ABSTRACT
Satellite-derived chlorophyll-a concentration (Chl-a) is essential for assessing environmental conditions, yet its application in the optically complex waters of the eastern Yellow Sea (EYS) is challenged. This study refines the Chl-a algorithm for the EYS employing a switching approach based on normalized water-leaving radiance at 555 nm wavelength according to turbidity conditions to investigate phytoplankton bloom patterns in the EYS. The refined Chl-a algorithm (EYS algorithm) outperforms prior algorithms, exhibiting a strong alignment with in situ Chl-a. Employing the EYS algorithm, seasonal and bloom patterns of Chl-a are detailed for the offshore and nearshore EYS areas. Distinct seasonal Chl-a patterns and factors influencing bloom initiation differed between the areas, and the peak Chl-a during the bloom period from 2018 to 2020 was significantly lower than the average year in both areas. Specifically, bimodal and unimodal peak patterns in Chl-a were observed in the offshore and nearshore areas, respectively. By investigating the relationships between environmental factors and bloom parameters, we identified that major controlling factors governing bloom initiation were mixed layer depth (MLD) and suspended particulate matter (SPM) in the offshore and nearshore areas, respectively. Additionally, this study proposed that the recent decrease in the peak Chl-a might be caused by rapid environmental changes such as the warming trend of sea surface temperature (SST) and the limitation of nutrients. For example, external forcing, phytoplankton growth, and nutrient dynamics can change due to increased SST and limitation of nutrients, which can lead to a decrease in Chl-a. This study contributes to understanding phytoplankton dynamics in the EYS, highlighting the importance of region-specific considerations in comprehending Chl-a patterns and bloom dynamics.
Subject(s)
Chlorophyll A , Eutrophication , Phytoplankton , Algorithms , China , Chlorophyll/analysis , Chlorophyll A/analysis , Environmental Monitoring , Oceans and Seas , Phytoplankton/physiology , Phytoplankton/growth & development , Satellite Imagery , Seasons , Seawater/chemistryABSTRACT
AIM: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.
Subject(s)
Autism Spectrum Disorder , Microsatellite Repeats , Humans , Autism Spectrum Disorder/genetics , Microsatellite Repeats/genetics , Male , Female , Cerebral Cortex/pathology , Phenotype , Child , Whole Genome Sequencing , Deep Learning , Severity of Illness Index , Adult , DNA Repeat Expansion/geneticsABSTRACT
Harnessing the key intermediates in metal-catalyzed reactions is one of the most essential strategies in the development of selective organic transformations. The nitrogen group transfer reactivity of metal-nitrenoids to ubiquitous C-H bonds allows for diverse C-N bond formation to furnish synthetically valuable aminated products. In this study, we present an unprecedented reactivity of iridium and ruthenium nitrenoids to generate remote carbocation intermediates, which subsequently undergo nucleophile incorporation, thus developing a formal γ-C-H functionalization of carboxylic acids. Mechanistic investigations elucidated a unique singlet metal-nitrenoid reactivity to initiate an abstraction of γ-hydride to form the carbocation intermediate that eventually reacts with a broad range of carbon, nitrogen, and oxygen nucleophiles, as well as biorelevant molecules. Alternatively, the same intermediate can lead to deprotonation to afford ß,γ-unsaturated amides in a less nucleophilic solvent.
ABSTRACT
Despite advances in microfabrication, compact spectrometers still face challenges in shrinking their size without sacrificing optical performance. Here, the solid immersion grating microspectrometer (SIG-µSPEC) for high spectral resolution in a broad operational wavelength range is reported. The spectroscopic module incorporates a silicon microslit, index-matched lens, plane mirrors, solid immersion grating (SIG), and a CMOS line sensor within a small form factor. The SIG facilitates high angular dispersion of light on a planar focal plane, resulting in an average spectral resolution of 5.8 nm, with over 76% maximum sensitivity from 400 to 800 nm. SIG-µSPEC measures the spectral reflectance of fruits at different ripening stages, clearly revealing changes in the chlorophyll absorption band. The measured spectrum is further utilized for the precise prediction of the soluble solid content (SSC) levels, achieving a high correlation (R2 = 0.91) and a ratio of prediction-to-deviation of 2.36. This compact microspectrometer holds the potential for precise and non-invasive spectral analysis across point-of-care fields.
ABSTRACT
RATIONALE: Carcinoid tumors, derived from the cells of the disseminated neuroendocrine system, are rare, slow-growing neuroendocrine neoplasms that display a relatively indolent disease course. The majority of carcinoids are found within the gastrointestinal tract and bronchopulmonary system. Primary ovarian carcinoids are rare and account for merely 1% of all carcinoid tumors. We describe our experience of a rare case of primary ovarian carcinoid, presenting as chronic constipation, with no other carcinoid symptoms such as flushing, diarrhea, and wheezing. PATIENT CONCERNS: A 51-year-old postmenopausal woman with chronic constipation visited the clinic for routine check-up of her preexisting uterine fibroids. She had undergone hemorrhoidectomy 3 years ago. Physical examination revealed a soft abdomen without direct or rebound tenderness. Transvaginal ultrasonography revealed two subserosal fibroids, which had increased in size compared with previous ultrasonographic findings. A 3 cm hyperechoic mass was also detected in the right ovary. Her blood and urine tests were unremarkable, with no ascites in the pelvic cavity. She had a normal CA-125 level of 5.5 units/mL. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: The patient underwent a robot-assisted hysterectomy and right salpingo-oophorectomy because of enlarging fibroids and the right ovarian mass. Subsequently, based on the pathological and immunohistochemical findings, she was diagnosed with a primary ovarian carcinoid. The mass consisted of the insular and trabecular types of tumor cells. It was positive for pan-cytokeratin and synaptophysin, and the Ki-67 proliferation index was less than 1%. A follow-up positron emission tomography-computed tomography revealed no distant metastasis. Six months postoperatively, the patient was doing well without any signs of recurrence. LESSONS: Primary ovarian carcinoids without teratoma components are rare. It is crucial to make an accurate diagnosis based on the immunohistochemical staining results. Diagnosis in the early stages of the disease are associated with a favorable prognosis, but regular follow-up is mandatory.
Subject(s)
Carcinoid Tumor , Ovarian Neoplasms , Humans , Female , Middle Aged , Ovarian Neoplasms/complications , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Salpingo-oophorectomy , Carcinoid Tumor/complications , Carcinoid Tumor/diagnosis , Carcinoid Tumor/surgery , ConstipationABSTRACT
BCR-ABL inhibition is an effective therapeutic approach for the treatment of chronic myeloid leukaemia (CML). Herein, we report the discovery of AKE-72 (5), a diarylamide 3-aminoindazole, as a potent pan-BCR-ABL inhibitor, including the imatinib-resistant mutant T315I. A focussed array of compounds 4a, 4b, and 5 has been designed based on our previously reported indazole I to improve its BCR-ABLT315I inhibitory activity. Replacing the morpholine moiety of I with the privileged tail (4-ethylpiperazin-1-yl)methyl afforded 5 (AKE-72) with IC50 values of < 0.5 nM, and 9 nM against BCR-ABLWT and BCR-ABLT315I, respectively. Moreover, AKE-72 potently inhibited a panel of other clinically important mutants in single-digit nanomolar IC50 values. AKE-72 elicited remarkable anti-leukemic activity against K-562 cell line (GI50 < 10 nM, TGI = 154 nM). In addition, AKE-72 strongly inhibited the proliferation of Ba/F3 cells expressing native BCR-ABL or its T315I mutant. Overall, AKE-72 may serve as a promising candidate for the treatment of CML, including those harbouring T315I mutation.
Subject(s)
Indazoles , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Indazoles/pharmacology , Drug Resistance, Neoplasm , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Fusion Proteins, bcr-abl/genetics , Fusion Proteins, bcr-abl/metabolism , Benzamides/pharmacology , Cell Line, Tumor , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Mutation , Cell Proliferation , ApoptosisABSTRACT
Throughout an individual's lifetime, genomic alterations accumulate in somatic cells1-11. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome12-14, is poorly understood in normal cells. Here we explored the whole-genome sequences of 899 single-cell clones established from three different cell types collected from 28 individuals. We identified 1,708 somatic L1 retrotransposition events that were enriched in colorectal epithelium and showed a positive relationship with age. Fingerprinting of source elements showed 34 retrotransposition-competent L1s. Multidimensional analysis demonstrated that (1) somatic L1 retrotranspositions occur from early embryogenesis at a substantial rate, (2) epigenetic on/off of a source element is preferentially determined in the early organogenesis stage, (3) retrotransposition-competent L1s with a lower population allele frequency have higher retrotransposition activity and (4) only a small fraction of L1 transcripts in the cytoplasm are finally retrotransposed in somatic cells. Analysis of matched cancers further suggested that somatic L1 retrotransposition rate is substantially increased during colorectal tumourigenesis. In summary, this study illustrates L1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime.
Subject(s)
Colon , DNA Transposable Elements , Intestinal Mucosa , Retroelements , Humans , Carcinogenesis/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA Transposable Elements/genetics , Genomics , Long Interspersed Nucleotide Elements/genetics , Retroelements/genetics , Aging/genetics , Gene Frequency , Mosaicism , Epigenomics , Genome, Human/genetics , Colon/metabolism , Intestinal Mucosa/metabolism , Embryonic Development/geneticsABSTRACT
Basal cell carcinoma (BCC) is a major non-melanoma skin cancer, and its incidence is increasing worldwide. Although the main etiology is sun exposure, BCC may develop in sun-protected areas such as the vulva. The sonic hedgehog signaling pathway mutation may explain the mechanism underlying the occurrence of vulvar BCC. Owing to the rarity of metastases, wide local excision is an appropriate treatment option. Here, we report the cases two postmenopausal women with vulvar BCC who were surgically treated.
ABSTRACT
Compact spectrometers facilitate non-destructive and point-of-care spectral analysis. Here we report a single-pixel microspectrometer (SPM) for visible to near-infrared (VIS-NIR) spectroscopy using MEMS diffraction grating. The SPM consists of slits, electrothermally rotating diffraction grating, spherical mirror, and photodiode. The spherical mirror collimates an incident beam and focuses the beam on the exit slit. The photodiode detects spectral signals dispersed by electrothermally rotating diffraction grating. The SPM was fully packaged within 1.7 cm3 and provides a spectral response range of 405â nm to 810â nm with an average 2.2â nm spectral resolution. This optical module provides an opportunity for diverse mobile spectroscopic applications such as healthcare monitoring, product screening, or non-destructive inspection.
ABSTRACT
This study aimed to investigate the survival outcomes and prognostic factors associated with the surgical approach in patients with early-stage cervical cancer. We retrospectively analyzed 245 patients with stage IB1 to IIA2 cervical cancer who underwent radical hysterectomy with pelvic lymphadenectomy between 2004 and 2019 at Dong-A University Hospital. A total of 59 patients underwent minimally invasive surgery (MIS), and 186 patients underwent open surgery. There were no significant differences between the 2 groups, except for stromal invasion (Pâ <â .001), lymphovascular invasion (Pâ =â .001), and requirement for adjuvant therapy (Pâ <â .001). There were no significant differences in disease-free survival (DFS) and overall survival (OS) based on the surgical approach. However, multivariate analyses showed MIS was an independent poor prognostic factor of DFS (adjusted hazard ratio [HR]: 230; 95% confidence interval [CI]: 086-0.614, Pâ =â .003) and OS (adjusted HR: 135; 95% CI: 041-0.451, Pâ =â .001). Adjuvant therapy was a poor prognostic factor for DFS (adjusted HR: 6.546; 95% CI: 1.384-30.952; Pâ =â .018), and deep stromal invasion was a poor prognostic factor for OS (adjusted HR: 8.715; 95% CI: 1.636-46.429; Pâ =â .01). MIS may be an independent poor prognostic factor for DFS and OS in patients who undergo radical hysterectomy for early-stage cervical cancer.
Subject(s)
Uterine Cervical Neoplasms , Female , Humans , Retrospective Studies , Neoplasm Staging , Uterine Cervical Neoplasms/pathology , Disease-Free Survival , Hysterectomy , Minimally Invasive Surgical ProceduresABSTRACT
The design of kinase inhibitors targeting the oncogenic kinase BCR-ABL constitutes a promising paradigm for treating chronic myeloid leukaemia (CML). Nevertheless, the efficacy of imatinib, the first FDA-approved targeted therapy for CML, is curbed by the emergence of resistance. Herein, we report the identification of the 2-methoxyphenyl ureidobenzothiazole AK-HW-90 (2b) as a potent pan-BCR-ABL inhibitor against imatinib-resistant mutants, particularly T315I. A concise array of six compounds 2a-f was designed based on our previously reported benzothiazole lead AKE-5l to improve its BCR-ABLT315I inhibitory activity. Replacing the 6-oxypicolinamide moiety of AKE-5l with o-methoxyphenyl and changing the propyl spacer with phenyl afforded 2a and AK-HW-90 (2b) with IC50 values of 2.0 and 0.65 nM against BCR-ABLT315I, respectively. AK-HW-90 showed superior anticancer potency to imatinib against multiple cancer cells (NCI), including leukaemia K-562. The obtained outcomes offer AK-HW-90 as a promising candidate for the treatment of CML and other types of cancer.
Subject(s)
Fusion Proteins, bcr-abl , Pyrimidines , Imatinib Mesylate/pharmacology , Fusion Proteins, bcr-abl/genetics , Pyrimidines/pharmacology , Piperazines/pharmacology , Benzamides/pharmacology , ApoptosisABSTRACT
The emergence of cancer resistance to targeted therapy represents a significant challenge in cancer treatment. Therefore, identifying new anticancer candidates, particularly those addressing oncogenic mutants, is an urgent medical demand. A campaign of structural modifications has been conducted to further optimize our previously reported 2-anilinoquinoline-diarylamides conjugate VII as a B-RAFV600E/C-RAF inhibitor. Considering the incorporation of a methylene bridge between the terminal phenyl and cyclic diamine, focused quinoline-based arylamides have been tailored, synthesized, and biologically evaluated. Among them, the 5/6-hydroxyquinolines 17b and 18a stood out as the most potent members, with IC50 values of 0.128 µM, 0.114 µM against B-RAFV600E, and 0.0653 µM, 0.0676 µM against C-RAF. Most importantly, 17b elicited remarkable inhibitory potency against the clinically resistant B-RAFV600K mutant with an IC50 value of 0.0616 µM. The putative binding mode of 17b and 18a were studied by molecular docking and molecular dynamics (MD). Moreover, the antiproliferative activity of all target compounds has been examined over a panel of NCI-60 human cancer cell lines. In agreement with cell-free assays, the designed compounds exerted superior anticancer impact over the lead quinoline VII against all cell lines at a 10 µM dose. Notably, both 17b and 18b showed highly potent antiproliferative activity against melanoma cell lines with growth percent under -90% (SK-MEL-29, SK-MEL-5, and UACC-62) at a single dose, while 17b maintained potency with GI50 values of 1.60-1.89 µM against melanoma cell lines. Taken together, 17b, a promising B-RAFV600E/V600K and C-RAF kinase inhibitor, may serve as a valuable candidate in the arsenal of anticancer chemotherapeutics.
Subject(s)
Antineoplastic Agents , Melanoma , Quinolones , Humans , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation , Drug Screening Assays, Antitumor , Melanoma/drug therapy , Molecular Docking Simulation , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins B-raf/metabolism , Quinolones/pharmacology , Structure-Activity RelationshipABSTRACT
OBJECTIVE: Brain somatic mutations in mTOR pathway genes are a major genetic etiology of focal cortical dysplasia type II (FCDII). Despite a greater ability to detect low-level somatic mutations in the brain by deep sequencing and analytics, about 40% of cases remain genetically unexplained. METHODS: We included 2 independent cohorts consisting of 21 patients with mutation-negative FCDII without apparent mutations on conventional deep sequencing of bulk brain. To find ultra-low level somatic variants or structural variants, we isolated cells exhibiting phosphorylation of the S6 ribosomal protein (p-S6) in frozen brain tissues using fluorescence-activated cell sorting (FACS). We then performed deep whole-genome sequencing (WGS; >90×) in p-S6+ cells in a cohort of 11 patients with mutation-negative. Then, we simplified the method to whole-genome amplification and target gene sequencing of p-S6+ cells in independent cohort of 10 patients with mutation-negative followed by low-read depth WGS (10×). RESULTS: We found that 28.6% (6 of 21) of mutation-negative FCDII carries ultra-low level somatic mutations (less than 0.2% of variant allele frequency [VAF]) in mTOR pathway genes. Our method showed ~34 times increase of the average mutational burden in FACS mediated enrichment of p-S6+ cells (average VAF = 5.84%) than in bulky brain tissues (average VAF = 0.17%). We found that 19% (4 of 21) carried germline structural variations in GATOR1 complex undetectable in whole exome or targeted gene sequencing. CONCLUSIONS: Our method facilitates the detection of ultra-low level somatic mutations, in specifically p-S6+ cells, and germline structural variations and increases the genetic diagnostic rate up to ~80% for the entire FCDII cohort. ANN NEUROL 2023;93:1082-1093.
Subject(s)
Epilepsy , Focal Cortical Dysplasia , Humans , TOR Serine-Threonine Kinases/genetics , Epilepsy/genetics , Mutation/geneticsABSTRACT
Variant callers typically produce massive numbers of false positives for structural variations, such as cancer-relevant copy-number alterations and fusion genes resulting from genome rearrangements. Here we describe an ultrafast and accurate detector of somatic structural variations that reduces read-mapping costs by filtering out reads matched to pan-genome k-mer sets. The detector, which we named ETCHING (for efficient detection of chromosomal rearrangements and fusion genes), reduces the number of false positives by leveraging machine-learning classifiers trained with six breakend-related features (clipped-read count, split-reads count, supporting paired-end read count, average mapping quality, depth difference and total length of clipped bases). When benchmarked against six callers on reference cell-free DNA, validated biomarkers of structural variants, matched tumour and normal whole genomes, and tumour-only targeted sequencing datasets, ETCHING was 11-fold faster than the second-fastest structural-variant caller at comparable performance and memory use. The speed and accuracy of ETCHING may aid large-scale genome projects and facilitate practical implementations in precision medicine.
Subject(s)
High-Throughput Nucleotide Sequencing , Neoplasms , Humans , High-Throughput Nucleotide Sequencing/methods , Genome , Sequence Analysis, DNA/methodsABSTRACT
Cervical adenocarcinomas constitute for approximately 10%-20% of all invasive cervical cancers. Villoglandular adenocarcinomas (VGAs) are a rare subtype of cervical adenocarcinoma, representing approximately 5% of all cases of cervical adenocarcinomas. Herein, we report the case of a 49-year-old perimenopausal woman successfully treated for VGA. The patient presented to the hospital with a primary complaint of vaginal discharge persisting for 7 months with worsening symptoms. She had no underlying medical conditions or history of oral contraceptive use. A punch biopsy revealed an adenocarcinoma, and a human papillomavirus (HPV) test indicated positive for HPV-16. The patient underwent a radical hysterectomy with bilateral pelvic lymph node dissection, and a pathological diagnosis of VGA was established. After surgery, the patient underwent a 6-week course of concurrent chemoradiotherapy with cisplatin. During the 42 months of follow-up, no signs of disease recurrence or metastasis were observed. Because of the limitations of specimen acquisition, achieving a precise diagnosis through cervicovaginal cytology and punch biopsy is challenging. Instead, conization should be considered to prevent misdiagnosis.
ABSTRACT
BACKGROUND: High-intensity focused ultrasound (HIFU) ablation is a minimally invasive approach in gynecology that is used to manage uterine fibroids. Although this procedure is safe and effective, adverse outcomes are becoming a major problem. CASE SUMMARY: We present a case of ventral hernia that occurred as a rare and delayed complication of HIFU ablation for uterine fibroids treatment. The patient came to the hospital with abdominal bloating that occurred 6 mo after ultrasound-guided HIFU ablation for managing uterine fibroids. The ventral hernia, which occurred due to atrophied muscle layers following the procedure, was confirmed by imaging studies and intraoperative findings. She required a hernia repair with mesh and hysterectomy for definitive treatment of uterine fibroid. CONCLUSION: High-intensity ultrasound ablation should be performed only on appropriate candidates. Patients should be educated about potential complications of the procedure and the possibility of subsequent treatment. Post-procedural long-term follow-up for detecting delayed adverse effects is important.
ABSTRACT
INTRODUCTION: Myeloid sarcoma (MS) is an extramedullary tumor that consists of myeloblasts and rarely involves the female reproductive organs. Intestinal Behçet's disease (BD) is a chronic, inflammatory illness that is often associated with myelodysplastic syndrome (MDS). When MDS is diagnosed, some patients with intestinal BD experience synchronous gastrointestinal flares. CASE PRESENTATION: We report the case of a 49-year-old woman who presented with vaginal bleeding and an incidentally identified MS in the uterine cervix. Subsequent bone marrow biopsy showed simultaneous MDS without chromosomal abnormalities. This is the first reported case of concomitant MS, myelodysplastic disease, and intestinal BD. CONCLUSIONS: The accurate diagnosis of MSs that develop at non-predominant sites is crucial for a positive patient prognosis. MDS should be suspected in patients with a history of intestinal BD diagnosed with MS.
Subject(s)
Behcet Syndrome , Intestinal Diseases , Myelodysplastic Syndromes , Sarcoma, Myeloid , Uterine Cervical Neoplasms , Humans , Female , Middle Aged , Behcet Syndrome/complications , Behcet Syndrome/diagnosis , Behcet Syndrome/pathology , Sarcoma, Myeloid/complications , Sarcoma, Myeloid/diagnosis , Uterine Cervical Neoplasms/complications , Uterine Cervical Neoplasms/diagnosis , Trisomy , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/pathology , Intestinal Diseases/complications , Intestinal Diseases/diagnosisABSTRACT
OBJECTIVE: Triphenyl phosphate (TPHP) is one of the most commonly used organophosphorus flame retardants that may accumulate in the environment. However, its effects on human reproductive organs have not been well studied. We aimed to investigate the in vitro effects of TPHP in human Ishikawa endometrial cancer cells to elucidate how TPHP exposure disrupts intracellular signaling and cell proliferation in reproductive tissues. METHODS: Human Ishikawa endometrial cancer cells were exposed to TPHP. RESULTS: Exposure to TPHP elevated the levels of estrogen receptor (ER) α and progesterone receptor-B and reduced ER ß in human Ishikawa endometrial cancer cells. TPHP stimulated phosphoinositide 3-kinase/protein kinase B and mitogenactivated protein kinase/ extracellular signal-regulated kinases 1/2 kinase signaling, which may contribute to the activation of ER function and induce nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in human Ishikawa endometrial cancer cells. Activated ER and NF-κB stimulate the expression of cyclin D1/ cyclin-dependent kinase (CDK) 4/CDK6, indicating cell cycle progression and proliferation. CONCLUSION: This report may provide new information on the molecular mechanisms underlying how TPHP exposure dysregulates the cellular physiology of the human endometrium.
ABSTRACT
COVID-19 is hopefully approaching its end in many countries as herd immunity develops and weaker strains of SARS-CoV-2 dominate. However, a new concern occurs over the long-term effects of COVID-19, collectively called "Long COVID", as some symptoms of the nervous system last even after patients recover from COVID-19. This review focuses on studies of anosmia, i.e., impairment of smell, which is the most common sensory defect during the disease course and is caused by olfactory dysfunctions. It remains mysterious how the olfactory functions are affected since the virus can't invade olfactory receptor neurons. We describe several leading hypotheses about the mystery in hope to provide insights into the pathophysiology and treatment strategies for anosmia.