier-iPSC-derived RGCs. To elaborate the underlying pathologies regulated by circRNA_008720 mechanistically, bioinformatics analysis was conducted and elucidated that circRNA_0087207 could act as a sponge of miR-548c-3p and modulate PLSCR1/TGFB2 levels in ND4 mutation-carrying LHON patient-iPSC-derived RGCs. RESULTS: Using LHON iPSC-derived RGCs as the disease-based platform, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on targeted mRNA of miR-548c-3p showed the connection with apoptosis, suggesting downregulation of miR548c-3p contributes to the apoptosis of LHON patient RGCs. CONCLUSION: We showed that the downregulation of miR548c-3p plays a critical role in modulating cellular dysfunction and the apoptotic program of RGCs in LHON.

Safety of nighttime elective hepatectomy for hepatocellular carcinoma patients: a retrospective study.

Purpose: This study aimed to investigate whether nighttime elective surgery influenced the short-term outcomes and prognosis of hepatocellular carcinoma (HCC) patients. Methods: The 1,339 HCC patients who underwent hepatectomy were divided into the daytime surgery group (8 a.m.-6 p.m., n = 1,105) and the nighttime surgery group (after 6 p.m., n = 234) based on the start time of surgery. The 1:2 propensity score matching (PSM) analysis was used to control confounding factors. The short-term outcomes of HCC patients in the 2 groups were compared before and after PSM. Factors associated with major complications (Clavien-Dindo grade, ≥III) and textbook oncologic outcomes (TOO) were separately identified by multivariable logistic regression based on variables screened via least absolute shrinkage and selection operator (LASSO). The Kaplan-Meier method was used to analyze overall survival (OS) and recurrence-free survival (RFS). Results: TOO was achieved after surgery in 897 HCC patients. HCC patients in the nighttime surgery group had a higher body mass index (P = 0.010). After 1:2 PSM, the baseline characteristics of patients between the 2 groups were similar. Short-term outcomes in HCC patients were comparable both before and after PSM (all Ps > 0.05), as were TOO in the 2 groups before (P = 0.673) and after PSM (P = 0.333). In our LASSO-logistic regression, nighttime surgery was not an independent factor associated with major complications or TOO. Both groups also had similar OS (P = 0.950) and RFS (P = 0.740) after PSM. Conclusion: Our study revealed the safety of nighttime elective hepatectomy for HCC patients.

A multiple cancer cell optical biosensing metastructure realized by CPA.

A one-dimensional optical biosensing metastructure (OBM) with graphene layers is presented in this paper. It is realized by coherent perfect absorption (CPA) and operates in the transverse electric mode. It shows a strong linear fitting relationship between the refractive index (RI) of the analysis layer and the frequency corresponding to the absorption peak, and the R-square is up to 1. Additionally, based on the principle of CPA, the OBM can realize the function of multiple cancer cell detection by adjusting the detection range by controlling the phase difference of coherent electromagnetic waves. Its detection ranges are 1.34-1.355 and 1.658-1.662. Thanks to its high-quality factor, great figure of merit, and low detection limit, whose best values are, respectively, 6.9 × 104, 1.2 × 104 RIU-1, and 3.6 × 10-6 RIU, the detection of weak changes in the RI of a cancer cell is possible. Additionally, its sensitivity can reach 26.57 THz RIU-1. This OBM based on CPA has major implications for advancing the study and investigation into the application of CPA. It also provides a simple and efficient approach to distinguish cancer cells and may be widely used in the biomedical field.

New perspectives on cancer clinical research in the era of big data and machine learning.

In the 21st century, the development of medical science has entered the era of big data, and machine learning has become an essential tool for mining medical big data. The establishment of the SEER database has provided a wealth of epidemiological data for cancer clinical research, and the number of studies based on SEER and machine learning has been growing in recent years. This article reviews recent research based on SEER and machine learning and finds that the current focus of such studies is primarily on the development and validation of models using machine learning algorithms, with the main directions being lymph node metastasis prediction, distant metastasis prediction, and prognosis-related research. Compared to traditional models, machine learning algorithms have the advantage of stronger adaptability, but also suffer from disadvantages such as overfitting and poor interpretability, which need to be weighed in practical applications. At present, machine learning algorithms, as the foundation of artificial intelligence, have just begun to emerge in the field of cancer clinical research. The future development of oncology will enter a more precise era of cancer research, characterized by larger data, higher dimensions, and more frequent information exchange. Machine learning is bound to shine brightly in this field.

Lifetime dairy product consumption and breast cancer risk: a prospective cohort study by tumor subtypes.

BACKGROUND: Previous literature on dairy products and risk of breast cancer is inconsistent, and the relationship may depend on the life-period of dietary assessment. OBJECTIVE: We examined dairy consumption from adolescence through later adulthood and incidence of breast cancer by menopausal status and tumor molecular subtypes in the Nurses' Health Study (NHS), a prospective cohort study. METHODS: We analyzed data from 63,847 females in the NHS collected from 1980 to 2018. Average intake of dairy products during adulthood was assessed by validated semiquantitative food frequency questionnaires throughout follow-up. Participants recalled adolescent dietary intake in 1986. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) relating dairy product consumption to breast cancer risk overall, by menopausal status, and by subtypes. RESULTS: We documented 5733 incident cases of invasive breast cancer during 32 y of follow-up (n = 5298 postmenopausal). Lifetime, adolescent, adulthood, and postmenopausal total dairy and milk intakes were not associated with overall breast cancer risk (nonsignificant HRs comparing highest with lowest quintile range = 0.97-1.08), although there was a suggestive positive association between adolescent milk intake and breast cancer risk (HR: 1.09; 95% CI: 1.00, 1.18). Higher lifetime and premenopausal cheese intakes were associated with modestly lower risks of breast cancer (comparing highest with lowest quintile, HR for lifetime cheese intake: 0.90; 95% CI: 0.82, 0.98; HR for premenopausal cheese intake: 0.89; 95% CI: 0.79, 1.00). Results varied by tumor subtype and some evidence for heterogeneity was observed for an association between premenopausal milk intake and breast cancer (HR for estrogen receptor [ER]-positive: 0.84; 95% CI: 0.72, 0.99; ER-negative: 1.36; 95% CI: 1.00, 1.84; P heterogeneity = 0.04). CONCLUSIONS: These findings suggest that overall dairy consumption was not associated with risk of breast cancer. However, heterogeneity was observed for type of dairy food, period of life, and tumor subtypes.

IL-10+CD19+ regulatory B cells induce CD4+Foxp3+regulatory T cells in serum of cervical cancer patients.

Increase of regulatory T cells (Tregs) in the tumour microenvironment predicts worse survival of patients with various types of cancer. Recently, B cells play a significant role in the maintenance of Treg cells. However, the relevance of regulatory B cells (Bregs) to tumour immunity in humans remains elusive. Flow cytometry analysis was used to detect the Bregs and Tregs. Double staining results illustrated that the proportion of Bregs and Tregs were prominently higher in cervical cancer than normal tissues. Increase of Bregs and Tregs in cervical cancer microenvironment was associated with poor survival. Furthermore, Bregs cocultured with cervical cancer cell lines increased and induced Tregs. To sum up, the increased expression of Bregs contributes to the differentiation of CD4+ T cells into Tregs in the cervical cancer.

Brucea Javanica Oil Emulsion Injection inhibits proliferation of pancreatic cancer via regulating apoptosis-related genes.

Brucea Javanica Oil Emulsion Injection (BJOEI) has been proven to have extensive anti-tumor effects. But the anti-cancer mechanisms need further exploration. So, the aim of this study was to investigate the role and mechanisms of BJOEI on pancreatic cancer using network pharmacology and experimental validation. Disease targets were obtained from the GSE101448 dataset in the Gene Expression Omnibus (GEO) database. Eight active ingredients were identified following a comprehensive literature search. The target genes of BJOEI were obtained from the SwissTarget Prediction database. The core targets of BJOEI and the involved signaling pathways were determined using the compound-target network, protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. GO and KEGG enrichment analyses of 50 potential overlapping genes indicated that BJOEI exerted therapeutic effects on pancreatic cancer through the apoptotic pathway. In vitro experiments further revealed that BJOEI could suppress cell growth and invasion, arrest cells at the S stage, and cause cell apoptosis in three pancreatic cell lines. Additionally, BJOEI inhibited tumor growth in vivo. Among the 15 key genes regulating apoptosis, 11 were upregulated, while 4 were downregulated. PPARG emerged as a core target in bioinformatics analysis. The ability of PPARG to regulate apoptosis was validated by Western Blot. Our findings verified that BJOEI could regulate apoptosis-related genes, especially PPARG, thereby inducing apoptosis and inhibiting proliferation in pancreatic cancer cells. BJOEI can impede pancreatic cancer progression and induce cell apoptosis. The underlying mechanism appears to be closely associated with the regulation of apoptosis-related genes.

PIVKA-II combined with tumor burden score to predict long-term outcomes of AFP-negative hepatocellular carcinoma patients after liver resection.

BACKGROUND: This study aimed to establish a simple prognostic scoring model based on tumor burden score (TBS) and PIVKA-II to predict long-term outcomes of α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) patients. METHODS: 511 patients were divided into the training cohort (n = 305) and the validation cohort (n = 206) at a ratio of 6:4. Receiver operating characteristic curves (ROC) were established to identify cutoff values of TBS and PIVKA-II. Kaplan-Meier curves were used to analyze survival outcomes. The multivariable Cox regression was used to identify variables independently associated with survival outcomes. The predictive performance of the TBS-PIVKA II score (TPS) model was compared with Barcelona clinic liver cancer (BCLC) stage and American Joint Committee on Cancer (AJCC TNM) stage. RESULTS: The present study established the TPS model using a simple scoring system (0, 1 for low/high TBS [cutoff value: 4.1]; 0, 1 for low/high PIVKA-II [cutoff value: 239 mAU/mL]). The TPS scoring model was divided into three levels according to the summation of TBS score and PIVKA-II score: TPS 0, TPS 1, and TPS 2. The TPS scoring model was able to stratify OS (training: p < 0.001, validation: p < 0.001) and early recurrence (training: p < 0.001; validation: p = 0.001) in the training cohort and the validation cohort. The TPS score was independently associated with OS (TPS 1 vs. 0, HR: 2.28, 95% CI: 1.01-5.17; TPS 2 vs. 0, HR: 4.21, 95% CI: 2.01-8.84) and early recurrence (TPS 1 vs. 0, HR: 3.50, 95% CI: 1.71-7.16; TPS 2 vs. 0, HR: 3.79, 95% CI: 1.86-7.75) in the training cohort. The TPS scoring model outperformed BCLC stage and AJCC TNM stage in predicting OS and early recurrence in the training cohort and the validation cohort. But the TPS scoring model was unable to stratify the late recurrence in the training cohort (p = 0.872) and the validation cohort (p = 0.458). CONCLUSIONS: The TPS model outperformed the BCLC stage and AJCC TNM stage in predicting OS and early recurrence of AFP-negative HCC patients after liver resection, which might better assist surgeons in screening AFP-negative HCC patients who may benefit from liver resection.

ICT-based fluorescent probes for intracellular pH and biological species detection.

Fluorescent probes, typically based on the intramolecular charge transfer (ICT) mechanism, have received considerable research attention in cell detection due to their non-invasiveness, fast response, easy regulation, high sensitivity, and low damage tolerance for in vivo bio-samples. Generally, intracellular pH and biological species such as various gases, metal ions, and anions constitute the foundation of cells and participate in the basic physiological processes, whose abnormal level can lead to poisoning, cardiovascular disease, and cancer in living organisms. Therefore, monitoring of their quantity plays an essential role in understanding the status of organisms and preventing, diagnosing, and treating diseases. In the last decades, remarkable progress has been made in developing ICT probes for the detection of biological elements. In this review, we highlight the recent ICT probes focusing primarily on the detection of intracellular pH, various gases (H2S, CO, H2O2, and NO), metal ions (Cu2+, Hg2+, Pb2+, Zn2+, and Al3+), and anions (ClO-, CN-, SO3 2-, and F-). In addition, we discuss the issues and limitations of ICT-based fluorescent probes for in vivo detection and explore the clinical translational potential and challenges of these materials, providing valuable guidance and insights for the design of fluorescent materials.

HLA-Homozygous iPSC-Derived Mesenchymal Stem Cells Rescue Rotenone-Induced Experimental Leber's Hereditary Optic Neuropathy-like Models In Vitro and In Vivo.

BACKGROUND: Mesenchymal stem cells (MSCs) hold promise for cell-based therapy, yet the sourcing, quality, and invasive methods of MSCs impede their mass production and quality control. Induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) can be infinitely expanded, providing advantages over conventional MSCs in terms of meeting unmet clinical demands. METHODS: The potential of MSC therapy for Leber's hereditary optic neuropathy (LHON) remains uncertain. In this study, we used HLA-homozygous induced pluripotent stem cells to generate iMSCs using a defined protocol, and we examined their therapeutic potential in rotenone-induced LHON-like models in vitro and in vivo. RESULTS: The iMSCs did not cause any tumorigenic incidence or inflammation-related lesions after intravitreal transplantation, and they remained viable for at least nine days in the mouse recipient's eyes. In addition, iMSCs exhibited significant efficacy in safeguarding retinal ganglion cells (RGCs) from rotenone-induced cytotoxicity in vitro, and they ameliorated CGL+IPL layer thinning and RGC loss in vivo. Optical coherence tomography (OCT) and an electroretinogram demonstrated that iMSCs not only prevented RGC loss and impairments to the retinal architecture, but they also improved retinal electrophysiology performance. CONCLUSION: The generation of iMSCs via the HLA homozygosity of iPSCs offers a compelling avenue for overcoming the current limitations of MSC-based therapies. The results underscore the potential of iMSCs when addressing retinal disorders, and they highlight their clinical significance, offering renewed hope for individuals affected by LHON and other inherited retinal conditions.

Expression profiles of human somatic mesenchymal stem cells derived from fresh endometrium, ectopic-endometrium and umbilical cord.

OBJECTIVES: The study investigated the stem cell expression profiles and differentiation capacities of mesenchymal stem cells (MSCs) from different tissues, specifically human eutopic endometrium MSCs (eut-MSCs), ectopic endometrium MSCs (ect-MSCs), and umbilical cord MSCs (UC-MSCs). Our aim was to identify any similarities in subpopulations among these MSCs and lay a foundation for MSCs repair. MATERIAL AND METHODS: MSCs were isolated from endometrial tissue (n = 5), endometriosis tissue (n = 6), and umbilical cords (n = 7). Flow cytometry was used to examine cell phenotype, and three lineage tests were conducted to evaluate the differentiation capacity of the MSCs. RESULTS: Eut-MSCs expressed CD44 (98.00 ± 0.96%), CD73 (99.54 ± 0.02%), CD140b (99.16 ± 0.50%), CD146 (93.87 ± 2.27%), SUSD2 (50.76 ± 8.15%), and CD271 (2.1 ± 1.22%). Ect-MSCs expressed CD44 (98.23 ± 1.60%), CD73 (99.63 ± 0.04%), CD140b (98.13 ± 0.53%), CD146 (93.88 ± 3.19%), SUSD2 (49.33 ± 6.36%), and CD271 (2.85 ± 1.17%). UC-MSCs expressed CD44 (99.11 ± ± 0.42%), CD73 (99.65 ± 0.12%), CD140b (99.84 ± 0.42%), CD146 (88.09 ± 4.20%), SUSD2 (72.87 ± 7.13%), and CD271 (6.19 ± 2.08%). The expression of SUSD2 and CD271 in UC-MSCs was slightly but not significantly higher than that in ect-MSCs and eut-MSCs. However, CD44, CD73, CD140b, and CD146 showed similar expression levels in UC-MSCs, ect-MSCs, and eut-MSCs. All three types of MSCs demonstrated the capacity to differentiate into osteoblasts, adipocytes, and chondrocytes. CONCLUSIONS: Our findings indicate that ect-MSCs, eut-MSCs, and UC-MSCs have similar stem cell phenotypes and the ability to differentiate into three lineages.