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1.
Article in English | MEDLINE | ID: mdl-39017861

ABSTRACT

PURPOSE OF REVIEW: Hip injuries in elite athletes are an increasingly recognized problem and range from chronic overuse injuries, such as adductor strains and labral tears, to acute traumatic injuries such as hip dislocations. In this article, we review common hip pathology experienced by elite athletes and sideline management of emergent hip injuries. RECENT FINDINGS: Elite athletes are subject to unique physical and mental stresses and therefore must be evaluated and treated in a unique manner. Hip and groin injuries account for approximately 6% of sport injuries overall and 3-15% of all injuries in professional sports. Hip sideline emergencies were rare but can include hip dislocations, subluxations, and avulsion fractures. Hip and groin injuries represent an important subset of injuries which can greatly impact an athlete's ability to perform. Understanding the physiology and types of hip/groin injuries, which athletes are prone to injuries, the impact on recovery time, recurrence risk, and the potential need for surgery aid sports medicine physicians in decision-making.

2.
F S Sci ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39025326

ABSTRACT

OBJECTIVE: To study the possible role for HMGA2 overexpression in differentiated myometrial cells and its potential to induce a stem cell-like or dedifferentiating phenotype and drive fibroid development. DESIGN: Myometrial cells were immortalized and transduced with an HMGA2 lentivirus to produce HMGA2hi cells. In vitro stem cell assays were conducted and RNA from HMGA2hi and control cells and fibroid-free myometrial (MyoN) and HMGA2 fibroid (HMGA2F) tissues were submitted for RNA-sequencing. SETTING: University research laboratory SUBJECTS: Women undergoing hysterectomy for symptomatic uterine fibroids or other gynecological conditions. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: In-vitro stem-like properties from myometrium cell lines. RNA-sequencing and collagen production of HMGA2 overexpressing primary leiomyoma tissue and cell lines. RESULTS: HMGA2hi cells have enhanced self-renewal capacity, decreased proliferation, and have a greater ability to differentiate into other mesenchymal cell types. HMGA2hi cells exhibit a stem cell-like signature and share transcriptomic similarities with HMGA2F. Moreover, dysregulated extracellular matrix pathways are observed in both HMGA2hi cells and HMGA2F. CONCLUSION: Our findings suggest that HMGA2 overexpression drives myometrial cells to dedifferentiate into a more plastic phenotype and provides evidence for an alternative mechanism for fibroid etiology, suggesting that fibroids may not only arise from a mutated stem cell but also from a mutated differentiated myometrial cell.

3.
Article in English | MEDLINE | ID: mdl-39004836

ABSTRACT

STUDY DESIGN: Retrospective review of a single institution cohort. OBJECTIVE: To determine whether Area Deprivation Index (ADI) or Social Vulnerability Index (SVI) is more suitable for evaluating minimum clinically important difference (MCID) achievement following elective lumbar fusion as captured by the Patient Reported Outcomes Measurement Information System (PROMIS). SUMMARY OF BACKGROUND DATA: A total of 182 patients who underwent elective one- to two-level posterior lumbar fusion between January 2015 and September 2021. METHODS: ADI and SVI values were calculated from patient-supplied addresses. Patients were grouped into quartiles based on values; higher quartiles represented greater disadvantage. MCID thresholds for Pain Interference (PI) and Physical Function (PF) were determined via a distribution-based method. Multivariable logistic regression was performed to identify factors impacting MCID attainment. Univariate logistic regression was performed to determine which themes comprising SVI values affected MCID achievement. Statistical significance was set at P<0.05. RESULTS: Multivariate logistic regression demonstrated that ADI and SVI quartile assignment significantly impacted achievement of MCID for PI (P=0.04 and P=0.01 respectively) and PF (P=0.03 and P=0.02 respectively). Specifically, assignment to the third ADI and SVI quartiles were significant for PI (OR: 0.39 and 0.23 respectively), and PF (OR: 0.24 and 0.22 respectively). Race was not a significant predictor of MCID for either PI or PF. Univariate logistic regression demonstrated that among SVI themes, the socioeconomic status theme significantly affected achievement of MCID for PI (P=0.01), while the housing type and transportation theme significantly affected achievement of MCID for PF (P=0.01). CONCLUSION: ADI and SVI quartile assignment were predictors of MCID achievement. While ADI and SVI may both identify patients at risk for adverse outcomes following lumbar fusion, SVI offers greater granularity in terms of isolating themes of disadvantage impacting MCID achievement.

4.
Angew Chem Int Ed Engl ; : e202405681, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38985847

ABSTRACT

Photocatalytic hydrogen production offers an alternative pathway to establish a sustainable energy economy. While numerous photoactive materials exhibit potential for generating hydrogen from water, the synergy achieved by combining two different materials with complementary properties in the form of heterojunctions can significantly their photocatalytic activity. Our study describes the design and generation of the metal-organic framework-derived (MOF) metal oxide heterojunction composed of RuO2/N,S-TiO2. The RuO2/N,S-TiO2 is generated through the pyrolysis of MOFs, Ru- HKUST-1, and the amino-functionalized MIL-125-NH2. Among the various RuO2/N,S- TiO2 materials tested, the material characterized by the lowest RuO2 content, exhibited the highest hydrogen evolution rate, producing 10,761 µmol·hr-1·g-1 of hydrogen with an apparent quantum-yield of 10.0% in pure water. In addition to RuO2/N,S-TiO2, we generated two other MOF-derived metal-oxide heterojunctions, ZnO/N,S-TiO2 and In2O3/N,S-TiO2, leading to apparent quantum yields of 0.7% and 0.3%, respectively. The remarkable photocatalytic activity observed in RuO2/N,S-TiO2 is thought to be attributed to the synergistic effects arising from the combination of metallic properties inherent in the metal oxides, their band alignment, porosity, and surface properties inherited from the parent MOFs. The photocatalytic efficiency of RuO2/N,S-TiO2 was further demonstrated in actual water samples, producing hydrogen with a rate of 8,190 µmol·hr-1·g-1 in tap water.

5.
J Chem Phys ; 160(18)2024 May 14.
Article in English | MEDLINE | ID: mdl-38716849

ABSTRACT

Potential applications of previously synthesized pillared graphene oxide frameworks with phenyldiboronic acid linkers in the field of the adsorption and separation of polar protic and aprotic liquid solvents have been systematically explored using grand canonical Monte Carlo simulations. Particular attention was initially paid to the adsorption of pure liquid water, methanol, and dimethyl sulfoxide. The results obtained a significant increase in the isosteric heat of adsorption at low uptake in the case of dimethyl sulfoxide, which is about 17.9 and 26.8 kJ/mol higher than the values corresponding to methanol and water adsorption. These findings indicated that from a thermodynamic point of view, these pillared graphene oxide frameworks could be used in the separation of dimethyl sulfoxide-water liquid mixtures. Systematic grand canonical Monte Carlo simulations were then subsequently performed for dimethyl sulfoxide-water mixtures, with a low dimethyl sulfoxide concentration. The calculated values of the separation selectivity indicate that these materials could have potential applications in the separation of these mixed liquid solvents. Molecular dynamics simulations performed for a representative adsorbed mixture have revealed a substantial slowing down of the dynamics under confinement, particularly in the case of the hydrogen bonds formed between water and dimethyl sulfoxide.

6.
bioRxiv ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38712187

ABSTRACT

Uterine fibroids are prevalent benign tumors in women that exhibit considerable heterogeneity in clinical presentation and molecular characteristics, necessitating a deeper understanding of their etiology and pathogenesis. HMGA2 overexpression has been associated with fibroid development, yet its precise role remains elusive. Mutations in fibroids are mutually exclusive and largely clonal, suggesting that tumors originate from a single mutant cell. We explored a possible role for HMGA2 overexpression in differentiated myometrial cells, hypothesizing its potential to induce a stem cell-like or dedifferentiating phenotype and drive fibroid development. Myometrial cells were immortalized and transduced with an HMGA2 lentivirus to produce HMGA2hi cells. In vitro stem cell assays were conducted and RNA from HMGA2hi and control cells and fibroid-free myometrial and HMGA2 fibroid (HMGA2F) tissues were submitted for RNA-sequencing. HMGA2hi cells have enhanced self-renewal capacity, decreased proliferation, and have a greater ability to differentiate into other mesenchymal cell types. HMGA2hi cells exhibit a stem cell-like signature and share transcriptomic similarities with HMGA2F. Moreover, dysregulated extracellular matrix pathways are observed in both HMGA2hi cells and HMGA2F. Our findings suggest that HMGA2 overexpression drives myometrial cells to dedifferentiate into a more plastic phenotype and underscore a pivotal role for HMGA2 in fibroid pathogenesis.

7.
World Neurosurg ; 187: e107-e114, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38616025

ABSTRACT

OBJECTIVE: To determine how depression state impacts postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores and achievement of minimum clinically important difference (MCID) following lumbar fusion. Depression has been shown to negatively impact outcomes following numerous orthopedic surgeries. Situational and major clinical depression can differentially affect postoperative outcomes. METHODS: Adult patients undergoing elective 1-3 level lumbar fusion were reviewed. Patients with a formal diagnosis of major depression were classified as "clinically depressed" whereas patients with at least "mild" PROMIS Depression scores in the absence of formal depression diagnosis were deemed "situationally depressed." analysis of variance testing was used to assess differences within and between groups. Multivariate regression was used to identify features associated with the achievement of MCID. RESULTS: Two hundred patients were included. The average age was 65.9 ± 12.2 years. 75 patients (37.5%) were nondepressed, 66 patients (33.0%) were clinically depressed, and 59 patients (29.5%) were situationally depressed. Situationally depressed patients had worse preoperative physical function (PF) and pain interference (PI) scores and were more likely to have severe symptoms (P = 0.001, P = 0.001). All groups improved significantly from preoperative baseline scores. All groups met MCID PF at different rates, with highest proportion of situationally depressed reaching this metric (P = 0.03). Rates of achieving MCID PI were not significantly different between groups (P = 0.47). Situational depression was predictive of achieving MCID PF (P = 0.002) but not MCID PI. CONCLUSIONS: Our study investigated the relationship between depression and postoperative PROMIS scores and identified situationally depressed patients as having the worst preoperative impairment. Despite this, the situationally depressed cohort had the highest likelihood of achieving MCID PF, suggestive of a bidirectional relationship between lumbar degenerative disease and subclinical, situational depression. These findings may help guide preoperative counseling on expectations, and patient selection.


Subject(s)
Depression , Elective Surgical Procedures , Lumbar Vertebrae , Recovery of Function , Spinal Fusion , Humans , Spinal Fusion/psychology , Female , Male , Aged , Lumbar Vertebrae/surgery , Middle Aged , Elective Surgical Procedures/psychology , Depression/psychology , Depression/etiology , Patient Reported Outcome Measures , Retrospective Studies , Minimal Clinically Important Difference
8.
In Vivo ; 38(3): 1260-1265, 2024.
Article in English | MEDLINE | ID: mdl-38688602

ABSTRACT

BACKGROUND/AIM: Endometrial cancer (EC) is the predominant malignancy among gynecologic cancers and ranks fourth among all types of cancer. Recently, researchers have focused on the development of new prognostic biomarkers. Subunits of the SWI/SNF protein complex, like the ARID1 and BRG1, have been associated with the development of endometrial cancer. The present study aimed to evaluate the expression patterns of ARID1A and BRG1 in a collection of endometrioid adenocarcinomas of the uterus using immunohistochemistry. PATIENTS AND METHODS: The study comprised a total of thirty-three individuals diagnosed with stage I endometrioid endometrial cancer, treated with radical hysterectomy. The histological material was then examined to assess the cytoplasmic and nuclear expression of the proteins. RESULTS: ARID1A exhibited expression in both the cytoplasm and nucleus of cancer cells, whereas BRG1 was mainly expressed in the nuclei. In addition, ARID1A exhibited a notable decrease in expression in grade 3 histology, with no significant correlation with the depth of myometrial invasion. The reduced expression was highly related to tumor expansion into the endocervix. The findings demonstrated a total absence of ARID1A expression in 27% of endometrioid carcinomas, with a significant reduction in expression in an additional 51% of cancer cells. These findings align with the most recent published data. In contrast, in the current study, BRG1 was rarely down-regulated and was extensively expressed in the majority of endometrioid carcinomas, preventing the possibility of statistical analysis. CONCLUSION: In summary, ARID1A expression loss can be used as a biomarker to guide post-operative therapy; however, further investigation is needed, especially for early-stage endometrial cancer.


Subject(s)
Biomarkers, Tumor , DNA Helicases , DNA-Binding Proteins , Endometrial Neoplasms , Immunohistochemistry , Nuclear Proteins , Transcription Factors , Humans , Female , Endometrial Neoplasms/pathology , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , DNA Helicases/genetics , DNA Helicases/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Middle Aged , Aged , Biomarkers, Tumor/metabolism , Neoplasm Staging , Prognosis , Gene Expression Regulation, Neoplastic , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/metabolism , Carcinoma, Endometrioid/genetics , Adult , Neoplasm Grading
9.
Cancer Diagn Progn ; 4(2): 91-96, 2024.
Article in English | MEDLINE | ID: mdl-38434913

ABSTRACT

Endometrial cancer is a commonly diagnosed gynecological malignancy presenting an increasing incidence worldwide. The immune response plays a crucial role in the mechanisms underlying carcinogenesis and the progression of tumors. In recent times, there has been a discernible surge in the acknowledgment of the importance of programmed death ligand 1 (PDL1) in evading the immunological response of the host and promoting the growth of malignancies. The primary aim of this review is to consolidate the existing corpus of evidence pertaining to the role of PDL1 in the etiology and progression of endometrial cancer and investigate the molecular mechanisms involved in the expression of PDL1 in cells impacted by endometrial cancer. Finally, the association between PDL1 expression and clinical outcomes, as well as the potential therapeutic uses of targeting the PDL1 pathway are being analyzed.

10.
Anticancer Res ; 44(2): 503-510, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38307554

ABSTRACT

BACKGROUND/AIM: Cervical cancer is the fourth most common cause of cancer-related deaths in women worldwide. The potential for targeted therapy against the immune checkpoint programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) and receptor tyrosine kinases was examined in cervical cancer patients and cell lines. MATERIALS AND METHODS: On tissue microarrays, PD-L1 was analyzed in 123 samples of patients with cervical cancer using immunohistochemistry. In SiHa, HeLa, and CaSki cervical cancer cell lines we examined the combination of lenvatinib with a PD-1/PD-L1 inhibitor using cell viability assays, the activation of cell signaling pathway proteins using western blots and gene expression using quantitative reverse transcriptase-PCR. RESULTS: Of 113 evaluable samples, 90 (79.6%) had more than 1% PD-L1 positive cells. The single treatment with the PD-1/PD-L1 inhibitor resulted in the greatest reduction in growth for CaSki and lenvatinib in HeLa cells. In contrast, the combined treatment of lenvatinib with the PD-1/PD-L1 inhibitor demonstrated a significantly stronger impeded proliferation compared to the single treatment in all three cell lines. Moreover, the combined treatment caused significantly less phosphorylation of the signaling molecules ERK and S6 in SiHa and of S6 and STAT3 in HeLa cells but not in CaSki. All treatments diminished the mRNA levels of PD-L1, Il-8, and FGFR in SiHa cells. CONCLUSION: PD1 is frequently expressed in cervical cancer samples. Combining lenvatinib with a PD-1/PD-L1 inhibitor diminished proliferation of cervical cancer cell lines. Consequently, this combination might be a promising option to treat cervical cancer. Signaling pathways involved in tumor cell growth are blocked by the combined treatment but still a model of the underlying mechanism cannot be drawn.


Subject(s)
Immune Checkpoint Inhibitors , Phenylurea Compounds , Quinolines , Uterine Cervical Neoplasms , Female , Humans , B7-H1 Antigen/metabolism , HeLa Cells , Immune Checkpoint Inhibitors/therapeutic use , Prevalence , Programmed Cell Death 1 Receptor , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/genetics
11.
Chempluschem ; 89(5): e202300634, 2024 May.
Article in English | MEDLINE | ID: mdl-38183391

ABSTRACT

Prompted by the need for related analytical reference material in the frame of the fight against doping in sports, synthetic efforts towards the main long-term bishydroxylated metabolite (LGD-LTM1) of the nonsteroidal selective androgen receptor modulator (SARM) ligandrol have produced related derivatives that were exploited for a targeted metabolite analysis of urine samples obtained in the course of previous excretion studies of this SARM. Further clarifying ligandrol's metabolic profile, the availability of synthetic reference material permitted the structural elucidation of a previously reported pyrrolidinone-type metabolite and revealed its potential analytical utility as an additional long-term marker. Moreover, synthetic reference material enabled the comparison and validation of liquid chromatography coupled with mass spectrometry (LC-MS)-based and gas chromatography coupled with mass spectrometry (GC-MS)-based detection and identification methods focusing on the LGD-LTM1 marker.


Subject(s)
Gas Chromatography-Mass Spectrometry , Humans , Chromatography, Liquid/methods , Doping in Sports/prevention & control , Pyrrolidinones/chemistry , Pyrrolidinones/metabolism
12.
Spine (Phila Pa 1976) ; 49(9): 601-608, 2024 May 01.
Article in English | MEDLINE | ID: mdl-37163645

ABSTRACT

STUDY DESIGN: Retrospective review of a single institution cohort. OBJECTIVE: The goal of this study is to identify features that predict delayed achievement of minimum clinically important difference (MCID) following elective lumbar spine fusion using Patient-Reported Outcomes Measurement Information System (PROMIS) surveys. SUMMARY OF BACKGROUND DATA: Preoperative prediction of delayed recovery following lumbar spine fusion surgery is challenging. While many studies have examined factors impacting the achievement of MCID for patient-reported outcomes in similar cohorts, few studies have assessed predictors of early functional improvement. METHODS: We retrospectively reviewed patients undergoing elective one-level posterior lumbar fusion for degenerative pathology. Patients were subdivided into two groups based on achievement of MCID for each respective PROMIS domain either before six months ("early responders") or after six months ("late responders") following surgical intervention. Multivariable logistic regression analysis was used to determine features associated with odds of achieving distribution-based MCID before or after six months follow up. RESULTS: 147 patients were included. The average age was 64.3±13.0 years. At final follow-up, 57.1% of patients attained MCID for PI and 72.8% for PF. However, 42 patients (49.4%) reached MCID for PI by six months, compared to 44 patients (41.1%) for PF. Patients with severe symptoms had the highest probability of attaining MCID for PI (OR 10.3; P =0.001) and PF (OR 10.4; P =0.001) Preoperative PROMIS symptomology did not predict early achievement of MCID for PI or PF. Patients who received concomitant iliac crest autograft during their lumbar fusion had increased odds of achieving MCID for PI (OR 8.56; P =0.001) before six months. CONCLUSION: Our study demonstrated that the majority of patients achieved MCID following elective one-level lumbar spine fusion at long-term follow-up, although less than half achieved this clinical benchmark for each PROMIS metric by six months. We also found that preoperative impairment was not associated with when patients would achieve MCID. Further prospective investigations are warranted to characterize the trajectory of clinical improvement and identify the risk factors associated with poor outcomes more accurately.


Subject(s)
Patient Reported Outcome Measures , Humans , Middle Aged , Aged , Treatment Outcome , Retrospective Studies
13.
Spine J ; 24(1): 107-117, 2024 01.
Article in English | MEDLINE | ID: mdl-37683769

ABSTRACT

BACKGROUND CONTEXT: Socioeconomic status (SES) has been associated with differential healthcare outcomes and may be proxied using the area-deprivation index (ADI). Few studies to date have investigated the role of ADI on patient-reported outcomes and clinically meaningful improvement following lumbar spine fusion surgery. PURPOSE: The purpose of this study is to investigate the role of SES on lumbar fusion outcomes using Patient-Reported Outcomes Measurement Information System (PROMIS) surveys. STUDY DESIGN/SETTING: Retrospective review of a single institution cohort. PATIENT SAMPLE: About 205 patients who underwent elective one-to-three level posterior lumbar spine fusion. OUTCOME MEASURES: Change in PROMIS scores and achievement of minimum clinically important difference (MCID). METHODS: Patients 18 years or older undergoing elective one-to-three level lumbar spine fusion secondary to spinal degeneration from January 2015 to September 2021 with minimum one year follow-up were reviewed. ADI was calculated using patient-supplied addresses and patients were grouped into quartiles. Higher ADI values represent worse deprivation. Minimum clinically important difference (MCID) thresholds were calculated using distribution-based methods. Analysis of variance testing was used to assess differences within and between the quartile cohorts. Multivariable regression was used to identify features associated with the achievement of MCID. RESULTS: About 205 patients met inclusion and exclusion criteria. The average age of our cohort was 66±12 years. The average time to final follow-up was 23±8 months (range 12-36 months). No differences were observed between preoperative baseline scores amongst the four quartiles. All ADI cohorts showed significant improvement for pain interference (PI) at final follow-up (p<.05), with patients who had the lowest socioeconomic status having the lowest absolute improvement from preoperative baseline physical function (PF) and PI (p=.01). Only those patients who were in the lowest socioeconomic quartile failed to significantly improve for PF at final follow-up (p=.19). There was a significant negative correlation between socioeconomic level and the absolute proportion of patients reaching MCID for PI (p=.04) and PF (p=.03). However, while ADI was a significant predictor of achieving MCID for PI (p=.02), it was nonsignificant for achieving MCID for PF. CONCLUSIONS: Our study investigated the influence of ADI on postoperative PROMIS scores and identified a negative correlation between ADI quartile and the proportion of patients reaching MCID. Patients in the worse ADI quartile had lower chances of reaching clinically meaningful improvement in PI. Policies focused on alleviating geographical deprivation may augment clinical outcomes following lumbar surgery.


Subject(s)
Socioeconomic Disparities in Health , Spinal Diseases , Humans , Middle Aged , Aged , Spinal Diseases/surgery , Retrospective Studies , Neurosurgical Procedures , Patient Reported Outcome Measures , Treatment Outcome
14.
Plant Foods Hum Nutr ; 78(4): 698-703, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37919537

ABSTRACT

Dietary prebiotic fibers play an important role in modulating gut microbiota by enhancing the abundance of beneficial microorganisms and their bioactive metabolites. However, dietary fibers are a structurally heterogeneous class of polysaccharides, varying in molar mass, branching patterns, and monosaccharide composition, which could influence their utilization by various gut microorganisms. The present study aimed to investigate the effects of molar mass and chemical structure of wheat arabinoxylan fiber (AX) on the growth and metabolism of two key gut resident bacteria (Faecalibacterium prausnitzii and Lacticaseibacillus rhamnosus LGG), which are linked to human health. For this purpose, low, medium, and high molar masses of AX (LAX, MAX, and HAX, respectively) were modified with specific α-arabinofuranosidases to leave only singly substituted, only doubly substituted, or unsubstituted xylose units. Almost all the modified AX samples showed a better prebiotic score than unmodified AX for different molar masses. The modified LAX exhibited a better prebiotic effect than HAX and MAX. In addition, LAX, with doubly substituted xylose units, exhibited the highest prebiotic potential and SCFA production by both microorganisms. Furthermore, AX, either singly or doubly substituted, had a consistent impact on L. rhamnosus growth, whereas AX, with all arabinose residues removed, had a greater impact on F. prausnitzii. These findings support the potential of bioengineered AX as next-generation prebiotics targeting health-related gut microbes.


Subject(s)
Gastrointestinal Microbiome , Prebiotics , Humans , Prebiotics/microbiology , Triticum/chemistry , Xylose , Dietary Fiber/analysis , Xylans/chemistry
15.
Cancers (Basel) ; 15(18)2023 Sep 08.
Article in English | MEDLINE | ID: mdl-37760437

ABSTRACT

Ovarian cancer is a deadly disease that affects thousands of women worldwide. Integrins, transmembrane receptors that mediate cell adhesion and signaling, play important roles in ovarian cancer progression, metastasis, and drug resistance. Dysregulated expression of integrins is implicated in various cellular processes, such as cell migration, invasion, and proliferation. Emerging evidence suggests that microRNAs (miRNAs) can regulate integrin expression and function, thus affecting various physiological and pathological processes, including ovarian cancer. In this article, we review the current understanding of integrin-mediated cellular processes in ovarian cancer and the roles of miRNAs in regulating integrins. We also discuss the therapeutic potential of targeting miRNAs that regulate integrins for the treatment of ovarian cancer. Targeting miRNAs that regulate integrins or downstream signaling pathways of integrins may provide novel therapeutic strategies for inhibiting integrin-mediated ovarian cancer progression.

16.
J Pers Med ; 13(9)2023 Sep 21.
Article in English | MEDLINE | ID: mdl-37763185

ABSTRACT

Bladder malignancy represents the fourth most common cancer in men and the eighth in women in the western world. Women under 75 years of age have a risk of 0.5-1% of developing bladder cancer. The diagnosis usually occurs between 65 and 70 years of age, whereas the mortality rate for women varies from 0.5 to 4 per 100,000 every year. Nulliparous women present a greater risk than women who have given birth. The risk is further decreased when parity increases. Theoretically, hormonal changes occurring during pregnancy play a protective role. Smoking and occupational exposure to specific chemicals are the most common risk factors of bladder cancer. Other risk factors such as chronic urinary tract inflammation, cyclophosphamide, radiotherapy, and familial correlation have been reported. The aim of this review is to highlight a rare combination, which is the co-existence of bladder malignancy and pregnancy. We present thirteen different cases of women who were diagnosed with malignant bladder tumors during their pregnancy. A review of the literature was conducted, focusing on the unspecific symptoms, possible diagnostic tools, and suitable treatment modalities. The management of bladder cancer in pregnancy is a challenging process. The fragile balance between the possible complications of pregnancy and maternal health is yet to be discussed.

17.
Article in English | MEDLINE | ID: mdl-37646968

ABSTRACT

In this study, we aimed to develop a protective probiotic coculture to inhibit the growth of Salmonella enterica serovar Typhimurium in the simulated chicken gut environment. Bacterial strains were isolated from the digestive mucosa of broilers and screened in vitro against Salmonella Typhimurium ATCC 14028. A biocompatibility coculture test was performed, which identified two biocompatible strains, Ligilactobacillus salivarius UO.C109 and Ligilactobacillus saerimneri UO.C121 with high inhibitory activity against Salmonella. The cell-free supernatant (CFS) of the selected isolates exhibited dose-dependent effects, and the inhibitory agents were confirmed to be proteinaceous by enzymatic and thermal treatments. Proteome and genome analyses revealed the presence of known bacteriocins in the CFS of L. salivarius UO.C109, but unknown for L. saerimneri UO.C121. The addition of these selected probiotic candidates altered the bacterial community structure, increased the diversity of the chicken gut microbiota challenged with Salmonella, and significantly reduced the abundances of Enterobacteriaceae, Parasutterlla, Phascolarctobacterium, Enterococcus, and Megamonas. It also modulated microbiome production of short-chain fatty acids (SCFAs) with increased levels of acetic and propionic acids after 12 and 24 h of incubation compared to the microbiome challenged with S. Typhimurium. Furthermore, the selected probiotic candidates reduced the adhesion and invasion of Salmonella to Caco-2 cells by 37-39% and 51%, respectively, after 3 h of incubation, compared to the control. These results suggest that the developed coculture probiotic strains has protective activity and could be an effective strategy to control Salmonella infections in poultry.

18.
Placenta ; 142: 1-11, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37579594

ABSTRACT

INTRODUCTION: Maternal prenatal psychological stress is associated with adverse pregnancy outcomes and increased risk of adverse health outcomes in children. While the molecular mechanisms that govern these associations has not been fully teased apart, stress-induced changes in placental function can drive sex-specific phenotypes in offspring. We sought to identify and examine molecular pathways in the placenta that are altered in response to maternal prenatal stress. METHODS: We previously employed a mouse model of maternal prenatal stress where pregnant dams were treated with stress hormone (CORT) beginning in mid-gestation. Using this model, we conducted RNAseq analysis of whole placenta at E18.5. We used qRT-PCR to validate gene expression changes in the placenta and in a trophoblast cell line. ELISAs were used to measure the abundance of thyroid hormones in maternal and fetal serum and in the placenta. RESULTS: Dio2 was amongst the top differentially expressed genes in response to exogenous stress hormone. Dio2 expression was more downregulated in placenta of female fetuses from CORT-treated dams than both control placenta from females and placenta from male fetuses. Consistent with Dio2's role in production of bioactive thyroid hormone (T3), we found that there was a reduction of T3 in placenta and serum of female embryos from CORT-treated dams at E18.5. Both T3 and T4 were reduced in the fetal compartment of the placenta of female fetuses from CORT-treated dams at E16.5. Exogenous stress hormone induced reduction in thyroid hormone in females was independent of circulating levels of TH in the dams. DISCUSSION: The placental thyroid hormone synthesis pathway may be a target of elevated maternal stress hormone and modulate fetal programming of health and disease of offspring in a sex-specific fashion.


Subject(s)
Corticosterone , Placenta , Humans , Child , Pregnancy , Female , Male , Mice , Animals , Placenta/metabolism , Corticosterone/pharmacology , Corticosterone/metabolism , Thyroid Hormones , Fetus/metabolism , Thyroid Gland
19.
bioRxiv ; 2023 Aug 10.
Article in English | MEDLINE | ID: mdl-37461599

ABSTRACT

Introduction: Maternal prenatal stress is associated with adverse pregnancy outcomes and predisposition to long-term adverse health outcomes in children. While the molecular mechanisms that govern these associations has not been fully teased apart, stress-induced changes in placental function can drive sex-specific phenotypes in offspring. We sought to identify and examine molecular pathways in the placenta that are altered in response to maternal prenatal stress. Methods: Using a mouse model of maternal prenatal stress, we conducted RNA-seq analysis of whole placenta at E18.5. We used qRT-PCR to validate gene expression changes in the placenta and in a trophoblast cell line. ELISAs were used to measure the abundance of thyroid hormones in maternal and fetal serum and in the placenta. Results: Dio2 was amongst the top differentially expressed genes in response to elevated maternal stress hormone. Dio2 expression was more downregulated in female placenta from stressed dams than both female control and male placenta. Consistent with Dio2's role in production of bioactive thyroid hormone (T3), we found that there was a reduction of T3 in placenta and serum of female embryos from stressed dams at E18.5. Both T3 and T4 were reduced in the fetal compartment of the female placenta from stressed dams at E16.5. Stress hormone induced reduction in thyroid hormone in females was independent of circulating levels of TH in the dams. Discussion: The placental thyroid hormone synthesis pathway may be a target of maternal stress and modulate fetal programming of health and disease of offspring in a sex-specific fashion.

20.
Commun Biol ; 6(1): 686, 2023 07 03.
Article in English | MEDLINE | ID: mdl-37400623

ABSTRACT

Myometrial stem/progenitor cells (MyoSPCs) have been proposed as the cells of origin for uterine fibroids, but the identity of the MyoSPC has not been well established. We previously identified SUSD2 as a possible MyoSPC marker, but the relatively poor enrichment in stem cell characteristics of SUSD2+ over SUSD2- cells compelled us to find better markers. We combined bulk RNA-seq of SUSD2+/- cells with single cell RNA-seq to identify markers for MyoSPCs. We observed seven distinct cell clusters within the myometrium, with the vascular myocyte cluster most highly enriched for MyoSPC characteristics and markers. CRIP1 expression was found highly upregulated by both techniques and was used as a marker to sort CRIP1+/PECAM1- cells that were both enriched for colony forming potential and able to differentiate into mesenchymal lineages, suggesting that CRIP1+/PECAM1- cells could be used to better study the etiology of uterine fibroids.


Subject(s)
Leiomyoma , Myometrium , Female , Humans , Myometrium/metabolism , Cysteine/metabolism , Stem Cells/metabolism , Leiomyoma/genetics , Leiomyoma/metabolism
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