Cervical Glands Research Articles

Personalized Management of Malignant and Non-Malignant Ectopic Mediastinal Thyroid: A Proposed 10-Item Algorithm Approach.

We aimed to analyze the management of the ectopic mediastinal thyroid (EMT) with respect to EMT-related cancer and non-malignant findings related to the pathological report, clinical presentation, imaging traits, endocrine profile, connective tissue to the cervical (eutopic) thyroid gland, biopsy or fine needle aspiration (FNA) results, surgical techniques and post-operatory outcome. This was a comprehensive review based on revising any type of freely PubMed-accessible English, full-length original papers including the keywords "ectopic thyroid" and "mediastinum" from inception until March 2024. We included 89 original articles that specified EMTs data. We classified them into four main groups: (I) studies/case series (n = 10; N = 36 EMT patients); (II) malignant EMTs (N = 22 subjects; except for one newborn with immature teratoma in the EMT, only adults were reported; mean age of 62.94 years; ranges: 34 to 90 years; female to male ratio of 0.9). Histological analysis in adults showed the following: papillary (N = 11/21); follicular variant of the papillary type (N = 2/21); Hürthle cell thyroid follicular malignancy (N = 1/21); poorly differentiated (N = 1/21); anaplastic (N = 2/21); medullary (N = 1/21); lymphoma (N = 2/21); and MALT (mucosa-associated lymphoid tissue) (N = 1/21); (III) benign EMTs with no thyroid anomalies (N = 37 subjects; mean age of 56.32 years; ranges: 30 to 80 years; female to male ratio of 1.8); (IV) benign EMTs with thyroid anomalies (N = 23; female to male ratio of 5.6; average age of 52.1 years). This panel involved clinical/subclinical hypothyroidism (iatrogenic, congenital, thyroiditis-induced, and transitory type upon EMT removal); thyrotoxicosis (including autonomous activity in EMTs that suppressed eutopic gland); autoimmune thyroiditis/Graves's disease; nodules/multinodular goiter and cancer in eutopic thyroid or prior thyroidectomy (before EMT detection). We propose a 10-item algorithm that might help navigate through the EMT domain. To conclude, across this focused-sample analysis (to our knowledge, the largest of its kind) of EMTs, the EMT clinical index of suspicion remains low; a higher rate of cancer is reported than prior data (18.8%), incident imagery-based detection was found in 10-14% of the EMTs; surgery offered an overall good outcome. A wide range of imagery, biopsy/FNA and surgical procedures is part of an otherwise complex personalized management.

Assessing the multifaceted cervix: examining cervical gland area at cervical length screening to predict spontaneous preterm birth

BACKGROUNDBiologically active cervical glands provide a mucous barrier while influencing the composition and biomechanical strength of the cervical extracellular matrix. Cervical remodeling during ripening may be reflected as loss of the sonographic cervical gland area. As sonographic cervical length remains suboptimal for universal screening, adjunctive evaluation of other facets of the mid-trimester cervix may impart additional screening benefit. OBJECTIVETo sonographically assess the cervical gland area at universal cervical length screening for preterm birth. STUDY DESIGNWe performed a retrospective cohort study of singletons with transvaginal cervical length screening universally performed during anatomic survey between 18 0/7 and 23 6/7 weeks and subsequent live delivery at a single institution in 2018. Uterine anomalies, cerclage, suboptimal imaging, or medically indicated preterm birth were excluded. Ultrasound images were assessed for cervical length and cervical gland area (with quantitative measurements when present). The primary outcome was spontaneous preterm birth <37 weeks. Absent and present gland groups were compared using χ2, Fisher's exact, T-test, and multivariate logistic regression (adjusting for parity and progesterone use, as well as the gestational age, cervical length, and gland absence at screening ultrasound). Gland measurements were evaluated using the Mann-Whitney-U Test and Spearman's correlation. RESULTSAmong the cohort of 772 patients, absent and present CGA groups were overall similar. Patients were on average 33 years old, ∼20 weeks gestation at screening ultrasound, and overall, 2.5% had history of prior spontaneous preterm birth. The absent gland group was more likely to have been taking progesterone (17% vs 4%, P=.04). Overall rate of preterm birth was 2.6%. However, the 2.3% of patients with absent cervical gland area were significantly more likely to deliver <37 weeks (aOR 23.9, 95% CI 6.4–89, P<.001). Multivariate logistic regression demonstrated better performance of a cervical length screening model for preterm birth prediction with the addition of qualitative gland evaluation (P<.001). Qualitative gland assessment was reproducible (PABAK 0.89), but quantitative gland measurements did not correlate with preterm birth. CONCLUSIONQualitative gland absence at mid-gestation cervical length screening was associated with subsequent spontaneous preterm birth, whereas quantitative gland measurements were not. Multifaceted ultrasound screening may be needed to adequately evaluate the multiple biologic functions of the cervix.

Knowledge and Practice Regarding Abnormal Vaginal Discharge Among Adolescent Females in Riyadh City: An Observational Study.

Introduction Vaginal discharge (VD) is a common condition that affects women during their childbearing years and often requires medical attention. It results from the physiological secretion of cervical and Bartholin's glands, as well as the shedding of vaginal epithelial cells caused by bacterial action in the vagina, which alters the acidic environment of the vagina.Experiencing vaginal symptoms is a common reason for seeking medical attention, especially among women during their reproductive years. This often leads to a visit to an obstetrician or a gynecologist. Accordingly,addressing such issues becomes even more crucial. The aim of this study is to assess the knowledge and practice regarding abnormal VD (AVD) among adolescent females in Riyadh City, Saudi Arabia. Methods The present study utilized a correlational cross-sectional survey methodology conducted in Riyadh City. The questionnaire was employed as thedata collection instrument from November 2022 to November 2023. Eligibility for inclusion was limited to adolescent femalesand students living in Riyadh City, aged from 14 to 20 years. Electronic consent was obtained from participants aged 18 years and above, while consent from guardians was sought for those below 18 years. This sample size was determined with a minimum requirement of 500 participants, and 824 were involved. The questionnaire encompassed several sections, including demographic characteristics (gender, age, education, and menstruation history), history of AVD, knowledge regarding VD, and students' practices and behaviors related to VD. Cronbach's alpha values for all the sections were more than 0.7. Data analysis was performed using statistical software, employing descriptive analysis, chi-square tests, and t-tests. Results A total of 824 girls were included, and their ages ranged from 14 to 20 years, with a mean age of (16 years ± 5) years old. Exactly 697 (84.6%) were high school students. Most of the study students (85.1%; 701) complained of an AVD at any point in their lives. Only 97 (11.8%) of the study students had a good knowledge level of VD. Higher age, marriage, late menarche, and seeking medical care for complaints of VD were the factors associated with a high knowledge level about VD (P<0.05). Additionally, 44.2% of school-age females sought medical care when experiencing AVD, with reasons including worsening symptoms over time and fear of serious diseases. However, a significant portion of participants opted for self-treatment using herbal remedies, medication from pharmacies, or leaving VD untreated, citing reasons such as perceiving it as a simple condition or fearing examination and disclosure. Conclusion In summary, the current study revealed that adolescent femalesdemonstrate a sub-optimal level of knowledge regarding AVD. These findings are primarily observed among adolescent girls and individuals who exhibit a reluctance to seek appropriate medical intervention when having AVD.

Hyposecretion of cervical MUC5B is related to preterm birth in pregnant women after cervical excisional surgery.

Excisional surgery for cervical intraepithelial neoplasia is a risk factor for preterm birth in subsequent pregnancies. However, the underlying mechanisms of this association remain unclear. We previously showed that cervical MUC5B, a mucin protein, may be a barrier to ascending pathogens during pregnancy. We thus hypothesized that hyposecretion of cervical MUC5B is associated with preterm birth after cervical excisional surgery. This prospective nested case-control study (Study 1) included pregnant women who had previously undergone cervical excisional surgery across 11 hospitals. We used proteomics to compare cervicovaginal fluid at 18-22weeks of gestation between the preterm and term birth groups. In another case-control analysis (Study 2), we compared MUC5B expression in nonpregnant uterine tissues between 15 women with a history of cervical excisional surgery and 26 women without a history of cervical surgery. The abundance of MUC5B in cervicovaginal fluid was significantly decreased in the preterm birth group (fold change=0.41, p=.035). Among the 480 quantified proteins, MUC5B had the second highest positive correlation with gestational age at delivery in the combined preterm and term groups. The cervicovaginal microbiome composition was not significantly different between the two groups. Cervical length was not correlated with gestational age at delivery (r=0.18, p=.079). Histologically, the MUC5B-positive area in the nonpregnant cervix was significantly decreased in women with a history of cervical excisional surgery (0.85-fold, p=.048). The distribution of MUC5B-positive areas in the cervical tissues of 26 women without a history of cervical excisional surgery differed across individuals. This study suggests that the primary mechanism by which cervical excisional surgery causes preterm birth is the hyposecretion of MUC5B due to loss of the cervical glands.

Dual-Energy CT Iodine Uptake of Head and Neck: Definition of Reference Values in a Big Data Cohort.

Despite a considerable amount of literature on dual-energy CT (DECT) iodine uptake of the head and neck, the physiologic iodine uptake of this region has not been defined yet. This study aims to establish reference values for the iodine uptake of healthy organs to facilitate clinical application. Consecutive venous DECT scans of the head and neck were reviewed, and unremarkable exams were included (n = 617). A total of 35 region of interest measurements were performed in 16 anatomical regions. Iodine uptake was compared among different organs/tissues and subgroup analysis was performed (male (n = 403) vs. female (n = 214); young (n = 207) vs. middle-aged (n = 206) vs. old (n = 204); and normal weight (n = 314) vs. overweight (n = 196) vs. obese (n = 107)). Overall mean iodine uptake values ranged between 0.5 and 9.4 mg/mL. Women showed higher iodine concentrations in the cervical vessels and higher uptake for the parotid gland, masseter muscle, submandibular glands, sublingual glands, palatine tonsils, tongue body, thyroid gland, and the sternocleidomastoid muscle than men (p ≤ 0.04). With increasing age, intravascular iodine concentrations increased as well as iodine uptake for cerebellum and thyroid gland, while values for the tongue and palatine tonsils were lower compared to younger subjects (p ≤ 0.03). Iodine concentrations for parotid glands and sternocleidomastoid muscles decreased with a higher BMI (p ≤ 0.004), while normal-weighted patients showed higher iodine values inside the jugular veins, other cervical glands, and tonsils versus patients with a higher BMI (p ≤ 0.04). physiologic iodine uptake values of cervical organs and tissues show gender-, age-, and BMI-related differences, which should be considered in the clinical routine of head and neck DECT.

Utility of UV Signature Mutations in the Diagnostic Assessment of Metastatic Head and Neck Carcinomas of Unknown Primary.

Metastatic carcinoma of unknown primary origin to the head and neck lymph nodes (HNCUP) engenders unique diagnostic considerations. In many cases, the detection of a high-risk human papillomavirus (HR-HPV) unearths an occult oropharyngeal squamous cell carcinoma (SCC). In metastatic HR-HPV-independent carcinomas, other primary sites should be considered, including cutaneous malignancies that can mimic HR-HPV-associated SCC. In this context, ultraviolet (UV) signature mutations, defined as ≥ 60% C→T substitutions with ≥ 5% CC→TT substitutions at dipyrimidine sites, identified in tumors arising on sun exposed areas, are an attractive and underused tool in the setting of metastatic HNCUP. A retrospective review of institutional records focused on cases of HR-HPV negative HNCUP was conducted. All cases were subjected to next generation sequencing analysis to assess UV signature mutations. We identified 14HR-HPV negative metastatic HNCUP to either the cervical or parotid gland lymph nodes, of which, 11 (11/14, 79%) had UV signature mutations, including 4 (4/10, 40%) p16 positive cases. All UV signature mutation positive cases had at least one significant TP53 mutation and greater than 20 unique gene mutations. The management of metastatic cutaneous carcinomas significantly differs from other HNCUP especially metastatic HR-HPV-associated SCC; therefore, the observation of a high percentage of C→T with CC →TT substitutions should be routinely incorporated in next generation sequencing reports of HNCUP. UV mutational signatures testing is a robust diagnostic tool that can be utilized in daily clinical practice.

Mapping Spatiotemporal Heterogeneity in Multifocal Breast Tumor Progression by Noninvasive Ultrasound Elastography-Guided Mass Spectrometry Imaging Strategy.

Spatiotemporal heterogeneity of tumors provides an escape mechanism for breast cancer cells, which can obstruct the investigation of tumor progression. While molecular profiling obtained from mass spectrometry imaging (MSI) is rich in biochemical information, it lacks the capacity for in vivo analysis. Ultrasound diagnosis has a high diagnostic accuracy but low chemical specificity. Here, we describe a noninvasive ultrasound elastography (UE)-guided MSI strategy (UEg-MSI) that integrates physical and biochemical characteristics of tumors acquired from both in vivo and in vitro imaging. Using UEg-MSI, both elasticity histopathology metabolism "fingerprints" and reciprocal crosstalk are revealed, indicating the intact, multifocal spatiotemporal heterogeneity of spontaneous tumorigenesis of the breast from early, middle, and late stages. Our results demonstrate a gradual increase in malignant degree of primary focus in cervical and thoracic mammary glands. This progression is characterized by increased stiffness according to elasticity scores, histopathological changes from hyperplasia to increased nests of neoplastic cells and necrotic areas, and regional metabolic heterogeneity and reprogramming at the spatiotemporal level. De novo fatty acid (FA) synthesis focused on independent (such as ω-9 FAs) and dependent (such as ω-6 FAs) dietary FA intake in the core cancerous nest areas in the middle and late stages of tumor or in the peripheral microareas in the early stage of the tumor. SM-Cer signaling pathway and GPs biosynthesis and degradation, as well as glycerophosphoinositol intensity, changed in multiple characteristic microareas. The UEg-MSI strategy holds the potential to expand MSI applications and enhance ultrasound-mediated cancer diagnosis. It offers new insight into early cancer discovery and the occurrence of metastasis.

Cervical angle as a possible predictor of abnormal placental position in women with endometriosis.

We aimed to examine the effects of endometriosis on the rate of abnormal placentation by comparing the data of pregnant women with and without endometriosis. A case-control study was conducted to compare the perinatal outcomes between women with and without endometriosis. In the subgroup analysis, magnetic resonance imaging (MRI) scans of pregnant women with placenta previa were used to measure the cervical angle and its relationship with endometriosis. The cervical angle was measured as the angle between the cervical glands and the line perpendicular to the spinal column in each sagittal MRI section. We retrospectively analyzed data from 3453 cases of singleton deliveries between 2015 and 2019 at two study facilities. Among them, 159 had clinically or surgically confirmed endometriosis. The odds ratio (OR) for abnormal placental position was significantly higher in pregnant women with endometriosis (OR. 2.82; 95% confidence interval [CI], 1.58-5.04). The OR was 3.21 (95% CI, 1.57-6.55) in the endometriosis-surgery group (91 patients) and 2.32 (95% CI, 0.91-5.88) in the non-surgery group (68 patients). Furthermore, 44 women who underwent pelvic MRI after 30 weeks of gestation were included to examine the cervical angle. Then, we compared the date of pregnant women with (n = 6) and without endometriosis (n = 38). Regardless of placental attachment position, the cervical angle was significantly lower in the group with than in the group without a history of endometriosis. Pregnant women with a history of endometriosis may have stronger uterine retroversion, which could potentially contribute to abnormal placental positioning.

RET/PTC rearrangement in papillary thyroid carcinoma arising in malignant struma ovarii with abdominal wall metastasis and cervical thyroid gland: a case report and review of the literature

BackgroundStruma ovarii refers to rare mature cystic teratomas containing at least 50% of thyroid tissue, and malignant transformation is known to be even rarer. The synchronous development of malignant struma ovarii and cervical thyroid carcinoma are also scarce and poorly understood due to limited data about molecular features. Here, we present the first report of RET/PTC 1 rearrangement in synchronous metastatic malignant struma ovarii to the abdominal wall and cervical thyroid cancer.Case presentationWe described a 47-year-old multigravida woman with bilateral adnexal and lower abdominal wall masses detected during the evaluation of abnormal uterine bleeding. The patient underwent a hysterectomy, bilateral salpingo-oophorectomy, and surgical removal of abdominal wall mass. Then, the pathological evaluation revealed papillary thyroid carcinoma (PTC) within struma ovarii and metastatic PTC in the abdominal wall fibro adipose tissue. Further, cervical thyroid gland physical examination and ultrasound illustrated a nodule within the left lobe. Subsequently, a total thyroidectomy was performed, and a histological examination revealed PTC. Furthermore, all affected tissue, i.e., struma ovarii, abdominal wall metastasis, and cervical thyroid gland tested for BRAF and RAS mutations and RET/PTC 1 rearrangement. RET/PTC 1 rearrangement was identified among all three different sites. Finally, after six years of follow-up, the patient had no evidence of recurrence or distant metastasis.ConclusionsIn light of these findings, malignant struma ovarii might yield a clue to cervical thyroid carcinoma, and the molecular analysis could provide valuable information for understanding the underlying mechanism, tumor clinicopathological behaviors, and prognosis.

Uterine Neurotrophic Tyrosine Receptor Kinase Rearranged Spindle Cell Neoplasms: Three Cases of an Emerging Entity.

Uterine sarcomas are rare; most are either smooth muscle or endometrial stromal in origin. Recent molecular advances have identified several, genetically defined entities with specific morphologic, clinicopathological associations, and therapeutic options. We report 3 cases of uterine neurotrophic tyrosine receptor kinase ( NTRK )-rearranged spindle cell neoplasms," currently classified as "emerging entities" in the WHO Classification of Female Genital Tract Tumors, 2020, Fifth Edition. The affected patients were 32, 34, and 42 years of age. Two patients presented with vaginal bleeding; the third presented with a cervical mass found incidentally during laparoscopy for an ectopic gestation. All 3 tumors were polypoid masses that distorted the cervix. Microscopically, they comprised cellular, fascicular, and storiform, plump spindle cells, with occasional rounded cells, and frequent mitoses (4-48/10 high power fields) in a myxoid stroma. All 3 cases showed entrapment of benign cervical glands. Inflammatory cell infiltrates, including plasma cells, were noted in all 3 tumors. One case had tumor cell necrosis, osteoid-like material, and osteoclast-like giant cells and showed lymphovascular invasion. Immunohistochemically, our cases showed patchy S100 (2/3) and CD34 (3/3) positivity. CD10 was positive in 2/3 cases. 3/3 cases showed pan-tropomyosin receptor kinase positivity (cytoplasmic). The NTRK -translocations demonstrated were: NTRK1::TMP3, NTRK1::TPR, and NTRK3::SPECC1L . Two of the patients had extensive disease and underwent chemotherapy. Larotrectinib was approved for one patient who demonstrated a striking reduction in tumor volume upon initiation of this treatment.

Neonatal Single-Stage Surgical Management of Complicated Distal Vaginal Atresia: Revisiting an Appropriate and Feasible Technique

Hydrometrocolpos is distension of the vagina and uterus with fluid other than pus or blood. It is due to distal vaginal obstruction, and one of its possible causes is agenesis of the distal vagina. Patients with distal vaginal atresia may present in the neonatal period due to stimulation of uterine and cervical glands by maternal estrogen. In this study, we presented our results in managing neonates with complicated hydrometrocolpos due to distal vaginal atresia through a single-stage abdomino-perineal pull-through vaginoplasty. During the period from July 2003 to June 2018, neonates presented to the Department of Pediatric Surgery, Faculty of Medicine, Ain Shams University with complicated hydrometrocolpos (complicated with obstructive uropathy, intestinal obstruction, urinary tract infection, or systemic sepsis) due to distal vaginal atresia were included in the study. All the patients underwent single-stage abdomino-perineal pull-through vaginoplasty with drainage of the accumulated fluid. The patients were followed up for re-accumulation of fluid or vaginal stenosis for at least 4 years after the procedure. During the specified period, 14 neonates with complicated hydrometrocolpos due to distal vaginal atresia (complicated with obstructive uropathy, intestinal obstruction, urinary tract infection, or systemic sepsis) presented to the Department of Pediatric Surgery, Faculty of Medicine, Ain Shams University and underwent single-stage abdomino-perineal pull-through vaginoplasty with drainage of the accumulated fluid. Their age ranged between 4 and 18 days (mean 10, median 8). Two patients (14%) developed vaginal stenosis, which responded well to dilatation, and none of the patients had re-accumulation of the fluid during the follow-up period. Single-stage abdomino-perineal pull-through vaginoplasty in neonates with complicated distal vaginal atresia (complicated with obstructive uropathy, intestinal obstruction, urinary tract infection, or systemic sepsis) is an appropriate and feasible technique with a satisfactory outcome. Treatment study. IV.

Novel Bottom-Side Polished PCF-Based Plasmonic Biosensor for Early Detection of Hazardous Cancerous Cells.

This work presents a single-core bowl-shaped bottom-side polished (BSP) photonic crystal fiber (PCF) sensor based on surface plasmon resonance (SPR) concept for the early detection of hazardous cancer cells in human blood, skin, cervical, breast, and adrenal glands. We have studied liquid samples of cancer-affected and healthy samples with their concentrations/refractive indices in the sensing medium. To induce a plasmonic effect in the PCF sensor, the bottom flat section of a silica PCF fiber is coated with a 40nm plasmonic material, such as gold. To strengthen this effect, a thin TiO2 layer of 5 nm is sandwiched between fiber and gold as it strongly holds gold nanoparticles with smooth fiber surface. When the cancer-affected sample is introduced to the sensor's sensing medium, it produces a different absorption peak in the form of a resonance wavelength than the healthy sample. This reallocation of the absorption peak is used to determine sensitivity. Hence, the obtained sensitivities for blood cancer, cervical cancer, adrenal gland cancer, skin cancer, and breast cancer (type-1and type-2) cells are 22,857nm/RIU, 20000nm/RIU, 20714nm/RIU, 20000nm/RIU, 21428nm/RIU, and 25000nm/RIU, respectively, with highest detection limit 0.024. These strong findings indicate that our proposed cancer sensor PCF is a viable choice for early cancer cell detection.

Beta thalassemia revealing hypothyroidism: A case report

Thalassemia is a condition that affects hemoglobin synthesis and is one of the most Common hereditary illnesses in the world. Patients with thalassemia major require several blood transfusions. Multiple blood transfusions cause thyroid dysfunction, which leads to iron excess. We report the case of 35-year-old, followed in hematology for deep iron deficiency anemia who has benefited from a transfusion repeatedly diagnosed with beta thalassemia. At the interrogation, the patient reports a moderate gain of weight not quantified, hair loss and sensations of chills, chronic constipation, without other associated signs including no other signs of hypersecretion or anterior pituitary hyposecretion, no tumor SD. The physical examination finds a conscious patient, Normocardium, normal build, dysmorphic SD, palpable thyroid not increased in size. Microcytic hypochromic anemia, TSH at 10 mIU/l (0.35 -5.1) mIU / l, T4 at 10.6 pmol / l (10.6-19.4) pmol / l T3 to 2.88 pmol / l (3.8-8.4) pmol / l. Objective cervical ultrasound thyroid gland increased in size at the expense of the thyroid lobe with thyroid nodules classified EU-TIRADS 2 and 3. The patient was put on levothyrox 75ug/d. Thyroid disorders are common in β-thalassemia patients who have been transfused multiple times.

Estrogen induces genomic instability in high-risk HPV-infected cervix and promotes the carcinogenesis of cervical adenocarcinoma

High-risk human papillomavirus (HPV) infection is the major cause of cervical cancer. However, the factors that modulate the process from infection to carcinogenesis are poorly understood. Although cervical cancer is clinically considered an estrogen-independent tumor, the role of estrogen in cervical cancer, particularly cervical adenocarcinoma, remains controversial. In this study, we showed that estrogen/GPR30 signaling induced genomic instability, which leads to carcinogenesis in high-risk HPV-infected endocervical columnar cell lines.The expression of estrogen receptors in a normal cervix was confirmed through immunohistochemical analysis which showed that G protein-coupled receptor 30 (GPR30) was predominantly expressed in endocervical glands and estrogen receptor-α (ERα) was expressed at higher levels in the squamous epithelium than in the cervical gland. E2 increased the proliferation of cervical cell lines, particularly normal endocervical columnar and adenocarcinoma cells via GPR30 rather than ERα, and increased the accumulation of DNA double-strand breaks (DSBs) in high-risk HPV-E6-expressing cells. The increase in DSBs was caused by the impairment of Rad 51 and accumulation of topoisomerase-2-DNA complexes under HPV-E6 expression. In addition, chromosomal aberrations increased in cells with E2-induced DSB accumulation. Collectively, we conclude that E2 exposure in high-risk HPV-infected cervical cells increases DSBs, leading to genomic instability and thus carcinogenesis via GPR30.

A proteasomal β5 subunit of Haemonchus contortus with a role in the growth, development and life span

BackgroundThe proteasome in eukaryotic cells can degrade a variety of proteins and plays an important role in regulating the cell cycle, cell survival and apoptosis. The proteasome receives much attention as a potential chemotherapeutic target for treatment of a variety of infectious parasitic diseases, but few studies of proteasomes have been done on parasitic nematodes.MethodsA proteasomal β5 subunit encoding gene (named Hc-pbs-5) and its inferred product (Hc-PBS-5) in Haemonchus contortus were identified and characterized in this study. Then, the transcriptional profiles and anatomical expression were studied using an integrated molecular approach. Finally, a specific proteasome inhibitor bortezomib (BTZ), together with RNA interference (RNAi), was employed to assess the function of Hc-PBS-5.ResultsBioinformatic analysis revealed that the coding sequence of Hc-pbs-5 was 855 bp long and encoded 284 amino acids (aa). The predicted protein (Hc-PBS-5) had core conservative sequences (65–250 aa) belonging to N-terminal nucleophile (Ntn) family of hydrolases. Real-time PCR results revealed that Hc-pbs-5 was continuously transcribed in eight developmental stages with higher levels at the infective third-stage larvae (L3s) and adult males of H. contortus. Immunohistochemical results revealed that Hc-PBS-5 was expressed in intestine, outer cuticle, muscle cells under the outer cuticle, cervical glands and seminal vesicles of male adults and also in intestine, outer cuticle, cervical glands, uterine wall, eggs and ovaries of female adults of H. contortus. BTZ could reduce proportions of egg hatching, and the fourth-stage larvae (L4s) developed from the exsheathed L3s (xL3s) of H. contortus. In addition, silencing Hc-pbs-5 by soaking the specific double-stranded RNA (dsRNA) could decrease the transcription of Hc-pbs-5 and result in fewer xL3s developing to L4s in vitro.ConclusionsThese results indicate that proteasomal β5 subunit plays an important role in the growth, development and life span of H. contortus.Graphical

Gestational age‐related changes in cervical gland length in normal singleton pregnancies from 17 to 36 weeks of gestation

To determine the gestational age-related changes in cervical gland length in relation to cervical length (CL) in normal singleton pregnancies. We studied 363 women with an uncomplicated singleton pregnancy (188 nulliparous and 175 multiparous women with one or more previous transvaginal deliveries). A total of 1138 cervical gland and CLs were measured longitudinally at 17-36 weeks of gestation using transvaginal ultrasonography along the curvature from the external os to the lower uterine segment and the internal end of the cervical gland area (CGA), respectively. Gestational age-related changes in cervical gland and CLs and their relationships were analyzed using a linear mixed model. Cervical gland and CLs decreased in different ways with advancing gestation depending on parity, and their changes were related to each other. The CGAs in nulliparous women were longer than those in multiparous women at 17-25 weeks of gestation (p < 0.05), but with no differences thereafter. CLs in multiparous women were different from those in nulliparous women at 17-23 and 35-36 weeks (p < 0.05), but there were no differences at 24-34 weeks. The cervix did not shorten compared with the CGA throughout the observational periods in nulliparous and multiparous women. Shortening of the cervix indicates changes to the lower uterine segment in normal pregnancies. The cervical gland region can be a useful marker representing the true cervix beyond 25 weeks of gestation, irrespective of parity.

Tissue expression analysis of cervical mucus proteome.

Cervical mucus is a viscous fluid functioning as a cervix plug. Products of the endometrial and cervical glands can be detected in the cervical mucus. Cervical mucus is further enriched with transudate originating from the fallopian tubes and proteins originating from the ovaries, peritoneum and distant tissues. With increasing levels of ovarian estrogens, the properties of cervical mucus for possible collection and processing change appropriately. For these reasons, we chose a group of 10 patients treated in the center of assisted reproduction by controlled ovarian stimulation for in vitro fertilization. This study focuses on the proteomic characterization of cervical mucus and localizes the possible sources of the identified proteins. The most abundant proteins were extracellular proteins, mainly mucins; however, most of the identified proteins, present usually in lower quantities, were of intracellular origin. The tissue analysis revealed that proteins from female reproductive organs are also expressed in other tissues in addition to female reproductive organs, but also proteins specific to the testis, liver, placenta, retina, and cerebellum. This study confirms the suitability and high potential of cervical mucus as a source of proteomic bio-markers not only for the dia-gnosis of the female reproductive tract.

Antimonene-Coated Uniform-Waist Tapered Fiber Optic Surface Plasmon Resonance Biosensor for the Detection of Cancerous Cells: Design and Optimization.

For early-stage cancer detection, a novel design of graphene-antimonene-coated uniform-waist tapered fiber optic surface plasmon resonance (SPR) biosensor is demonstrated. The proposed optical biosensor outperforms over a wide range of refractive index (RI) variations including biological solutions and is designed to detect various cancerous cells in the human body whose RIs are in the range of 1.36-1.4. Here, antimonene is used to enhance the performance of the designed SPR sensor for sensing cancer analytes because of its high binding energy toward adsorption of biomolecules and large active surface area. The design and analysis of the sensor are done with the help of a transfer matrix method-based simulation platform, and the effect of the taper ratio is also studied. The performance of the proposed SPR biosensor is evaluated with performance parameters such as sensitivity, full width at half maximum, detection accuracy (DA), figure of merit (FOM), and limit of detection (LOD). The numerical results show that the designed sensor is able to provide a sensitivity of 7.3465, 10.9250, 11.8914, and 15.2414 μm/RIU, respectively, for sensing skin, cervical, blood, and adrenal gland cancer with a maximum FOM of 131.1525 RIU-1, DA of 14.2126 μm-1, and LOD of 7.2 × 10-5 RIU. Based on the derived results, the authors believe that the designed SPR sensor could practically find its potential applications in the field of medical science for the early-stage diagnosis of cancer and hence, opens a new window in the field of biosensing.

Pathological roles of antimicrobial peptides and pro-inflammatory factors secreted from the cervical epithelium in Gardnerella vaginalis-abundant vaginal flora in pregnancy

Bacterial vaginosis due to Gardnerella vaginalis (GV) is one of the main causes of preterm birth. Antimicrobial function of the cervical glands prevents ascending pathogen infection. This study investigated the effect of GV on the cervical gland cells. We examined the correlation between GV and neutrophil elastase in the cervical mucous obtained from pregnant women’s clinical samples. Culture supernatants (sup) of GV and Lactobacillus crispatus (LC) were added to human immortalized cervical gland cells (EndoCx). Quantitative reverse transcription PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to examine the effects on the production of antimicrobial peptides (AMPs), secretory leukocyte peptidase inhibitor (SLPI), and Elafin. mRNA microarray analysis revealed the expression profile of GV-exposed EndoCx. Moreover, the antimicrobial activity of Elafin against LC and GV was investigated. In the clinical samples, neutrophil elastase was increased in the GV-positive cervical mucous. In an in vitro assay, RT-qPCR and ELISA showed that GV-sup enhanced the secretion of Elafin, but not SLPI, from EndoCx, whereas LC-sup did not. mRNA microarray assay and ELISA results demonstrated that GV-sup enhanced the proinflammatory pathway and interleukin (IL)− 8 secretion from EndoCx as well as cell adhesion and tight junction pathways. Moreover, GV-sup directly enhanced Elafin and IL-8 secretion from the cervical gland cells. In the GV-abundant vaginal flora, IL-8 level increased the neutrophil elastase activity and Elafin inhibited the elastase activity to protect from tissue damage and infection. Thus, the balance of IL-8-induced neutrophil and Elafin-induced antiprotease activities may be crucial in preterm labor.

Proteome Mapping of Cervical Mucus and Its Potential as a Source of Biomarkers in Female Tract Disorders.

Cervical mucus (CM) is a viscous fluid that is produced by the cervical glands and functions as a uterine cervix plug. Its viscosity decreases during ovulation, providing a window for non-invasive sampling. This study focuses on proteomic characterization of CM to evaluate its potential as a non-invasively acquired source of biomarkers and in understanding of molecular (patho)physiology of the female genital tract. The first objective of this work was to optimize experimental workflow for CM processing and the second was to assess differences in the proteomic composition of CM during natural ovulatory cycles obtained from intrauterine insemination (IUI) cycles and in vitro fertilization (IVF) cycles with controlled ovarian hyperstimulation. Proteomic analysis of CM samples revealed 4370 proteins involved in processes including neutrophil degranulation, cellular stress responses, and hemostasis. Differential expression analysis revealed 199 proteins enriched in IUI samples and 422 enriched in IVF. The proteins enriched in IUI were involved in phosphatidic acid synthesis, responses to external stimulus, and neutrophil degranulation, while those enriched in IVF samples were linked to neutrophil degranulation, formation of a cornified envelope and hemostasis. Subsequent analyses clarified the protein composition of the CM and how it is altered by hormonal stimulation of the uterus.