bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-cancer effect of palmatine through inhibition of the PI3K/AKT pathway in canine mammary gland tumor CMT-U27 cells
Authors: Yoo Min-Jae , Choi Jawun , Jang Ye-ji , Park Sang-Youel , Seol Jae-Won
Published: October 2023

Canine mammary gland tumors (CMTs) are the most common and lethal cancers in female dogs. Dysregulated phosphoinositide 3-kinases (PI3K)/AKT pathway reportedly was involved in the growth and metastasis of CMTs. However, there are few studies on therapeutic strategies for targeting the PI3K pathway in CMTs. In this study, we aimed to determine whether palmatine, a natural isoquinoline alkaloid with anti-cancer properties, could inhibit the growth of CMTs and whether the inhibitory effect was mediated through the PI3K/AKT pathway. Our in vitro experiments on CMT-U27, a CMT cell line, showed that palmatine reduced cell proliferation and induced cell death. Western blotting results revealed that palmatine decreased the protein expression of PI3K, PTEN, AKT, and mechanistic target of rapamycin in the PI3K/AKT pathway, which was supported by the results of immunocytochemistry. Additionally, palmatine suppressed the migration and tube formation of canine aortic endothelial cells as well as the migration of CMT U27 cells. Our in vivo results showed that palmatine inhibited tumor growth in a CMT-U27 mouse xenograft model. We observed a decreased expression of proteins in the PI3K/AKT pathway in tumor tissues, similar to the in vitro results. Furthermore, palmatine significantly disrupted the tumor vasculature and inhibited metastasis to adjacent lymph nodes. In conclusion, our findings demonstrate that palmatine exerts anti-cancer effects against CMTs by inhibiting PI3K/AKT signaling pathway, suggesting that palmatine has potential as a canine-specific PI3K inhibitor for the treatment of CMTs.
Identification of the role of endoplasmic reticulum stress genes in endometrial cancer and their association with tumor immunity
Authors: Zhang Tang ansu , Zhang Qian , Zhang Jun , Zhao Rong , Shi Rui , Wei Sitian , Liu Shuangge , Zhang Qi , Wang Hongbo
Published: October 2023

Background

Endometrial cancer (EC) is one of the worldwide gynecological malignancies. Endoplasmic reticulum (ER) stress is the cellular homeostasis disturbance that participates in cancer progression. However, the mechanisms of ER Stress on EC have not been fully elucidated.

Method

The ER Stress-related genes were obtained from Gene Set Enrichment Analysis (GSEA) and GeneCards, and the RNA-seq and clinical data were downloaded from The Cancer Genome Atlas (TCGA). The risk signature was constructed by the Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis. The significance of the risk signature and clinical factors were tested by time-dependent receiver operating characteristic (ROC) curves, and the selected were to build a nomogram. The immunity correlation was particularly analyzed, including the related immune cells, pathways, and immune checkpoints. Functional enrichment, potential chemotherapies, and in vitro validation were also conducted.

Result

An ER Stress-based risk signature, consisting of TRIB3, CREB3L3, XBP1, and PPP1R15A was established. Patients were randomly divided into training and testing groups with 1:1 ratio for subsequent calculation and validation. Based on risk scores, high- and low-risk subgroups were classified, and low-risk subgroup demonstrated better prognosis. The Area Under Curve (AUC) demonstrated a reliable predictive capability of the risk signature. The majority of significantly different immune cells and pathways were enriched more in low-risk subgroup. Similarly, several typical immune checkpoints, expressed higher in low-risk subgroup. Patients of the two subgroups responded differently to chemotherapies.

Conclusion

We established an ER Stress-based risk signature that could effectively predict EC patients’ prognosis and their immune correlation.
Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway
Authors: Zhang Ning , Liu Zhouzhong , Lai Xuwang , Liu Shubin , Wang Yuli
Published: October 2023

Objective

CD147 is an important glycoprotein that participates in the progression of diverse cancers. This study aims to explore the specific function of CD147 in lung adenocarcinoma (LUAD) and to reveal related downstream molecular mechanisms.

Methods

Followed by silencing of CD147, the viability, migration, invasion, and apoptosis of LUAD cells were measured by CCK8, wound healing, transwell assay, and flow cytometer, respectively. The expression of CD147 and two markers of lipid metabolism (FASN and ACOX1) were detected by qRT-PCR. A xenograft tumor model was constructed to investigate the function of CD147 in vivo. Then transcriptome sequencing was performed to explore the potential mechanisms. After measuring the expression of Rap1 and p-p38 MAPK/p38 MAPK by western blot, the changes of CD147 and lipid metabolism markers (FASN, ACOX1) was detected by Immunohistochemistry. Moreover, a Rap1 activator and a Rap1 inhibitor were applied for feedback functional experiments.

Results

CD147 was up-regulated in LUAD cells, and its silencing inhibited cell proliferation, migration, invasion, lipid metabolism dysregulation and promoted apoptosis, while overexpression of CD147 showed the opposite results. Silencing of CD147 also inhibited the growth of tumor xenografts in mice. Transcriptome sequencing revealed 834 up-regulated differentially expressed genes (DEGs) and 602 down-regulated DEGs. After functional enrichment, the Rap1 signaling pathway was selected as a potential target, which was then verified to be blocked by CD147 silencing. In addition, the treatment of Rap1 activator weakened the inhibiting effects of si-CD147 on the proliferation, migration, invasion, and lipid metabolism in LUAD cells, while the intervention of RAP1 inhibitor showed the opposite results.

Conclusions

Silencing of CD147 inhibited the proliferation, migration, invasion, lipid metabolism dysregulation and promoted apoptosis of LUAD cells through blocking the Rap1 signaling pathway.
Systematic engineering pinpoints a versatile strategy for the expression of functional cytochrome P450 enzymes in Escherichia coli cell factories
Authors: Poborsky Michal , Crocoll Christoph , Motawie Mohammed Saddik , Halkier Barbara Ann
Published: October 2023

Production of plant secondary metabolites in engineered microorganisms provides a scalable and sustainable alternative to their sourcing from nature or through chemical synthesis. However, the biosynthesis of many valuable plant-derived products relies on cytochromes P450 – enzymes notoriously difficult to express in microbes. To improve their expression in Escherichia coli, an arsenal of engineering strategies was developed, often paired with an extensive screening of enzyme variants. Here, attempting to identify a broadly applicable strategy, we systematically evaluated six common cytochrome P450 N-terminal modifications and their effect on in vivo activity of enzymes from the CYP79 and CYP83 families. We found that transmembrane domain truncation was the only modification with a significantly positive effect for all seven tested enzymes, increasing their product titres by 2- to 170-fold. Furthermore, when comparing the changes in the protein titre and product generation, we show that higher protein expression does not directly translate to higher in vivo activity, thus making the protein titre an unreliable screening target in the context of cell factories. We propose the transmembrane domain truncation as a first-line approach that enables the expression of wide range of highly active P450 enzymes in E. coli and circumvents the time-consuming screening process. Our results challenge the notion that the engineering strategy must be tailored for each individual cytochrome P450 enzyme and have the potential to simplify and accelerate the future design of E. coli cell factories.
The role of oncolytic virotherapy and viral oncogenes in the cancer stem cells: a review of virus in cancer stem cells
Authors: Faghihkhorasani Amirhosein , Dalvand Alaleh , Derafsh Ehsan , Tavakoli Farnaz , Younis Nada Khairi , Yasamineh Saman , Gholizadeh Omid , Shokri Pooria
Published: October 2023

Cancer Stem Cells (CSCs) are the main “seeds” for the initiation, growth, metastasis, and recurrence of tumors. According to many studies, several viral infections, including the human papillomaviruses, hepatitis B virus, Epstein–Barr virus, and hepatitis C virus, promote the aggressiveness of cancer by encouraging the development of CSC features. Therefore, a better method for the targeted elimination of CSCs and knowledge of their regulatory mechanisms in human carcinogenesis may lead to the development of a future tool for the management and treatment of cancer. Oncolytic viruses (OVs), which include the herpes virus, adenovirus, vaccinia, and reovirus, are also a new class of cancer therapeutics that have favorable properties such as selective replication in tumor cells, delivery of numerous eukaryotic transgene payloads, induction of immunogenic cell death and promotion of antitumor immunity, as well as a tolerable safety profile that essentially differs from that of other cancer therapeutics. The effects of viral infection on the development of CSCs and the suppression of CSCs by OV therapy were examined in this paper. The purpose of this review is to investigate the dual role of viruses in CSCs (oncolytic virotherapy and viral oncogenes).

Graphical Abstract
Assessing IRS performance in a gender-integrated vector control programme on Bioko Island, Equatorial Guinea, 2010–2021
Authors: DeBoer Kylie R. , Vaz Liberato Motobe , Ondo Mfumu Teresa Ayingono , Nlang Jose Antonio Mba , Ondo Lucas , Riloha Rivas Matilde , Incardona Sandra , Pollock John , von Fricken Michael E. , Mba Eyono Jeremías Nzamio , Donfack Olivier T. , Guerra Carlos A. , García Guillermo A.
Published: October 2023

Background

Indoor residual spraying (IRS) is a common vector control strategy in countries with high malaria burden. Historically, social norms have prevented women from working in IRS programmes. The Bioko Island Malaria Elimination Project has actively sought to reduce gender inequality in malaria control operations for many years by promoting women’s participation in IRS.

Methods

This study investigated the progress of female engagement and compared spray productivity by gender from 2010 to 2021, using inferential tests and multivariable regression. Spray productivity was measured by rooms sprayed by spray operator per day (RSOD), houses sprayed by spray operator per day (HSOD), and the daily productivity ratio (DPR), defined as the ratio of RSOD to HSOD, which standardized productivity by house size.

Results

The percentage of women participating in IRS has increased over time. The difference in DPR comparing male and female spray operators was only statistically significant (p < 0.05) for two rounds, where the value was higher for women compared to men. Regression analyses showed marginal, significant differences in DPR between men and women, but beta coefficients were extremely small and thus not indicative of a measurable effect of gender on operational performance.

Conclusions

The quantitative analyses of spray productivity are counter to stigmatizing beliefs that women are less capable than male counterparts during IRS spray rounds. The findings from this research support the participation of women in IRS campaigns, and a renewed effort to implement equitable policies and practices that intentionally engage women in vector control activities.
Nonlinear connection between remnant cholesterol and stroke risk: evidence from the China health and retirement longitudinal study
Authors: Wang Yuanqing , Zha Fubing , Han Yong , Cai Ying , Chen Miaoling , Yang Cui , Cai Xiaodong , Hu Haofei , Cao Changchun , Luo Jiao
Published: October 2023

Objective

The evidence on the relationship between remnant cholesterol (RC) and stroke remains controversial. Therefore, this study aimed to explore the relationship between RC and stroke risk in a Chinese population of middle-aged and elderly individuals.

Methods

The present study included 10067 Chinese subjects of middle-aged and elderly individuals. The connection between RC and incident stroke was investigated using the multivariate Cox proportional hazards regression model, several sensitivity analyses, generalized additive models, and smoothed curve fitting.

Results

A total of 1180 participants with stroke were recorded during the follow-up period. The multivariate Cox proportional hazards regression model identified a positive connection between RC and stroke risk (hazard ratio (HR) = 1.087, 95% confidence interval (CI): 1.001–1.180). In addition, the current study discovered a nonlinear connection between RC and incident stroke, and the point of inflection for RC was 1.78 mmol/L. The risk of stroke increased by 25.1% with each unit increase in RC level when RC was < 1.78 mmol/L (HR:1.251, 95%CI: 1.089–1.437, P = 0.0015). The results were not affected by sensitivity tests.

Conclusion

The current study showed a positive and nonlinear connection between RC and stroke risk in a middle-aged and elderly Chinese population. These findings provided new information to help researchers better understand the relationship between RC levels and incident stroke.
Causal inference of sex hormone-binding globulin on venous thromboembolism: evidence from Mendelian randomisation
Authors: Wang Shuping , Wang Yongxiang , Bai Ming , Peng Yu , Zhou Dan , Lei Peng , Zhou Binpeng , Zhang Piyi , Zhang Zheng
Published: October 2023

Background

Previous cohort studies have shown that exogenous sex hormone use, such as testosterone replacement therapy and oestrogen-containing contraceptives, can increase the risk of venous thromboembolism (VTE). However, the relationship between endogenous sex hormone levels and VTE remains unclear. The goal of the present study was to explore the causal roles of endogenous sex hormones, including hormone-binding globulin (SHBG), bioactive testosterone (BT), and total testosterone (TT), in VTE and its two subgroups, deep vein thrombosis (DVT) and pulmonary embolism (PE).

Methods

We used a genome-wide association study of sex hormones as exposure data and Finnish VTE data as the outcome. Inverse variance weighting, MR-Egger, and weighted median were used for two-sample Mendelian randomisation (MR). Sensitivity analyses included MR-Egger, MR-PRESSO, Cochrane Q test, MR Steiger, leave-one-out analysis, and funnel plot, combined with multivariate MR and replicated MR analyses using larger VTE data from the global biobank meta-analysis initiative. Linkage disequilibrium score regression (LDSC) was used to determine genetic associations and estimate sample overlap.

Results

Our findings genetically predicted that an increase in serum SHBG levels by one standard deviation (SD) caused 25% higher odds for VTE (OR: 1.25, 95% CI: 1.01−1.55) and 58% higher odds for PE (OR: 1.58, 95% CI: 1.20−2.08). LDSC supported the genetic correlation between these two traits and replicated analyses confirm SHBG’s genetic effect on VTE in both sexes (OR: 1.46, 95% CI: 1.20−1.78) and in females (OR: 1.49, 95% CI: 1.17−1.91). In addition, an increase in serum TT levels by one SD caused 32% higher odds for VTE (OR: 1.32, 95% CI: 1.08−1.62) and 31% higher odds for DVT (OR: 1.31, 95% CI: 1.01−1.69); however, LDSC and replicated analyses did not find a genetic correlation between TT and VTE or its subtypes. No significant correlation was observed between BT and all three outcome traits.

Conclusion

Our study provides evidence that elevated serum SHBG levels, as predicted by genetics, increase VTE risk. However, the causal effect of testosterone levels on VTE requires further investigation.
Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus
Authors: Grønning Rebecca , Jeppsson Anna , Hellström Per , Laurell Katarina , Farahmand Dan , Zetterberg Henrik , Blennow Kaj , Wikkelsø Carsten , Tullberg Mats
Published: October 2023

Introduction

The relationship between neurochemical changes and outcome after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable dementia and gait disorder, is unclear. We used baseline ventricular CSF to explore associations to outcome, after shunting, of biomarkers selected to reflect a range of pathophysiological processes.

Methods

In 119 consecutive patients with iNPH, the iNPH scale was used before and after shunt surgery to quantify outcome. Ventricular CSF was collected perioperatively and analyzed for biomarkers of astrogliosis, axonal, amyloid and tau pathology, and synaptic dysfunction: glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL40/CHI3L1), monocyte chemoattractant protein-1 (MCP-1) neurofilament light (NfL), amyloid beta 38 (Aβ38), Aβ40, Aβ42, amyloid beta 42/40 ratio (Aβ42/40), soluble amyloid precursor protein alfa (sAPPα), sAPPβ, total tau (T-tau), phosphorylated tau (P-tau), growth-associated protein 43 (GAP43), and neurogranin.

Results

The neurogranin concentration was higher in improved (68%) compared to unimproved patients (median 365 ng/L (IQR 186–544) vs 330 (205–456); p = 0.046). A linear regression model controlled for age, sex and vascular risk factors including neurogranin, T-tau, and GFAP, resulted in adjusted R2 = 0.06, p = 0.047. The Aβ42/40 ratio was bimodally distributed across all samples, as well as in the subgroups of improved and unimproved patients but did not contribute to outcome prediction. The preoperative MMSE score was lower within the low Aβ ratio group (median 25, IQR 23–28) compared to the high subgroup (26, 24–29) (p = 0.028). The T-Tau x Aβ40/42 ratio and P-tau x Aβ40/42 ratio did not contribute to shunt response prediction. The prevalence of vascular risk factors did not affect shunt response.

Discussion

A higher preoperative ventricular CSF level of neurogranin, which is a postsynaptic marker, may signal a favorable postoperative outcome. Concentrations of a panel of ventricular CSF biomarkers explained only 6% of the variability in outcome. Evidence of amyloid or tau pathology did not affect the outcome.
Patterns of use of wild food plants by Brazilian local communities: systematic review and meta-analysis
Authors: Gomes Lailson César Andrade , Medeiros Patrícia Muniz de , Prata Ana Paula do Nascimento
Published: October 2023

Background

This systematic review and meta-analysis sought to investigate the patterns of use of native wild food plants of Brazil (native and non-cultivated).

Methods

We searched ethnobiological works with food plants in Web of Science, Scielo, Scopus and PubMed using different sets of keywords. Initially, the studies were evaluated based on inclusion criteria (systematic data collection instruments, such as interviews; specification of methods for data collection; and the presence of a species list). The methodological quality of each study was evaluated to define the risk of bias. A total of 20 articles met all criteria and were included in the review.

Results

The results showed that there was a predominance of consumption of fruits, followed by leaves and seeds, which together represented 85.8% of the total parts. As for the meta-analysis, there was a predominance of use of plant parts classified as reproductive, non-persistent, non-destructive and parts of woody plants. There was no interference from the type of ecosystem (seasonally dry x moist). The results did not support the seasonality hypothesis.

Conclusions

The concentration of studies in the Northeast, Southeast and South regions of Brazil and in the Atlantic Forest and Caatinga biomes points to the need for a greater effort in terms of quantitative ethnobotanical research in other regions and biomes. The predominance of fruits and plant parts classified as reproductive, non-persistent and non-destructive points to the high potential for implementation of sustainable management strategies aimed at these plants in the country.
Evaluation of the serum tRNA-derived fragment tRF-5022B as a potential biomarker for the diagnosis of osteoarthritis
Authors: Ni Yingchen , Wu Anqi , Li Jianxin , Zhang Weidong , Wang Youhua
Published: October 2023

Osteoarthritis (OA) is a degenerative disease. It is common in middle-aged and elderly people and is one of the main causes of disability. Currently, the etiology of OA is unclear, and no specific biomarkers for the diagnosis of OA have been identified. Therefore, finding a highly sensitive biomarker is essential for a proper diagnosis.

TRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs) are newly discovered classes of noncoding RNAs. tRF has been proven in several studies to have significant associations with tumor diagnosis, making it a promising biomarker in cancer research. However, the diagnostic utility of tRF in OA patients and the correlation between OA progression and trf differential expression have yet to be elaborated. The purpose of this research was to identify tRFs with differential expression in OA to assess their potential as OA biomarkers. To determine the tRF-5022B expression level in this research, real-time fluorescence quantitative PCR has been employed. Agarose gel electrophoresis, Sanger sequencing, and other investigations have been employed for evaluating tRF-5022B's molecular properties. Receiver operating characteristic curve analysis has been utilized for assessing the diagnostic effectiveness of the tRF-5022B. The findings demonstrated that tRF-5022B expression was considerably lower in OA serum. The Kellgren–Lawrence grading scale was shown to correspond with serum expression levels. The ROC curve confirmed that tRF-5022B serum expression levels might differentiate OA cases from healthy individuals and RA patients. According to the aforementioned findings, tRF-5022B may be employed as a novel biomarker for OA diagnosis due to its excellent diagnostic value.
Autocrine regulation of tumor cell repopulation by Hsp70-HMGB1 alarmin complex
Authors: Sverchinsky Dmitry V. , Alhasan Bashar A. , Mikeladze Marina A. , Lazarev Vladimir F. , Kuznetcova Liubov S. , Morshneva Alisa V. , Nikotina Alina D. , Ziewanah Amr , Koludarova Lidia V. , Starkova Tatiana Y. , Margulis Boris A. , Guzhova Irina V.
Published: October 2023

Background

Cancer recurrence is regulated by a variety of factors, among which is the material of dying tumor cells; it is suggested that remaining after anti-cancer therapy tumor cells receive a signal from proteins called damage-associated molecular patterns (DAMPs), one of which is heat shock protein 70 (Hsp70).

Methods

Two models of tumor repopulation were employed, based on minimal population of cancer cells and application of conditioned medium (CM). To deplete the CMs of Hsp70 affinity chromatography on ATP-agarose and immunoprecipitation were used. Cell proliferation and the dynamics of cell growth were measured using MTT assay and xCELLigence technology; cell growth markers were estimated using qPCR and with the aid of ELISA for prostaglandin E detection. Immunoprecipitation followed by mass-spectrometry was employed to identify Hsp70-binding proteins and protein-protein interaction assays were developed to reveal the above protein complexes.

Results

It was found that CM of dying tumor cells contains tumor regrowth-initiating factors and the removal of one of them, Hsp70, caused a reduction in the relapse-activating capacity. The pull out of Hsp70 alone using ATP-agarose had no effect on repopulation, while the immunodepletion of Hsp70 dramatically reduced its repopulation activity. Using proteomic and immunochemical approaches, we showed that Hsp70 in conditioned medium binds and binds another abundant alarmin, the High Mobility Group B1 (HMGB1) protein; the complex is formed in tumor cells treated with anti-cancer drugs, persists in the cytosol and is further released from dying tumor cells. Recurrence-activating power of Hsp70-HMGB1 complex was proved by the enhanced expression of proliferation markers, Ki67, Aurka and MCM-10 as well as by increase of prostaglandin E production and autophagy activation. Accordingly, dissociating the complex with Hsp70 chaperone inhibitors significantly inhibited the pro-growth effects of the above complex, in both in vitro and in vivo tumor relapse models.

Conclusions

These data led us to suggest that the abundance of the Hsp70-HMGB1 complex in the extracellular matrix may serve as a novel marker of relapse state in cancer patients, while specific targeting of the complex may be promising in the treatment of cancers with a high risk of recurrence.
Antibody drug conjugates: hitting the mark in pancreatic cancer?
Authors: Wittwer Nicole L. , Brown Michael P. , Liapis Vasilios , Staudacher Alexander H.
Published: October 2023

Pancreatic cancer is one of the most common causes of cancer-related death, and the 5-year survival rate has only improved marginally over the last decade. Late detection of the disease means that in most cases the disease has advanced locally and/or metastasized, and curative surgery is not possible. Chemotherapy is still the first-line treatment however, this has only had a modest impact in improving survival, with associated toxicities. Therefore, there is an urgent need for targeted approaches to better treat pancreatic cancer, while minimizing treatment-induced side-effects. Antibody drug conjugates (ADCs) are one treatment option that could fill this gap. Here, a monoclonal antibody is used to deliver extremely potent drugs directly to the tumor site to improve on-target killing while reducing off-target toxicity. In this paper, we review the current literature for ADC targets that have been examined in vivo for treating pancreatic cancer, summarize current and on-going clinical trials using ADCs to treat pancreatic cancer and discuss potential strategies to improve their therapeutic window.
The inhibitory effect of Gremlin-2 on adipogenesis suppresses breast cancer cell growth and metastasis
Authors: Jung Jiwoo , Kim Na Hui , Kwon Minji , Park Jayeon , Lim Dayeon , Kim Youjin , Gil World , Cheong Ye Hwang , Park Sin-Aye
Published: October 2023

Background

Gremlin-1 (GREM1) and Gremlin-2 (GREM2) are bone morphogenetic protein antagonists that play important roles in organogenesis, tissue differentiation, and tissue homeostasis. Although GREM1 has been reported to be involved in promoting various cancers, little has been reported about effects of GREM2 on cancer. Recently, it has been reported that GREM2 can inhibit adipogenesis in adipose-derived stromal/stem cells. However, as an inhibitor of adipogenesis, the role of GREM2 in cancer progression is not well understood yet.

Methods

Pre-adipocyte 3T3-L1 cells overexpressing mock or Grem2 were established using a lentiviral transduction system and differentiated into adipocytes-mock and adipocytes-Grem2, respectively. To investigate the effect of adipocyte-Grem2 on breast cancer cells, we analyzed the proliferative and invasion abilities of spheroids using a 3D co-culture system of breast cancer cells and adipocytes or conditioned medium (CM) of adipocytes. An orthotopic breast cancer mouse model was used to examine the role of adipocytes-Grem2 in breast cancer progression.

Results

Grem2 overexpression suppressed adipogenesis of 3T3-L1 cells. Proliferative and invasion abilities of spheroids formed by co-culturing MTV/TM-011 breast cancer cells and adipocytes-Grem2 were significantly reduced compared to those of spheroids formed by co-culturing MTV/TM-011 cells and adipocytes-mock. Compared to adipocytes-mock, adipocytes-Grem2 showed decreased mRNA expression of several adipokines, notably IL-6. The concentration of IL-6 in the CM of these cells was also decreased. Proliferative and invasive abilities of breast cancer cells reduced by adipocytes-Grem2 were restored by IL-6 treatment. Expression levels of vimentin, slug, and twist1 in breast cancer cells were decreased by treatment with CM of adipocytes-Grem2 but increased by IL-6 treatment. In orthotopic breast cancer mouse model, mice injected with both MTV/TM-011 cells and adipocytes-Grem2 showed smaller primary tumors and lower lung metastasis than controls. However, IL-6 administration increased both the size of primary tumor and the number of metastatic lung lesions, which were reduced by adipocytes-Grem2.

Conclusions

Our study suggests that GREM2 overexpression in adipocytes can inhibit adipogenesis, reduce the expression and secretion of several adipokines, including IL-6, and ultimately inhibit breast cancer progression.
Cercopithifilaria spp. of dogs: little known but prevalent filarioids beneath the skin
Authors: Bezerra-Santos Marcos Antonio , Dantas-Torres Filipe , Ramos Rafael Antonio Nascimento , Brianti Emanuele , Otranto Domenico
Published: October 2023

Filarioids of the genus Cercopithifilaria are little studied, yet widespread parasites, that are relatively unique in being one of the very few nematodes transmitted by hard ticks. These filarioids live in the subcutis while microfilariae are found in the dermis. Definitive hosts include domestic dogs as well as a wide range of vertebrates, such as ruminants, non-human primates, murids, marsupials, porcupines, viverrids, bears and lagomorphs. The genus Cercopithifilaria contains three taxa (i.e. C. bainae, C. grassii and a yet undescribed species, namely Cercopithifilaria sp. II) that are known to infect dogs worldwide, with their occurrence overlapping the distribution of the main tick vector, Rhipicephalus sanguineus sensu lato. In recent decades, more attention has focused on these filarioids since they have been associated with clinical signs of infection, such as dermatitis, chronic polyarthritis and cutaneous cysts, and possibly with facilitating infections caused by other tick-borne pathogens. Nevertheless, these parasites remain largely underdiagnosed in clinical practice due to the lack of awareness of veterinary practitioners and to major obstacles to their diagnosis. In this review, we have assessed currently available data on Cercopithifilaria spp. infecting dogs worldwide and discussed the biological, clinical and epidemiological aspects of these filarioids, with the overall aim to gain a better understanding of their potential role in skin diseases.

Graphical abstract
Contrast media extravasation injury: a prospective observational cohort study
Authors: Liu Wanli , Wang Pinghu , Zhu Hui , Tang Hui , Guan Hongmei , Wang Xiaoying , Wang Chengxiang , Qiu Yao , He Lianxiang
Published: October 2023

Objective

To identify the risk factors for moderate and severe contrast media extravasation and provide effective guidance to reduce the degree of extravasation injuries.

Methods

We observed 224 adult patients who underwent contrast media extravasation at Xiangya Hospital of Central South University, Hunan Provincial Maternal and Child Healthcare Hospital, and Xiangya Changde Hospital, Hunan Province between January 1, 2018 and December 31, 2022. Risk factors for moderate extravasation injuries were evaluated using univariate and multivariate logistic regression.

Results

Among 224 patients, 0 (0%) had severe, 18 (8.0%) had moderate, and 206 (92.0%) had mild contrast media extravasation injury. Multivariate logistic regression analysis revealed malignant tumors (odds ratio [OR] = 6.992, 95% confidence interval [CI]: 1.674–29.208), Iohexol (OR = 9.343, 95% CI 1.280–68.214), large-volume (> 50 mL) extravasation (OR = 5.773, 95% CI 1.350‒24.695), and injection site (back of the hand) (OR = 13.491, 95% CI 3.056–59.560) as independent risk factors for moderate injury.

Conclusion

Risk factors for moderate contrast media extravasation injury are malignant tumors, iohexol, large-volume (> 50 mL) extravasation, and back-of-the-hand injection. Analysis of these risk factors can help reduce the degree of injury after extravasation.

Clinical relevance statement

High-risk patients with extravasation support should choose the appropriate contrast media type, avoiding back-of-the-hand injections. We recommend that patients with cancer be implanted with a high-pressure resistant central venous catheter and receive effective measures to timely detect and reduce extravasation.
Ethnicity as a risk factor for gambling disorder: a large-scale study linking data from the Norwegian patient registry with the Norwegian social insurance database
Authors: Aarestad Sarah Helene , Erevik Eilin Kristine , Smith Otto Robert Frans , Griffiths Mark D. , Leino Tony Mathias , Mentzoni Rune Aune , Pallesen Ståle
Published: October 2023

Background

The study investigated ethnicity as a risk factor for gambling disorder (GD), controlling for demographics, citizenship, and years of residency in Norway.

Methods

The sample comprised 65,771 individuals from a national patient registry (n = 35,607, age range 18–88 years) and a national social insurance database in Norway (n = 30,164, age rage 18–98 years). The data covered the period from 2008 to 2018.

Results

The results showed that when controlling for age and sex, ethnic minorities were overall less likely than those born in Norway to be diagnosed with GD (odds ratio [OR] ranging from 0.293 to 0.698). After controlling for citizenship and years of residency in Norway, the results were reversed and indicated that ethnic minorities were overall more likely to be diagnosed with GD (OR ranging from 1.179 to 3.208).

Conclusion

The results suggest that citizenship and years of residency are important variables to account for when assessing the relationship between ethnicity and being diagnosed with GD. Our results may be explained by people from ethnic minority groups being more likely to experience gambling problems but less likely to seek contact with healthcare services for gambling problems.
Diminazene aceturate or losartan ameliorates the functional, radiological and histopathological alterations in knee osteoarthritis rodent model: repurposing of the ACE2/Ang1‐7/MasR cascade
Authors: Habib Yasser H. , Sheta Eman , Khattab Mahmoud , Gowayed Mennatallah A.
Published: October 2023

Purpose

Current therapies for osteoarthritis (OA) are limited to analgesics and anti‐inflammatory drugs. Considering the importance of oxidative stress and inflammatory mediators in OA etiology, we tested the hypothesis that targeting the renin–angiotensin–aldosterone system (RAAS) can improve OA anomalies. Diminazene (DIZE), an activator of angiotensin‐converting enzyme 2 and the angiotensin 2 type‐1 receptor blocker losartan (LOS) were used for this purpose.

Methods

OA was induced by a single intra‐articular injection of monosodium iodoacetate. The effects of exposure to DIZE or LOS for 21 days on OA anomalies in rats’ knees were investigated. Evaluation of motor function, nociception, and inflammatory response was done using rotarod, knee bend and knee swelling tests. Markers of knee joint inflammation, and cellular oxidation in addition to the RAAS biomarkers, were assessed in knee tissues, along with radiological and histopathological investigations.

Results

Elevations in inflammatory and oxidative markers in knee tissues of OA rats were mostly improved by the two therapeutic drugs. Such effect was also reflected in the rotarod, knee bend and knee swelling tests. Treatment with DIZE has shown a more prominent effect than LOS in controlling OA‐associated inflammation and cellular oxidation. Markers of RAAS have also shown better responsiveness to DIZE over LOS.

Conclusions

DIZE has shown a prominent increase in the angiotensin 1–7 amount, highlighting the involvement of the signaling pathway in the immunomodulatory effect. The radiological and histopathology examination came to confirm the outcome of biochemical markers, nominating diminazene aceturate as a possible therapeutic option for OA.
Photon-counting detector CT-based virtual monoenergetic reconstructions: repeatability and reproducibility of radiomics features of an organic phantom and human myocardium
Authors: Wolf Elias V. , Müller Lukas , Schoepf U. Joseph , Fink Nicola , Griffith Joseph P. , Zsarnoczay Emese , Baruah Dhiraj , Suranyi Pal , Kabakus Ismael M. , Halfmann Moritz C. , Emrich Tilman , Varga-Szemes Akos , O‘Doherty Jim
Published: October 2023

Background

Photon-counting detector computed tomography (PCD-CT) may influence imaging characteristics for various clinical conditions due to higher signal and contrast-to-noise ratio in virtual monoenergetic images (VMI). Radiomics analysis relies on quantification of image characteristics. We evaluated the impact of different VMI reconstructions on radiomic features in in vitro and in vivo PCD-CT datasets.

Methods

An organic phantom consisting of twelve samples (four oranges, four onions, and four apples) was scanned five times. Twenty-three patients who had undergone coronary computed tomography angiography on a first generation PCD-CT system with the same image acquisitions were analyzed. VMIs were reconstructed at 6 keV levels (40, 55, 70, 90, 120, and 190 keV). The phantoms and the patients’ left ventricular myocardium (LVM) were segmented for all reconstructions. Ninety-three original radiomic features were extracted. Repeatability and reproducibility were evaluated through intraclass correlations coefficient (ICC) and post hoc paired samples ANOVA t test.

Results

There was excellent repeatability for radiomic features in phantom scans (all ICC = 1.00). Among all VMIs, 36/93 radiomic features (38.7%) in apples, 28/93 (30.1%) in oranges, and 33/93 (35.5%) in onions were not significantly different. For LVM, the percentage of stable features was high between VMIs ≥ 90 keV (90 versus 120 keV, 77.4%; 90 versus 190 keV, 83.9%; 120 versus 190 keV, 89.3%), while comparison to lower VMI levels led to fewer reproducible features (40 versus 55 keV, 8.6%).

Conclusions

VMI levels influence the stability of radiomic features in an organic phantom and patients’ LVM; stability decreases considerably below 90 keV.

Relevance statement

Spectral reconstructions significantly influence radiomic features in vitro and in vivo, necessitating standardization and careful attention to these reconstruction parameters before clinical implementation.

Key points

• Radiomic features have an excellent repeatability within the same PCD-CT acquisition and reconstruction.

• Differences in VMI lead to decreased reproducibility for radiomic features.

• VMI ≥ 90 keV increased the reproducibility of the radiomic features.

Graphical Abstract
Adiabatic collapse of non-homogeneous self-gravitating gas cloud
Authors: Silveira F. E. M.
Published: October 2023

In this letter, we find the critical mass of a self-gravitating, spherically symmetric gas cloud, above which the fluid, within the bubble, collapses. Our analysis departs from a non-homogeneous equilibrium density, satisfying the Boltzmann relation. A time scale is defined in terms of the adiabatic index of the gas. Subsequently, a sinusoidal perturbation around equilibrium is regarded, thereby leading to a dispersion relation of frequency with wavelength, which does not depend on geometrical curvature effects. Such a formulation clearly justifies that the collapse occurs much faster than predicted by the well-known Jeans approach. The equilibrium profiles of the density, gravitational field, and potential are obtained as functions of the spherical radius coordinate at marginal instability. Since our theory captures the essential physics of gravitational collapse, it can be used as the starting point for several advancements in galactic dynamics.
Getting Past a Crisis Mentality
Authors: Tinkle Theresa
Published: October 2023

This opinion piece advocates for literature courses that examine the United States’ mental health crisis from the perspective of neurodiverse writers. This is not a short-term solution to the crisis, but over time courses can have a powerful impact on students’ attitudes toward and understanding of mental illness. Courses engaging in this work will advance the cause of social justice and the full inclusion of neurodiverse students and faculty in our classrooms and on our campuses.
Cultivating a Political Learning Ecology
Authors: Huseby Amy Kahrmann , Thierauf Doreen
Published: October 2023

This article details a collaboratively designed and taught honors course, Cultures of the Anthropocene: Climate Change and Survivance. The authors invite readers to consider interinstitutional political learning ecologies a viable and vibrant model of instruction for early-career scholars and experienced teachers seeking professional development and a profound pedagogical challenge.
Should You Kill the Spider?
Authors: Ioanes Anna
Published: October 2023

The appearance of a spider in the classroom can disrupt the flow of teaching, often prompting strong reactions that unsettle classroom norms. Minor classroom disruptions like this might not seem worth theorizing, but this essay reframes such disruptions as rich sites for understanding the role of affect in humanities pedagogy. Ultimately arguing against killing a spider in the classroom, this essay theorizes the moment of disruption as an opportunity to model humanistic attention to both human and nonhuman actors in the classroom space.
Surveillance and Pedagogy
Authors: Ball Tiffany Diana
Published: October 2023

This article examines the impact of video surveillance on teaching. Through a consideration of disciplinary power and paranoid reading debates, the author probes her personal experience at a university in Beijing, China. Surveillance inspires paranoia as well as an opportunity to reflect on the emotional life of academic inquiry in the classroom.
The influence of artificial intelligence on the work of the medical physicist in radiotherapy practice: a short review
Authors: Fiagbedzi Emmanuel , Hasford Francis , Tagoe Samuel Nii
Published: October 2023

There have been many applications and influences of Artificial intelligence (AI) in many sectors and its professionals, that of radiotherapy and the medical physicist is no different. AI and technological advances have necessitated changing roles of medical physicists due to the development of modernized technology with image-guided accessories for the radiotherapy treatment of cancer patients. Given the changing role of medical physicists in ensuring patient safety and optimal care, AI can reshape radiotherapy practice now and in some years to come. Medical physicists’ roles in radiotherapy practice have evolved to meet technology for the management of better patient care in the age of modern radiotherapy. This short review provides an insight into the influence of AI on the changing role of medical physicists in each specific chain of the workflow in radiotherapy in which they are involved.
Thyroid status in pregnancy: Comparison of thyroid function abnormalities in women with and without a history of miscarriage or stillbirth
Authors: Abbas Ghulam , Sabir Samina , Ur Rehman Siddiq , Gohar Beenish
Published: October 2023

Objective: To evaluate thyroid function tests (TFTs) during pregnancy in women with previous history of miscarriage or stillbirth.

Methods: A cross-sectional study was carried out at the department of Obstetrics & Gynaecology and Endocrinology, Lady Reading Hospital, Peshawar from February 2021 to March 2022. All multigravida women attending the antenatal clinics were included using consecutive sampling. These women were placed into two groups, Group-A comprised of women with no prior history of miscarriages or stillbirths, and those with a history of foetal death during previous pregnancies were assigned Group-B. Free T4, thyroid stimulating hormone (TSH) and anti-thyroid peroxidase (TPO) antibodies were measured and the former two were used to label patients with thyroid dysfunction.

Results: A total of 139 multigravida women were included in the study. About 43% of the women had a history of miscarriages or stillbirths. Thyroid dysfunction was observed overall in 36.69 % women, of whom 25.18% had sub-clinical hypothyroidism, 6.47% had hypothyroidism and 5.04 % were sub-clinical hyperthyroid. Women in Group-B had more thyroid functions abnormalities compared to Group-A (p<0.05). Moreover, there was significant difference in median TSH and freeT4 between the groups (p<0.001). Overall, thyroid dysfunction was found in 66.67% of patients who had a history of foetal death.

Conclusions: In pregnant women with a history of miscarriage or abortion, thyroid functions abnormalities are common therefore routine thyroid testing is advised in pregnant women to prevent adverse perinatal outcomes.

doi: https://doi.org/10.12669/pjms.40.1.7282

How to cite this: Abbas G, Sabir SA, Siddiq Ur Rehman, Gohar B. Thyroid status in pregnancy: Comparison of thyroid function abnormalities in women with and without a history of miscarriage or stillbirth. Pak J Med Sci. 2024;40(1):---------.  doi: https://doi.org/10.12669/pjms.40.1.7282

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Correlation between the risk of lymph node metastasis and the expression of GBP1 in breast cancer patients
Authors: Liu Yukun , Wu Ziying , Lin Jun , Wang Zhimei
Published: October 2023

Objective: To explore the prognostic value and correlation between the risk of lymph node metastasis (LNM) and Guanylate-binding Protein 1 (GBP1) in breast cancer (BC) patients.

Methods: In this retrospective study, the clinical data of 150 patients with BC who were surgically resected in The Affiliated Qingdao Central Hospital of Qingdao University from January 2019 to December 2021 were included. Patients were divided into metastasis group (n=110) or non-metastasis group (n=40) according to whether there was LNM post-surgery. Logistic regression was used to analyze the risk factors for LNM in BC, and Kaplan-Meier was used to assess the risk of disease progression 12 months post-operation in both groups. Patients were divided into a GBP1 low expression-group (n=75) or a GBP1 high expression-group (n=75). The risk of disease progression, one-year post-surgery was analyzed, and the predictive value of GBP1 in BC tissue was assessed by the receiver operating characteristics (ROC) curve.

Results: Independent risk factors for BC with LNM were GBP1, CEA and TNM stage (P<0.05). There is a linear relationship between GBP1 expression and LNM risk in BC (χ2=0.88, P<0.05). Patients with high expression of GBP1 had a higher risk of LNM (χ2=3.204, P<0.001) and early postoperative progression (χ2=7.412, P<0.05). The AUC of GBP1 in predicting the risk of LNM was 0.840.

Conclusions: Patients with BC and a higher expression of GBP1 could be at an increased risk of LNM. Elevations in GBP1 expression can also suggest a poor prognosis for patients with BC.

doi: https://doi.org/10.12669/pjms.40.1.8251

How to cite this: Liu Y, Wu Z, Lin J, Wang Z. Correlation between the risk of lymph node metastasis and the expression of GBP1 in breast cancer patients. Pak J Med Sci. 2024;40(1):---------. doi: https://doi.org/10.12669/pjms.40.1.8251

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.