Construction and validation of a risk-prediction model for chemotherapy-related cognitive impairment in patients with breast cancer.

PURPOSE: To identify risk factors of chemotherapy-related cognitive impairment (CRCI) and construct and validate a visual prediction model of such for patients with breast cancer. METHODS: A multicenter, descriptive, and cross-sectional design was adopted. Data were collected from ten public tertiary hospitals in China. Cognitive function was assessed by using Functional Assessment of Cancer Therapy-cognitive function. Socio-demographic, clinical, psychological, and physical indicators were also assessed. The logistic prediction model was constructed by fivefold cross-validation. Then, a nomogram was utilized to visualize the prediction model, which was also evaluated via discrimination, calibration, and decision curve analysis. RESULTS: A total of 71 breast cancer patients had CRCI with a prevalence of 9.58%. This visual prediction model was constructed based on education background, exercise frequency, chemotherapy times, and fatigue and demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.882. The calibration curve indicated good agreement between experimental and projected values, and the decision curve proved good clinical applicability. CONCLUSION: Education background, exercise frequency, chemotherapy times, and fatigue were associated with high incidence of CRCI. The prediction model exhibits superior performance and has promise as a useful instrument for assessing the likelihood of CRCI in breast cancer patients. IMPLICATIONS FOR CANCER SURVIVORS: Our findings could provide breast cancer survivors with risk screening based on CRCI predictors to implement prevention and early intervention, and help patients integrate into society and achieve comprehensive recovery.

Effects of a 12-week exercise-based intervention on weight management in overweight or obese breast cancer survivors: a randomized controlled trial.

PURPOSE: Breast cancer survivors face dual challenges: long-term sequelae of treatment and the risk of recurrent disease. Furthermore, obesity and a sedentary lifestyle can complicate both challenges. We aimed to assess the effect of a 12-week exercise-based weight-management program in overweight/obese breast cancer survivors. METHODS: A two-arm, single-blinded, randomized controlled trial was conducted among 60 overweight/obese, stage 0-III breast cancer survivors. During the 12-week program, the intervention group received weekly information support, fortnightly exercise prescriptions, including aerobic and resistance exercises to perform at home, and one dietary instruction. The control group received information support about weight management and exercise. Weight, body composition, and physical fitness data were collected at baseline, postintervention, and the 3-month follow-up. RESULTS: The intervention group showed significant improvements in body weight and all adiposity indices, including body mass index, waist circumference, and %body fat, in comparison with baseline (P < 0.001) and the control group (P < 0.05). Both groups showed no significant changes in fat-free mass during the 6-month period (P > 0.05). International Physical Activity Questionnaire scores and left grip strength increased significantly in the intervention group in comparison with the baseline (P < 0.01) and the control group (P < 0.05). Right grip strength, lower-body strength, and aerobic endurance showed no significant intergroup differences (P > 0.05). CONCLUSIONS: A combination of exercise prescription and weight-loss interventions yielded clinically meaningful weight loss in overweight/obese breast cancer survivors. These findings may facilitate the incorporation of home-based exercise and weight management into breast cancer treatment and survivorship care.

Unveiling adcyap1 as a protective factor linking pain and nerve regeneration through single-cell RNA sequencing of rat dorsal root ganglion neurons.

BACKGROUND: Severe peripheral nerve injury (PNI) often leads to significant movement disorders and intractable pain. Therefore, promoting nerve regeneration while avoiding neuropathic pain is crucial for the clinical treatment of PNI patients. However, established animal models for peripheral neuropathy fail to accurately recapitulate the clinical features of PNI. Additionally, researchers usually investigate neuropathic pain and axonal regeneration separately, leaving the intrinsic relationship between the development of neuropathic pain and nerve regeneration after PNI unclear. To explore the underlying connections between pain and regeneration after PNI and provide potential molecular targets, we performed single-cell RNA sequencing and functional verification in an established rat model, allowing simultaneous study of the neuropathic pain and axonal regeneration after PNI. RESULTS: First, a novel rat model named spared nerve crush (SNC) was created. In this model, two branches of the sciatic nerve were crushed, but the epineurium remained unsevered. This model successfully recapitulated both neuropathic pain and axonal regeneration after PNI, allowing for the study of the intrinsic link between these two crucial biological processes. Dorsal root ganglions (DRGs) from SNC and naïve rats at various time points after SNC were collected for single-cell RNA sequencing (scRNA-seq). After matching all scRNA-seq data to the 7 known DRG types, we discovered that the PEP1 and PEP3 DRG neuron subtypes increased in crushed and uncrushed DRG separately after SNC. Using experimental design scRNA-seq processing (EDSSP), we identified Adcyap1 as a potential gene contributing to both pain and nerve regeneration. Indeed, repeated intrathecal administration of PACAP38 mitigated pain and facilitated axonal regeneration, while Adcyap1 siRNA or PACAP6-38, an antagonist of PAC1R (a receptor of PACAP38) led to both mechanical hyperalgesia and delayed DRG axon regeneration in SNC rats. Moreover, these effects can be reversed by repeated intrathecal administration of PACAP38 in the acute phase but not the late phase after PNI, resulting in alleviated pain and promoted axonal regeneration. CONCLUSIONS: Our study reveals that Adcyap1 is an intrinsic protective factor linking neuropathic pain and axonal regeneration following PNI. This finding provides new potential targets and strategies for early therapeutic intervention of PNI.

Ferritinophagy-mediated apoptosis and paraptosis induction involved MAPK and PI3K/AKT pathway in mechanism of an iron chelator.

Melanoma cells were more resistant to ferroptosis with still poor therapy outcomes. Sensitizing melanoma cell to the ferroptosis inducer was a crucial strategy for treatment of melanoma. In the present study, 2,2'-di-pyridylketone hydrazone dithiocarbamate s-butyric acid (DpdtbA) displayed superior inhibitory activity than ferroptosis inducer Erastin in melanoma cells, which prompt us to explore the underlying mechanism. The analyses from flow cytometry and Western blot showed that the growth inhibition of DpdtbA against SK-MEL-28 and A375 cells involved apoptosis induction and G1 phase arrest. Surprisingly, the cytoplasmic vacuoles were found upon the treatment; transmission electron microscopy and endoplasmic reticulum (ER) staining revealed that the cytoplasmic vacuoles were in ER; while down-regulation of alix and requirement of protein synthesis suggested there was an occurrence of paraptosis. However, both NAC and 3-MA could significantly attenuate the cytoplasmic vacuolization and growth inhibition, hinting that both ROS and autophagy involved the paraptosis induction. The additional evidence revealed that there was an occurrence of continuous ferritinophagy, which was responsible for the ROS production. Downregulation of NCOA4 clearly attenuated the apoptosis and paraptosis induction. In addition, activation of MAPK involved regulation of paraptosis, but only ERK and JNK had role in the formation of cytoplasmic vacuoles and growth inhibition. Furthermore, a ROS dependent regulation of PI3K/AKT pathway was also involved. Taken together, our result firstly demonstrated that a continuous ferritinophagy contributed to the apoptosis and paraptosis induction, highlighting that the lysosomal labile iron pool had a crucial role in control of melanoma cell fate.

Greenhouse gas emissions from U.S. crude oil pipeline accidents: 1968 to 2020.

Crude oil pipelines are considered as the lifelines of energy industry. However, accidents of the pipelines can lead to severe public health and environmental concerns, in which greenhouse gas (GHG) emissions, primarily methane, are frequently overlooked. While previous studies examined fugitive emissions in normal operation of crude oil pipelines, emissions resulting from accidents were typically managed separately and were therefore not included in the emission account of oil systems. To bridge this knowledge gap, we employed a bottom-up approach to conducted the first-ever inventory of GHG emissions resulting from crude oil pipeline accidents in the United States at the state level from 1968 to 2020, and leveraged Monte Carlo simulation to estimate the associated uncertainties. Our results reveal that GHG emissions from accidents in gathering pipelines (~720,000 tCO2e) exceed those from transmission pipelines (~290,000 tCO2e), although significantly more accidents have occurred in transmission pipelines (6883 cases) than gathering pipelines (773 cases). Texas accounted for over 40% of total accident-related GHG emissions nationwide. Our study contributes to enhanced accuracy of the GHG account associated with crude oil transport and implementing the data-driven climate mitigation strategies.

DpdtpA, A Multi-metal Ion Chelator, Attenuates Tau Phosphorylation and Microglial Inflammatory Response via Regulating the PI3K/AKT/GSK-3ß Signal Pathways.

Tau protein hyperphosphorylation and formation of intracellular neurofibrillary tangles (NFTs) are one of the histopathological hallmarks of Alzheimer's disease (AD) and positively correlated with the severity of AD symptoms. NFTs contain a large number of metal ions that play an important role in regulating tau protein phosphorylation and AD progression. Extracellular tau induces primary phagocytosis of stressed neurons and neuronal loss by activating microglia. Here, we studied the effects of a multi-metal ion chelator, DpdtpA, on tau-induced microglial activation and inflammatory responses and the underlying mechanisms. Treatment with DpdtpA attenuated the increase in the expression of NF-κB and production of inflammatory cytokines, IL-1ß, IL-6 and IL-10, in rat microglial cells induced by expression of human tau40 proteins. Treatment with DpdtpA also suppressed tau protein expression and phosphorylation. Moreover, treatment with DpdtpA prevented tau-induced activation of glycogen synthase kinase-3ß (GSK-3ß) and inhibition of phosphatidylinositol-3-hydroxy kinase (PI3K)/AKT. Collectively, these results show that DpdtpA can attenuate tau phosphorylation and inflammatory responses of microglia by regulating the PI3K/AKT/GSK-3ß signal pathways, providing a new option to alleviate neuroinflammation for the treatment of AD.

The pathological mechanisms and novel therapeutics for Leber's hereditary optic neuropathy.

Optic neuropathies were estimated to affect 115 in 100,000 population in 2018. Leber's Hereditary Optic Neuropathy (LHON) as one of such optic neuropathy diseases that was first identified in 1871 and can be defined as a hereditary mitochondrial disease. LHON is associated with three mtDNA point mutations which are G11778A, T14484, and G3460A that affect the NADH dehydrogenase subunits of 4, 6, and 1, respectively. However, in most cases, only one point mutation is involved. Generally, in manifestation of the disease, there are no symptoms until the terminal dysfunction in the optic nerve is observed. Due to the mutations, nicotinamide adenine dinucleotide (NADH) dehydrogenase or complex I is absent and thus ATP production is stopped. This further causes the generation of reactive oxygen species and retina ganglion cells apoptosis. Aside from the mutations, there are several environmental factors such as smoking and alcohol consumption that can be pointed out as the risk factors of LHON. Nowadays, gene therapy has been intensively studied for LHON treatment. Disease models using human induced pluripotent stem cells (hiPSCs) have been utilized for LHON research.

Loss of the receptors ER, PR and HER2 promotes USP15-dependent stabilization of PARP1 in triple-negative breast cancer.

Poly(ADP-ribose) polymerase 1 (PARP1) is essential for the progression of several types of cancers. However, whether and how PARP1 is stabilized to promote genomic stability in triple-negative breast cancer (TNBC) remains unknown. Here, we demonstrated that the deubiquitinase USP15 interacts with and deubiquitinates PARP1 to promote its stability, thereby stimulating DNA repair, genomic stability and TNBC cell proliferation. Two PARP1 mutations found in individuals with breast cancer (E90K and S104R) enhanced the PARP1-USP15 interaction and suppressed PARP1 ubiquitination, thereby elevating the protein level of PARP1. Importantly, we found that estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) inhibited USP15-mediated PARP1 stabilization through different mechanisms. ER bound to the USP15 promoter to suppress its expression, PR suppressed the deubiquitinase activity of USP15, and HER2 abrogated the PARP1-USP15 interaction. The specific absence of these three receptors in TNBC results in high PARP1 levels, leading to increases in base excision repair and female TNBC cell survival.

Identification of Cutibacterium modestum in Spondylitis by Metagenomics Analysis.

BACKGROUND/AIM: Identifying pathogens with culture-negative pyogenic spondylitis is difficult. Shotgun metagenomic sequencing is an unbiased and culture-free approach in the diagnosis of infectious diseases. There are, however, a variety of contaminating factors that can confound the precision of metagenomic sequencing. CASE REPORT: In a 65-year-old man suffering from culture-negative L3-5 spondylitis, metagenomics was applied to facilitate the diagnosis. The patient underwent percutaneous endoscopic lumbar discectomy. We applied metagenomic sequencing with a robust contamination-free protocol to the bone biopsy. By comparing the abundance for each taxon between the replicates and negative controls, we reliably identified Cutibacterium modestum as having a statistically higher abundance in all replicates. The patient's antibiotic therapy was switched to penicillin and doxycycline based upon the resistome analysis; the patient fully recovered. CONCLUSION: This application of next-generation sequencing provides a new perspective in the clinical approach to spinal osteomyelitis and illustrates the potential of this technique in rapid etiological diagnosis.

Engineering near-infrared laser-activated gold nanorod vesicles with upper critical solution temperature for photothermal therapy and chemotherapy.

Multimodal synergistic therapy based on nanomedicine drug delivery systems can achieve accurate cancer treatment. The anisotropy of gold nanorods (AuNRs) allows the adjustment of the longitudinal localized surface plasmon resonance absorption to the near-infrared band, which shows potential application in the field of photothermal therapy of cancer. Here, we report a new type of thermal-sensitive gold nanorod drug-loaded vesicles (UGRV-DOX) via the self-assembly of AuNRs modified with the amphiphilic polymer (PEG45-b-PS150) and upper critical solution temperature (UCST) polymer (P(AAm-co-AN)). The hollow structure of the vesicle can increase the drug loading capacity, and the polymers on its surface are intertwined to reduce drug leakage. As-prepared UGRV-DOX vesicles exhibits excellent photothermal conversion efficiency and can achieve light-controlled drug release. In vivo anti-tumor experiments showed that UGRV-DOX could ablate HepG2 transplanted tumors significantly under 808 nm laser irradiation, and the inhibition rate was as high as 99.3 %. These tumor-specific nanovesicles prefigure great potentials for high-precision cancer treatment.

COL10A1-DDR2 axis promotes the progression of pancreatic cancer by regulating MEK/ERK signal transduction.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumors with a poor prognosis. Type X collagen α 1 chain (COL10A1), a member of the collagen family, is a gene associated with the progression of a variety of human tumors, but the specific function and molecular mechanism of COL10A1 in pancreatic cancer remain unclear. Our study found that COL10A1 is highly expressed in pancreatic cancer cells and tissues, and its high expression is related to poor prognosis and some clinicopathological features, such as tumor size and differentiation. Biological functional experiments showed that overexpression of COL10A1 enhanced the proliferation and migration of PDAC cells. Interestingly, discoid protein domain receptor 2 (DDR2), the receptor of COL10A1, is regulated by COL10A1. We found that the COL10A1-DDR2 axis activates the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, which leads to epithelial-mesenchymal transformation (EMT) and accelerates the progression of pancreatic cancer. In summary, COL10A1 regulates PDAC cell proliferation and MEK/ERK signaling pathways by binding to DDR2 to promote migration, invasion and EMT. Our study suggested that COL10A1 might be a critical factor in promoting PDAC progression. More research is needed to confirm COL10A1 as a potential biomarker and therapeutic target for PDAC.

Modified gingivoplasty for hereditary gingival fibromatosis: two case reports.

BACKGROUND: Hereditary gingival fibromatosis (HGF) is characterized by sub-epithelial fibromatosis of keratinized gingiva resulting in a fibrotic enlargement of keratinized gingiva. The treatment choice is gingivectomy, which can be performed with an internal or external bevel incision conventionally. However, both techniques can hardly resume the natural status of gingiva, and have a certain recurrence rate, especially in the cases which have limited width of attached gingiva. CASE DESCRIPTION: Two cases of HGF with the chief complaint of difficulty in mastication, pronunciation, and poor esthetics were presented. After the initial periodontal therapy, a novel gingivoplasty modified with a crevicular incision was applied. A full thickness flap above the mucogingival junction and a split flap below the junction were raised. Then, fibrotic connective tissue was completely eliminated and keratinized gingival epithelium was preserved. The fibrotic alveolar bone was shaped by handpiece and bur. Finally, the flap was apically repositioned and sutured. Twelve months after surgery, the gingiva recovered with normal color, contour and consistency. CONCLUSIONS: Compared to traditional gingivectomy, modified gingivoplasty which focuses on eliminating pathological fibrotic connective tissue can completely resume the natural appearance of gingiva and demonstrate no tendency of recurrence.

Posterior Lumbar Plexus Block Anesthesia for Elderly Patients with Lower Limb Fracture.

The incidence rate of lower limb fractures is high and has increased over the recent years, which affects the physical and mental health and the daily activities of patients. Lower limb fractures are often treated surgically. Therefore, an effective anesthesia regimen is crucial for a smooth and stable operation. To investigate the efficacy of posterior lumbar plexus block anesthesia during surgery for elderly patients with lower extremity fractures. In total, patients were divided into study and control groups. Anesthesia was administered by posterior lumbar plexus nerve block in the study group and epidural anesthesia in the control group. Hemodynamic parameters, anesthesia condition, pain level (VAS), and adverse effects were measured in both groups before anesthesia (T0), at anesthesia induction (T1), 30 min into the operation (T2), and at the end of the operation (T3). At T0, there were no significant differences in MAP and HR between the study and control groups. However, MAP and HR in the study group were significantly lower than those in the control group at T1, T2, and T3. The BIS value of the study group at each time point after anesthesia was significantly lower than that of the control group. The onset and induction time of anesthesia in the study group were also significantly shorter than those in the control group. Preoperative VAS scores did not differ between the study and control groups. However, the VAS scores of the study group at each time point were significantly lower than those of the control group. There was no significant difference in the incidence of adverse reactions between the two groups. Our results suggest that anesthesia with posterior lumbar plexus block surgery for lower extremity fractures in elderly patients can maintain hemodynamic stability and reduce block onset time, anesthesia induction time, and pain.

Analysis of trends in testicular atrophy index values with age in patients with unilateral palpable cryptorchidism.

Cryptorchidism affects the growth of testicular volume. Testicular volume is associated with reproductive function. The testicular atrophy index evaluates the degree of damage caused by cryptorchidism, but it remains unclear whether changes in testicular atrophy index are related to age. We selected patients who underwent surgery for unilateral palpable cryptorchidism. Testicular volume was measured using ultrasonography. The testicular atrophy indices of the undescended testes were then reviewed, and their correlation with age was analyzed. We studied 228 cases (age range: 6-53 months). Scatter plots were constructed, and Loess curves were fitted, revealing a turning point at 24 months of age. The patients were divided into age groups of 6-24 months and 25-53 months. The testicular volume of the cryptorchid side was smaller than that of the normal side in both groups (both P < 0.001). In the 6-24-month group, the testicular atrophy index was positively correlated with age, testicular volume on the cryptorchid side was not correlated with age, and testicular volume was positively correlated with age on the normal side. In the 25-53-month group, testicular atrophy index and testicular volumes on either side were not correlated with age. A palpable unilateral cryptorchid testis is smaller than the contralateral testis. The testicular atrophy index increases with age between 6 months and 24 months, but not between 25 months and 53 months. Testicular volume increased with age on the normal side between 6 months and 24 months, but not on the cryptorchid side. Trends in testicular atrophy index with age contribute to the decision of operation time.

Fabrication and characterization of soy ß-conglycinin-dextran-polyphenol nanocomplexes: Improvement on the antioxidant activity and sustained-release property of curcumin.

In this study, glycated soy ß-conglycinin (ß-CG) stabilized curcumin (Cur) composites were fabricated by a unique reversible self-assembly character of ß-conglycinin-dextran conjugates (ß-CG-DEX). Intrinsic fluorescence and far-UV CD spectra revealed that glycation did not affect the self-assembly property of ß-CG in the pH-shifting treatment. The structure of ß-CG-DEX could be unfolded at pH 12.0 and reassembled during acidification (from pH 12.0 to 7.0). Meanwhile, ß-CG-DEX-3d, which was incubated at 60 °C for 3 days, exhibited a high loading capacity (123.4 mg/g) for curcumin, which far exceeds that (74.90 mg/g) of ß-CG-Cur. Moreover, the reassembled ß-CG-DEX-3d-Cur showed eminent antioxidant activity of approximately 1.5 times higher than that of free curcumin. During the simulated gastrointestinal condition, compared with ß-CG-Cur, ß-CG-DEX-3d-Cur nanoparticles showed a more stable and sustained release of curcumin. Thus, ß-CG-DEX has immense potential to become a new delivery carrier for hydrophobic food components by means of a self-assembly strategy.

Combined Microbiome and Metabolome Analysis Reveals a Novel Interplay Between Intestinal Flora and Serum Metabolites in Lung Cancer.

As the leading cause of cancer death, lung cancer seriously endangers human health and quality of life. Although many studies have reported the intestinal microbial composition of lung cancer, little is known about the interplay between intestinal microbiome and metabolites and how they affect the development of lung cancer. Herein, we combined 16S ribosomal RNA (rRNA) gene sequencing and liquid chromatography-mass spectrometry (LC-MS) technology to analyze intestinal microbiota composition and serum metabolism profile in a cohort of 30 lung cancer patients with different stages and 15 healthy individuals. Compared with healthy people, we found that the structure of intestinal microbiota in lung cancer patients had changed significantly (Adonis, p = 0.021). In order to determine how intestinal flora affects the occurrence and development of lung cancer, the Spearman rank correlation test was used to find the connection between differential microorganisms and differential metabolites. It was found that as thez disease progressed, L-valine decreased. Correspondingly, the abundance of Lachnospiraceae_UCG-006, the genus with the strongest association with L-valine, also decreased in lung cancer groups. Correlation analysis showed that the gut microbiome and serum metabolic profile had a strong synergy, and Lachnospiraceae_UCG-006 was closely related to L-valine. In summary, this study described the characteristics of intestinal flora and serum metabolic profiles of lung cancer patients with different stages. It revealed that lung cancer may be the result of the mutual regulation of L-valine and Lachnospiraceae_UCG-006 through the aminoacyl-tRNA biosynthesis pathway, and proposed that L-valine may be a potential marker for the diagnosis of lung cancer.

Comparison of the Curative Efficacy of Hemivertebra Resection via the Posterior Approach Assisted With Unilateral and Bilateral Internal Fixation in the Treatment of Congenital Scoliosis.

Objective: This study aimed to compare the curative efficacy of hemivertebra resection via the posterior approach assisted with unilateral and bilateral internal fixation in the treatment of congenital scoliosis (CS). Methods: In this study, 29 children (15 males and 14 females), who underwent hemivertebra resection via the posterior approach and received internal fixation from November 2005 to September 2018, were analyzed retrospectively. The age of these patients ranged from 0.9 to 15 years, with an average of 3.8 years. The follow-up duration ranged from 2 to 12.3 years, with an average of 5.7 years. The patients in group A received unilateral internal fixation, and those in group B received bilateral internal fixation. The operation duration, bleeding volume, and complications during the operation, as well as the Cobb angles of scoliosis and kyphosis before and after the operation and at the last follow-up, were compared between the two groups. Results: In group A, the operation duration was 207.4 ± 54.5 min, and the bleeding volume was 215.3 ± 75.4 ml; in group B, the operation duration was 249.5 ± 51.0 min, and the bleeding volume was 291.3 ± 115.6 ml (P < 0.05). The Cobb angles of segmental scoliosis, segmental kyphosis, cephalic compensatory curve, and caudal compensatory curve were significantly improved in the two groups after operation and at the last follow-up (P < 0.05). The post-operative correction rate of the scoliosis Cobb angle was 67.2% in group A and 79.5% in group B; and the difference was statistically significant (P < 0.05). At the last follow-up, the correction rate of the scoliosis Cobb angle was 72.7% in group A and 76.2% in group B (P > 0.05). After the operation and at the last follow-up, the correction rates of kyphosis were 83.1 and 79.6% in group A and 71.8 and 65.5% in group B (P > 0.05). Conclusion: Hemivertebra resection via posterior approach with unilateral internal fixation can also achieve the effect of bilateral internal fixation in the treatment of CS. It is able to preserve a certain degree of contralateral spinal growth potential and is a feasible method.

Identification of Key Drug Targets and Molecular Mechanisms of Curcumae Rhizoma Acting on HBV-Related HCC: Weighted Correlation Network and Network Pharmacological Analyses.

Background: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has poor prognosis and high mortality rate. Curcumae Rhizoma, a classic Chinese medicinal herb, is often used to treat tumors. Methods: Active ingredients of Curcumae Rhizoma were extracted from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) database, and potential targets were predicted by the TCMSP database and Swiss Target Prediction database. The key drug targets were filtered by intersecting predicted targets, DEGs, and genes in important modules from WGCNA. Besides, the key drug targets were used to construct a network of "herb-active ingredient-target-disease" interactions and subjected to enrichment analysis and protein-protein interaction (PPI) analysis. The hub targets based on PPI analysis was evaluated by the KMplotter database. Results: Three active ingredients of Curcumae Rhizoma were collected with OB ≥ 30% and DL ≥ 0.18, including hederagenin, wenjine, and bisdemethoxycurcumin. The key drug targets were mainly enriched in cell cycle checkpoint, DNA integrity checkpoint, and peptidyl-serine modification. Besides, Curcumae Rhizoma treatment of HBV-related HCC mainly involved the p53 signaling pathway and arachidonic acid metabolism. Finally, ESR1 and PTGS2 were identified as hub targets from PPI analysis. ESR1 was found to be correlated with survival in liver cancer patients with hepatitis. Conclusion: Based on WGCNA and network pharmacological analysis, our results illustrated that Curcumae Rhizoma might work through regulating multitargets and multipathways in HBV-related HCC.

Amitosis as a strategy of cell division-Insight from the proliferation of Tetrahymena thermophila macronuclei.

Cell division is a necessity of life which can be either mitotic or amitotic. While both are fundamental, amitosis is sometimes considered a relic of little importance in biology. Nevertheless, eukaryotes often have polyploid cells, including cancer cells, which may divide amitotically. To understand how amitosis ensures the completion of cell division, we turn to the macronuclei of ciliates. The grand scheme governing the proliferation of the macronuclei of ciliate cells, which involves chromosomal replication and amitosis, is currently unknown, which is crucial for developing population genetics model of ciliate populations. Using a novel model that encompasses a wide range of mechanisms together with experimental data of the composition of mating types at different stages derived from a single karyonide of Tetrahymena thermophila, we show that the chromosomal replication of the macronucleus has a strong head-start effect, with only about five copies of chromosomes replicated at a time and persistent reuse of the chromosomes involved in the early replication. Furthermore the fission of a fully grown macronucleus is non-random with regard to chromosome composition, with a strong tendency to push chromosomes and their replications to the same daughter cell.

Ferritinophagy-Mediated Ferroptosis and Activation of Keap1/Nrf2/HO-1 Pathway Were Conducive to EMT Inhibition of Gastric Cancer Cells in Action of 2,2'-Di-pyridineketone Hydrazone Dithiocarbamate Butyric Acid Ester.

In metastasis of cancer cells, the epithelial-mesenchymal transition (EMT) is prerequired. Ferroptosis is an iron-mediated cellular death process, but whether it involves EMT regulation remains elusive. In addition, how stress responders (Nrf2) respond to the redox alteration and cross-talking between them needs to be determined. Our data revealed that DpdtbA (2,2'-di-pyridineketone hydrazone dithiocarbamate butyric acid ester) resisted TGF-ß1-induced EMT in gastric cancer lines (SGC-7901 and MGC-823) through ferritinophagy-mediated ROS production. Furthermore, the depletion of Gpx4 and xCT as well as enhanced lipid peroxidation indicated that DpdtbA acted as Erastin did in ferroptosis induction, which thus provided chance to explore the causal relationship between ferroptosis and EMT. Our data illustrated that ferritinophagy-mediated ferroptosis promoted the EMT inhibition. In addition, activated Nrf2 involved the regulation on both ferroptosis and EMT in response to the alteration in the cellular redox environment. In brief, ferritinophagy-mediated ferroptosis and activation of the Keap1/Nrf2/HO-1 pathway were conducive to the EMT inhibition.