bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Phosphorylation and Redox Status: An as Yet Elusive Dyad in Chronic Lymphocytic Leukemia
Authors: Pagano Mario Angelo , Frezzato Federica , Visentin Andrea , Trentin Livio , Brunati Anna Maria
Published: October 2022

Malignant cells in chronic lymphocytic leukemia (CLL) are characterized by oxidative stress that is related to abundant generation of reactive oxygen species (ROS) by increased mitochondrial oxidative phosphorylation (OXPHOS). Lymphoid tissues have been shown to provide a protective microenvironment that antagonizes the effects of ROS, contributing to establishing redox homeostasis that supports the vitality of CLL cells. In the last few decades, a complex antioxidant machinery has been demonstrated to be activated in CLL cells, including the different superoxide dismutase (SOD) isoforms, the thioredoxin (Trx) system, and the enzyme cascade inducing glutathione (GSH) biosynthesis and recycling, to name a few. Their expression is known to be upregulated by the activation of specific transcription factors, which can be regulated by either oxidative stress or phosphorylation. These two latter aspects have mostly been explored separately, and only recently an increasing body of evidence has been providing reasonable inference that ROS and phosphorylation may cooperate in an interplay that contributes to the survival mechanisms of CLL cells. Here, we present an overview of how oxidative stress and phosphorylation-dependent signals are intertwined in CLL, focusing on transcription factors that regulate the balance between ROS production and scavenging.
Circulating Cell-Free DNA-Based Methylation Pattern in Saliva for Early Diagnosis of Head and Neck Cancer
Authors: Birknerova Natalia , Mancikova Veronika , Paul Evan David , Matyasovsky Jan , Cekan Pavol , Palicka Vladimir , Parova Helena
Published: October 2022

Head and neck cancer (HNC) remains one of the leading causes of mortality worldwide due to tumor diagnosis at a late stage, loco-regional aggression, and distant metastases. A standardized diagnostic procedure for HNC is a tissue biopsy that cannot faithfully portray the in-depth tumor dynamics. Therefore, there is an urgent need to develop simple, accurate, and non-invasive methods for cancer detection and follow-up. A saliva-based liquid biopsy allows convenient, non-invasive, and painless collection of high volumes of this biofluid, with the possibility of repetitive sampling, all enabling real-time monitoring of the disease. No approved clinical test for HNC has yet been established. However, epigenetic changes in saliva circulating cell-free DNA (cfDNA) have the potential for a wide range of clinical applications. Therefore, the aim of this review is to present an overview of cfDNA-based methylation patterns in saliva for early detection of HNC, with particular attention to circulating tumor DNA (ctDNA). Due to advancements in isolation and detection technologies, as well as next- and third-generation sequencing, recent data suggest that salivary biomarkers may be successfully applied for early detection of HNC in the future, but large prospective clinical trials are still warranted.
Utilizing an Endogenous Progesterone Receptor Reporter Gene for Drug Screening and Mechanistic Study in Endometrial Cancer
Authors: Li Yiyang , Zhou Wei , Meng Xiangbing , Murray Sarina D. , Li Long , Fronk Abby , Lazaro-Camp Vanessa J. , Wen Kuo-kuang , Wu Meng , Dupuy Adam , Leslie Kimberly K. , Yang Shujie
Published: October 2022

Expression of progesterone receptor (PR) is a favorable prognostic marker for multiple solid tumors. However, PR expression is reduced or lost in malignant tumors. Thus, monitoring and restoring functional PR expression is important in order to sensitize tumor cells to progesterone therapy in endometrial cancer. We developed stable PR reporter gene containing endometrial cancer cell lines monitoring the endogenous PR expression by inserting mCherry and hygromycin resistant gene at the endogenous PR gene locus by CRISPR/Cas9-mediated genome editing technique. This allows efficient, real-time monitoring of PR expression in its native epigenetic landscape. Reporter gene expression faithfully reflects and amplifies PR expression following treatment with drugs known to induce PR expression. Small molecular PR inducers have been identified from the FDA-approved 1018 drug library and tested for their ability to restore PR expression. Additionally, several candidate PR repressors have been identified by screening the genome-wide CRISPR knockout (GeCKO) library. This novel endogenous PR reporter gene system facilitates the discovery of a new treatment strategy to enhance PR expression and further sensitize progestin therapy in endometrial cancer. These tools provide a systematic, unbiased approach for monitoring target gene expression, allowing for novel drug discovery and mechanistic exploration.
Tumor Microenvironment, Clinical Features, and Advances in Therapy for Bone Metastasis in Gastric Cancer
Authors: Sun Pengcheng , Antwi Samuel O. , Sartorius Kurt , Zheng Xiao , Li Xiaodong
Published: October 2022

Gastric cancer (GC) is one of the most malignant neoplasms worldwide, accounting for about 770,000 deaths in 2020. The incidence of gastric cancer bone metastasis (GC-BM) is low, about 0.9–13.4%, and GC patients develop GC-BM because of a suitable bone microenvironment. Osteoblasts, osteoclasts, and tumor cells interact with each other, secreting cytokines such as PTHrP, RANK-L, IL-6, and other growth factors that disrupt the normal bone balance and promote tumor growth. The functions and numbers of immune cells in the bone microenvironment are continuously inhibited, resulting in bone balance disorder due to the cytokines released from destroyed bone and growing tumor cells. Patients with GC-BM are generally younger than 65 years old and they often present with a later stage of the disease, as well as more aggressive tumors. They usually have shorter overall survival (OS) because of the occurrence of skeletal-related events (SREs) and undetected bone destruction due to the untimely bone inspection. Current treatments of GC-BM focus mainly on gastric cancer and SRE-related treatment. This article reviews the clinical features, possible molecular pathogeneses, and the most commonly used diagnostic methods and treatments of bone metastasis in gastric cancer.
HPV16 E7 Nucleotide Variants Found in Cancer-Free Subjects Affect E7 Protein Expression and Transformation
Authors: Lou Hong , Boland Joseph F. , Li Hongchuan , Burk Robert , Yeager Meredith , Anderson Stephen K. , Wentzensen Nicolas , Schiffman Mark , Mirabello Lisa , Dean Michael
Published: October 2022

The human papillomavirus (HPV) type 16 E7 oncogene is critical to carcinogenesis and highly conserved. Previous studies identified a preponderance of non-synonymous E7 variants amongst HPV16-positive cancer-free controls compared to those with cervical cancer. To investigate the function of E7 variants, we constructed full-length HPV16 E7 genes and tested variants at positions H9R, D21N, N29S, E33K, T56I, D62N, S63F, S63P, T64M, E80K, D81N, P92L, and P92S (found only in controls); D14E, N29H cervical intraepithelial neoplasia (CIN2), and P6L, H51N, R77S (CIN3). We determined the steady-state level of cytoplasmic and nuclear HPV16 E7 protein. All variants from controls showed a reduced level of E7 protein, with 7/13 variants having lower protein levels. In contrast, 2/3 variants from the CIN3 precancer group had near-wild type E7 levels. We assayed the activity of representative variants in stably transfected NIH3T3 cells. The H9R, E33K, P92L, and P92S variants found in control subjects had lower transforming activity than D14E and N29H variants (CIN2), and the R77S (CIN3) had activity only slightly reduced from wild-type E7. In addition, R77S and WT E7 caused increased migration of NIH3T3 cells in a wound-healing assay compared with H9R, E33K, P92L, and P92S (controls) and D14E (CIN2). These data provide evidence that the E7 variants found in HPV16-positive cancer-free women are partially defective for transformation and cell migration, further demonstrating the importance of fully active E7 in cancer development.
Primary Resistance to Immunotherapy-Based Regimens in First Line Hepatocellular Carcinoma: Perspectives on Jumping the Hurdle
Authors: Salani Francesca , Genovesi Virginia , Vivaldi Caterina , Massa Valentina , Cesario Silvia , Bernardini Laura , Caccese Miriam , Graziani Jessica , Berra Dario , Fornaro Lorenzo , Masi Gianluca
Published: October 2022

Immune checkpoint inhibitors (ICIs) are a key component of different stages of hepatocellular carcinoma (HCC) treatment, particularly in the first line of treatment. A lesson on the primary resistance which hampers their efficacy and activity was learned from the failure of the trials which tested them as first-line mono-therapies. Despite the combination of anti-PD(L)1 agents with anti-VEGF, anti CTLA4, or TKIs demonstrating relevant improvements in efficacy, the “doublets strategy” still shows room for improvement, due to a limited overall survival benefit and a high rate of progressive disease as best response. In this review, we discuss the results from the currently tested doublet strategies (i.e., atezolizumab+bevacizumab, durvalumab+tremelimumab with a mention to the newly presented ICIs/TKIs combinations), which highlight the need for therapeutic improvement. Furthermore, we examine the rationale and provide an overview of the ongoing trials testing the treatment intensification strategy with triplet drugs: anti-PD1+anti-CTLA4+anti-VEGF/TKIs and anti-PD1+anti-VEGF+alternative immunity targets. Lastly, we report on the alternative strategy to integrate ICIs into the new paradigm of immune therapeutics constituted by CAR-T and anti-cancer vaccines. This review provides up-to-date knowledge of ongoing clinical trials of the aforementioned strategies and critical insight into their mechanistic premises.
Targeting Triple Negative Breast Cancer Stem Cells by Heat Shock Protein 70 Inhibitors
Authors: Tsai Chia-Hung , Weng Jing-Ru , Lin Hsiang-Wen , Lu Meng-Tien , Liu Yu-Chi , Chu Po-Chen
Published: October 2022

Triple negative breast cancer (TNBC) is considered the most aggressive breast cancer with high relapse rates and poor prognosis. Although great advances in the development of cancer therapy have been witnessed over the past decade, the treatment options for TNBC remain limited. In this study, we investigated the effect and potential underlying mechanism of the Hsp70 inhibitors, compound 1 and compound 6, on breast cancer stem cells (BCSCs) in TNBC cells. Our results showed that compound 1 and 6 exhibited potent tumor suppressive effects on cell viability and proliferation, and effectively inhibited BCSC expansion in TNBC cells. Reminiscent with the effect of Hsp70 inhibitors, Hsp70 knockdown effectively suppressed mammosphere formation and the expressions of BCSCs surface markers. Mechanistically, evidence showed that the Hsp70 inhibitors inhibited BCSCs by down-regulating β-catenin in TNBC cells. Moreover, we used the Hsp70 inhibitors treated TNBC cells and a stable Hsp70 knockdown clone of MDA-MB-231 cells to demonstrate the in vivo efficacy of Hsp70 inhibition in suppressing tumorigenesis and xenograft tumor growth. Together, these findings suggest the potential role of Hsp70 as a target for TNBC therapy and foster new therapeutic strategies to eliminate BCSCs by targeting Hsp70.
Differential Expression of HIF1A, EPAS1, and VEGF Genes in Benign and Malignant Ovarian Neoplasia
Authors: Englert-Golon Monika , Tokłowicz Małgorzata , Żbikowska Aleksandra , Sajdak Stefan , Kotwicka Małgorzata , Andrusiewicz Mirosław
Published: October 2022

Ovarian cancer (OC) has the highest mortality rate of all gynecological malignancies. Moreover, at the time of the first clinical manifestation, most patients have an advanced stage of the disease. Our study examined differences in mRNA levels of hypoxia-inducible factor 1-alpha (HIF1A); endothelial PAS domain protein 1, also known as hypoxia-inducible factor 2-alpha (HIF2A/EPAS1); and vascular endothelial growth factor A (VEGFA) between cancerous tissue, benign hyperplastic changes in the ovary, and normal tissue. Our cohorts consisted of 52 patients diagnosed with OC (n = 55), benign non-cancerous changes (n = 21), and normal tissue samples (n = 38). The mRNA expression level was evaluated using RT-qPCR. We found that gene expression changes were visible not only in the case-control study, but also along with changes in severity. Additionally, the gene expression was differentiated in age, BMI, menopausal status, and the number of comorbidy-related groups. Furthermore, our findings demonstrate that analyzing the correlation between genes is essential. In a case-to-case and case-to-control study, we observed disturbances in the expression levels of interdependent genes. Our findings suggest that mutual association in the expression of both HIF1A and HIF2A/EPAS1 with VEGFA has prognostic importance for patients with OC. Our observations may help identify patients for clinical trials aimed at inhibiting the hypoxia-induced neovascularization-dependent pathways.
Invasion-Associated Reorganization of Laminin 332 in Oral Squamous Cell Carcinomas: The Role of the Laminin γ2 Chain in Tumor Biology, Diagnosis, and Therapy
Authors: Berndt Alexander , Gaßler Nikolaus , Franz Marcus
Published: October 2022

Invasion of the connective tissue by carcinoma cells is accompanied by disintegration and reorganization of the hemidesmosomes, which connect the basement membrane to the basal epithelial cells. In terms of mediating the basement membrane, i.e., basal cell interactions, the heterotrimeric laminin 332 is the most important bridging molecule. Due to this distinct function, laminin 332, especially its gamma 2 chain, came into the focus of cancer research. Specific de novo synthesis and deposition patterns of laminin 332 are evident upon development and progression of oral squamous cell carcinomas (OSCCs). Loss from the basement membrane, cytoplasmic accumulation, and extracellular deposition are associated with crucial processes such as stromal activation and immune response, epithelial to mesenchymal transition, and tumor cell budding. In networks with components of the tumor microenvironment, altered expression of laminin 332 chains, proteolytic processing, and interaction with integrin receptors seem to promote cancer cell migration. Indeed, reorganization patterns are shown to have a high diagnostic and prognostic value. Here, we summarize the current knowledge on laminin 332 reorganization in OSCCs with special focus on its gamma 2 chain and provide, based on the current literature, evidence on its promising role as a grading and monitoring parameter and as a potential therapeutic target.
Construction of Brain Metastasis Prediction Model and Optimization of Prophylactic Cranial Irradiation Selection for Limited-Stage Small-Cell Lung Cancer
Authors: Hou Qing , Sun Bochen , Yao Ningning , Liang Yu , Cao Xin , Wei Lijuan , Cao Jianzhong
Published: October 2022

Prophylactic cranial irradiation (PCI), as an essential part of the treatment of limited-stage small-cell lung cancer (LS-SCLC), inevitably leads to neurotoxicity. This study aimed to construct a brain metastasis prediction model and identify low-risk patients to avoid PCI; 236 patients with LS-SCLC were retrospectively analyzed and divided into PCI (63 cases) and non-PCI groups (173 cases). The nomogram was developed based on variables determined by univariate and multivariate analyses in the non-PCI group. According to the cutoff nomogram score, all patients were divided into high- and low-risk cohorts. A log-rank test was used to compare the incidence of brain metastasis between patients with and without PCI in the low-risk and high-risk groups, respectively. The nomogram included five variables: chemotherapy cycles (ChT cycles), time to radiotherapy (RT), lactate dehydrogenase (LDH), pro-gastrin-releasing peptide precursor (ProGRP), and lymphocytes–monocytes ratio (LMR). The area under the receiver operating characteristics (AUC) of the nomogram was 0.763 and 0.782 at 1 year, and 0.759 and 0.732 at 2 years in the training and validation cohorts, respectively. Based on the nomogram, patients were divided into high- and low-risk groups with a cutoff value of 165. In the high-risk cohort, the incidence of brain metastasis in the non-PCI group was significantly higher than in the PCI group (p < 0.001), but there was no difference in the low-risk cohort (p = 0.160). Propensity score-matching (PSM) analysis showed similar results; the proposed nomogram showed reliable performance in assessing the individualized brain metastasis risk and has the potential to become a clinical tool to individualize PCI treatment for LS-SCLC.
Prostate-Specific Antigen Bounce after 125I Brachytherapy Using Stranded Seeds with Intraoperative Optimization for Prostate Cancer
Authors: Kim Tae Hyung , Lee Jason Joon Bock , Cho Jaeho
Published: October 2022

Prostate-specific antigen (PSA) bounce is common in patients undergoing 125I brachytherapy (BT), and our study investigated its clinical features. A total of 100 patients who underwent BT were analyzed. PSA bounce and large bounce were defined as an increase of ≥0.2 and ≥2.0 ng/mL above the initial PSA nadir, respectively, with a subsequent decline without treatment. Biochemical failure was defined using the Phoenix definition (nadir +2 ng/mL), except for a large bounce. With a median follow-up of 49 months, 45% and 7% of the patients experienced bounce and large bounce, respectively. The median time to bounce was 24 months, and the median PSA value at the bounce spike was 1.62 ng/mL, a median raise of 0.44 ng/mL compared to the pre-bounce nadir. The median time to bounce recovery was 4 months. The post-bounce nadir was obtained at a median of 36 months after low-dose-rate BT. On univariate analysis, age, the PSA nadir value at 2 years, and prostate volume were significant factors for PSA bounce. The PSA nadir value at 2 years remained significant in multivariate analysis. We should carefully monitor young patients with high prostate volume having a >0.5 PSA nadir value at 2 years for PSA bounce.
Does Lactobacillus Exert a Protective Effect on the Development of Cervical and Endometrial Cancer in Women?
Authors: Frąszczak Karolina , Barczyński Bartłomiej , Kondracka Adrianna
Published: October 2022

Cervical cancer is a significant health problem with increasing occurrence and mortality. This infection-associated tumour is caused by the human papillomavirus (HPV). HPV infection is cleared by the immune system within 6–18 months in most patients; however, persistent high-risk HPV (hrHPV) infections can lead to the development of cervical cancer. Virus persistence is promoted by immunodeficiency, Chlamydia trachomatis infection, smoking, and age, as well as the imbalance of cervicovaginal microbiota and inflammation. The abundance of bacteria in the vagina favours the maintenance of a dynamic balance; their coexistence influences health or disease states. The eubiotic vaginal microbiota of reproductive-aged women is composed mostly of various Lactobacillus species (spp.), which exert protective effects via the production of lactic acid, bacteriocins, polysaccharides, peptidoglycans, and hydrogen peroxide (H2O2), lowering pH, raising the viscosity of cervicovaginal mucus, and hampering both the adhesion of cells to epithelial tissue and the entry of HPV. The depletion of beneficial microorganisms could increase the risk of sexually transmitted infections. Emerging therapies involve mucosal, intranasal vaccines, which trigger systemic and mucosal immune responses, thus protecting against HPV-induced tumours. The use of probiotics has also been suggested to affect various biological processes associated with tumourigenesis (inflammation, oxidative stress, apoptosis, proliferation, and metastasis).
The GBM Tumor Microenvironment as a Modulator of Therapy Response: ADAM8 Causes Tumor Infiltration of Tams through HB-EGF/EGFR-Mediated CCL2 Expression and Overcomes TMZ Chemosensitization in Glioblastoma
Authors: Liu Xiaojin , Huang Yimin , Qi Yiwei , Wu Shiqiang , Hu Feng , Wang Junwen , Shu Kai , Zhang Huaqiu , Bartsch Jörg W. , Nimsky Christopher , Dong Fangyong , Lei Ting
Published: October 2022

Standard chemotherapy of Glioblastoma multiforme (GBM) using temozolomide (TMZ) frequently fails due to acquired chemoresistance. Tumor-associated macrophages and microglia (TAMs) as major immune cell population in the tumor microenvironment are potential modulators of TMZ response. However; little is known about how TAMs participate in TMZ induced chemoresistance. Members of the metzincin superfamily such as Matrix Metalloproteases (MMPs) and A Disintegrin and Metalloprotease (ADAM) proteases are important mediators of cellular communication in the tumor microenvironment. A qPCR screening was performed to identify potential targets within the ADAM and MMP family members in GBM cells. In co-culture with macrophages ADAM8 was the only signature gene up-regulated in GBM cells induced by macrophages under TMZ treatment. The relationship between ADAM8 expression and TAM infiltration in GBM was determined in a patient cohort by qPCR; IF; and IHC staining and TCGA data analysis. Moreover; RNA-seq was carried out to identify the potential targets regulated by ADAM8. CCL2 expression levels were determined by qPCR; Western blot; IF; and ELISA. Utilizing qPCR; IF; and IHC staining; we observed a positive relationship between ADAM8 expression and TAMs infiltration level in GBM patient tissues. Furthermore; ADAM8 induced TAMs recruitment in vitro and in vivo. Mechanistically; we revealed that ADAM8 activated HB-EGF/EGFR signaling and subsequently up-regulated production of CCL2 in GBM cells in the presence of TMZ treatment; promoting TAMs recruitment; which further induced ADAM8 expression in GBM cells to mediate TMZ chemoresistance. Thus; we revealed an ADAM8 dependent positive feedback loop between TAMs and GBM cells under TMZ treatment which involves CCL2 and EGFR signaling to cause TMZ resistance in GBM.
Age Specific Risks of Uterine Cancer in Type 2 Diabetes and Associated Comorbidities in Taiwan
Authors: Liu Hui-Shan , Chen Chin-Der , Lee Chung-Chen , Chen Yong-Chen , Cheng Wen-Fang
Published: October 2022

Introduction: The global incidence of uterine cancer has increased substantially in recent decades. We evaluated if the trend of increasing prevalence of diabetes mellitus (DM) and obesity are attributed to the development of uterine cancer. Methods: Using data derived from the National Health Insurance database and Taiwan Cancer Registry, multivariate Cox proportional hazards regression models were adapted to analyze the risk factors of uterine cancer with potential confounding variables. Results: There were a total of 5,104,242 women aged 30–70 years enrolled in the study and 147,772 of them were diagnosed with DM during 2005–2007. In a total of 11 years of follow-up, 14,398 subjects were diagnosed with uterine cancer. An elevated risk of uterine cancer was observed in women with DM of all ages (HR 1.66, 95% CI 1.53–1.81, p < 0.0001). The effect of DM was highest at age 30–39 years (RR 3.05, 95% CI 2.35–3.96, p < 0.0001). In the group of <50 years old, DM patients had at least a twofold higher risk of developing uterine cancer (HR 2.39, 95% CI 2.09–2.74, p < 0.0001). Subjects among all ages diagnosed with polycystic ovary syndrome (PCOS) (HR 2.91, 95% CI 2.47–3.42, p < 0.0001), obesity (HR 2.13, 95% CI 1.88–2.41, p < 0.0001), and those undergoing hormone replacement therapy (HRT) (HR 1.60, 95% CI 1.33–1.93, p < 0.0001) were also positively associated with uterine cancer. Positive associations of hyperlipidemia (HR 1.33, 95% CI 1.22–1.46, p < 0.0001) and statin use (HR 1.27, 95% CI 1.12–1.44, p = 0.0002) on uterine cancer were only observed in subjects <50 years. On the contrary, hyperlipidemia was negatively associated with uterine cancer in subjects ≥50 years (HR 0.91, 95% CI: 0.84–0.98, p = 0.0122). Conclusions: DM is in general the most important risk factor for uterine cancer, especially in premenopausal women. Obesity, PCOS, HPL, statin use, and HRT were also associated with uterine cancer in subjects younger than 50 years. Premenopausal women with DM and respective comorbidities should be aware of the development of uterine cancer.
Second Primary Malignancy Risk in Multiple Myeloma from 1975 to 2018
Authors: Wang Jing , Lv Chenglan , Zhou Min , Xu Jing-Yan , Chen Bing , Wan Yuan
Published: October 2022

As the survival times for multiple myeloma (MM) patients continue to extend, the risk of a second primary malignancy (SPM) among MM survivors has become a topic of increasing concern within the medical community. The Surveillance, Epidemiology, and End Results (SEER) 9 Registry Database was used to evaluate the risk and survival of SPM among MM survivors from 1975 to 2018. The standardized incidence ratio (SIR), absolute excess risk (AER), and cumulative incidence (CMI) of SPM for MM risk were calculated. Survival and the CMI were estimated by using hazard ratios (HRs). Subgroup analyses were performed according to race, sex, age, time of myeloma diagnosis, and the SPM site. A total of 43,825 cases were recorded with the initial diagnosis of MM from 1975 to 2018. A total of 3101 (7.1%) patients developed 3407 SPMs. Solid tumors were decreased in patients with MM (SIR = 0.93; 95% CI = 0.90–0.97) compared to the general population, whereas the risk of hematological malignancy was increased (SIR = 1.90; 95% CI = 1.72–2.10). Taking death as a competing event, the CMI of SPM in the whole population was 7.38% at 10 years (6.11% solid and 1.27% hematologic). Factors associated with SPM occurrence were age, sex, race, and time of MM diagnosis. The survival of SPM patients from MM diagnosis was longer than that of patients without SPM (HR = 0.67, 95% CI = 0.58–0.63). The median survival time was 17 months from SPM diagnosis and 34 months from MM diagnosis (HR = 1.4, 95% CI = 1.35–1.46). Age, race, and sex were important factors for the risk of SPM. Site- and time-specific surveillance strategies should be recommended to monitor SPM in high-risk MM patients.
Enzymatic Formation of Protectin Dx and Its Production by Whole-Cell Reaction Using Recombinant Lipoxygenases
Authors: Shin Kyung-Chul , Lee Tae-Eui , Kim Su-Eun , Ko Yoon-Joo , Seo Min-Ju , Oh Deok-Kun
Published: October 2022

In the human body, docosahexaenoic acid (DHA) contained in fish oil is converted to trace amounts of specialized pro-resolving mediators (SPMs) as the principal bioactive metabolites for their pharmacological effects. Protectin Dx (PDX), an SPM, is an important medicinal compound with biological activities such as modulation of endogenous antioxidant systems, inflammation pro-resolving action, and inhibition of influenza virus replication. Although it can be biotechnologically synthesized from DHA, it has not yet been produced quantitatively. Here, we found that 15S-lipoxygenase from Burkholderia thailandensis (BT 15SLOX) converted 10S-hydroxydocosahexaenoic acid (10S-HDHA) to PDX using enzymatic reactions, which was confirmed by LC-MS/MS and NMR analyses. Thus, whole-cell reactions of Escherichia coli cells expressing BT 15SLOX were performed in flasks to produce PDX from lipase-treated DHA-enriched fish oil along with E. coli cells expressing Mus musculus (mouse) 8S-lipoxygenase (MO 8SLOX) that converted DHA to 10S-HDHA. First, 1 mM DHA (DHA-enriched fish oil hydrolysate, DFOH) was obtained from 455 mg/L DHA-enriched fish oil by lipase for 1 h. Second, E. coli cells expressing MO 8SLOX converted 1 mM DHA in DFOH to 0.43 mM 10S-HDHA for 6 h. Finally, E. coli cells expressing BT 15SLOX converted 0.43 mM 10S-HDHA in MO 8SLOX-treated DFOH to 0.30 mM (108 mg/L) PDX for 5 h. Consequently, DHA-enriched fish oil at 455 mg/L was converted to 108 mg/L PDX after a total of 12 h (conversion yield: 24% (w/w); productivity: 4.5 mg/L/h). This study is the first report on the quantitative production of PDX via biotechnological approaches.
Organocatalytic Synthesis of α-Aminonitriles: A Review
Authors: Ullah Bakhtar , Gupta Navneet Kumar , Ke Quanli , Ullah Naseeb , Cai Xingke , Liu Dongqing
Published: October 2022

α-Aminonitriles, which have anticancer, antibacterial, antiviral, and antifungal properties, have played an important role in pharmacology. Furthermore, they can also be used to synthesize natural and unnatural amino acids. The main bottleneck in the commercialization of these products is their large-scale production with controlled chirality. A variety of methods have been used to synthesize α-aminonitriles. Among other reported methods for preparing α-aminonitriles, the Strecker reaction is considered appropriate. Recent developments, however, have enabled the α-cyanation of tertiary and secondary amines by functionalizing the carbon–hydrogen (C–H) bond as an attractive alternative procedure for the preparation of α-aminonitriles in the presence of an oxidant and a cyanide source. In most cases, these reactions are catalyzed by transition metal catalysts, such as Fe, Cu, Rh, V, Au, Ru, Mo, Pt, Re, and Co, or by photocatalysts. As an alternative, organocatalysts can also be used to produce aminonitriles. Although there have been numerous reviews on the preparation of α-aminonitriles, no such reviews have been published specifically on the organocatalyzed synthesis of α-aminonitriles. Organocatalysis plays a significant role in synthesizing α-aminonitriles via Strecker-type reactions and cross dehydrogenative coupling reactions (CDC). In this mini review, we discuss the organocatalyzed synthesis of these molecules. A review of new organocatalysts for the synthesis of aminonitriles is expected to provide insight into the development of new industrial catalysts.
Agri-Biodegradable Mulch Films Derived from Lignin in Empty Fruit Bunches
Authors: Sirivechphongkul Kittitat , Chiarasumran Nutchapon , Saisriyoot Maythee , Thanapimmetha Anusith , Srinophakun Penjit , Iamsaard Kesinee , Lin Yao-Tung
Published: October 2022

Mulch films increase soil temperature, maintain soil moisture, improve water and fertilizer absorption, and reduce weed growth. This work studied a mulching film made using polyvinyl alcohol (PVA) and lignin extracted from empty fruit bunches (EFBs). The mulch films were investigated for opaqueness, biodegradation, water-solubility, absorption, and mechanical properties. Life cycle assessment (LCA) and cost estimate analysis were conducted. The composite mulch film-PVA solution was blended with 6% EFB lignin in dimethyl sulfoxide (DMSO) solution using five different amounts (0, 20, 40, 60, or 80 wt% lignin). The results showed that increasing the amount of lignin increased the film’s water solubility, moisture content, and biodegradability. At the same time, water absorption tended to decrease. Consequently, the light transmittance of the film was reduced, which had a positive effect on preventing soil weed growth. Tests of the mechanical properties showed that 60% lignin in the PVA film had the highest tensile strength (16.293 MPa). According to the LCA studies and cost estimation, the lignin-mixed PVA film had the lowest impact and was cheaper than the commercial mulching film. The results suggested that it is possible to blend polyvinyl alcohol polymer with lignin to improve biodegradability up to 25.47% by soil burial and 32% by water solubility.
Tailoring Structure: Current Design Strategies and Emerging Trends to Hierarchical Catalysts
Authors: Venezia Virginia , Pota Giulio , Silvestri Brigida , Costantini Aniello , Vitiello Giuseppe , Luciani Giuseppina
Published: October 2022

Nature mimicking implies the design of nanostructured materials, which can be assembled into a hierarchical structure, thus outperforming the features of the neat components because of their multiple length scale organization. This approach can be effectively exploited for the design of advanced photocatalysts with superior catalytic activity for energy and environment applications with considerable development in the recent six years. In this context, we propose a review on the state of the art for hierarchical photocatalyst production. Particularly, different synthesis strategies are presented, including template-free structuring, and organic, inorganic, and hybrid templating. Furthermore, emerging approaches based on hybrid and bio-waste templating are also highlighted. Finally, a critical comparison among available methods is carried out based on the envisaged application.
The Synthesis of Cu–Mn–Al Mixed-Oxide Combustion Catalysts by Co-Precipitation in the Presence of Starch: A Comparison of NaOH with Organic Precipitants
Authors: Napruszewska Bogna D. , Walczyk Anna , Duraczyńska Dorota , Kryściak-Czerwenka Joanna , Michalik Alicja , Karcz Robert , Śliwa Michał , Serwicka Ewa M.
Published: October 2022

Cu–Mn mixed oxides are well known as active combustion catalysts. The common method for their synthesis is based on co-precipitation, with NaOH as a precipitant, and is burdened with the possibility of introducing undesired Na contamination. This work describes the use of two organic bases, tetrabutylammonium hydroxide and choline hydroxide, as precipitating agents in a novel alkali-free route for Cu–Mn–Al catalyst synthesis. To obtain fine crystalline precursors, which are considered advantageous for the preparation of active catalysts, co-precipitation was carried out in the presence of starch gel. Reference materials prepared with NaOH in the absence of starch were also obtained. Mixed oxides were produced by calcination at 450 °C. The precursors contained MnCO3 doped with Cu and Al, and an admixture of amorphous phases. Those prepared in the presence of starch were less crystalline and retained biopolymer residues. The combustion of these residues during calcination enhanced the formation of larger amounts of the Cu1.5Mn1.5O4 spinel phase, with better crystallinity in comparison to catalysts prepared from conventionally synthesized precursors. Tests of toluene combustion demonstrated that the catalysts prepared with starch performed better than those obtained in starch-free syntheses, and that the mixed oxides obtained by the alkali-free route were more active than catalysts prepared with NaOH. Catalytic data are discussed in terms of property–performance relationships.
Zinc Oxide–Graphene Nanocomposite-Based Sensor for the Electrochemical Determination of Cetirizine
Authors: Sawkar Rakesh R. , Shanbhag Mahesh M. , Tuwar Suresh M. , Mondal Kunal , Shetti Nagaraj P.
Published: October 2022

A nanocomposite electrode of graphene (Gr) and zinc oxide (ZnO) nanoparticles was fabricated to study the electrochemical oxidation behavior of an anti-inflammatory drug, i.e., cetirizine (CET). The voltametric response of CET for bare CPE, Gr/CPE, ZnO/CPE, and the ZnO-Gr nanocomposite electrode was studied. The modifier materials were characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray powder diffraction (XRD) to comprehend the surface morphology of the utilized modifiers. The influence of pH, scan rate, and accumulation time on the electrooxidation of CET was examined. It was found that the electrochemical oxidation of CET was diffusion-controlled, in which two protons and two electrons participated. The detection limit was found to be 2.8 × 10−8 M in a linearity range of 0.05–4.0 µM. Study of excipients was also performed, and it was found that they had negligible interference with the peak potential of CET. The validation and utility of the fabricated nanocomposite sensor material were examined by analyzing clinical and biological samples. Stability testing of the nanocomposite electrode was conducted to assess the reproducibility, determining that the developed biosensor has good stability and high efficiency in producing reproducible results.
Insight into the Effects of Inorganic Element Catalysis and Basic Fuel Properties on the Self-Sustained Smoldering Process of Sewage Sludge
Authors: Zhang Wei , Wang Xiaowei , Song Qianshi , Chen Qianyi , Li Haowen , Yang Zixin , Wang Xiaohan
Published: October 2022

The objective of this study is to investigate the effects of inorganic element catalysis and basic fuel properties of sewage sludge on pyrolysis kinetics and self-sustained smoldering characteristics. The sludge pyrolysis process was explored by thermogravimetric and iso-conversion methods, and it was found that the pyrolysis process can be divided into two stages, which are mainly determined by the organic and inorganic components of the fuel. The inorganic components (e.g., Na, Fe and Mn) have a significant catalytic effect on the release of volatiles and the decomposition of macromolecules. The smoldering experiment revealed that the smoldering front and the evaporation front propagated at stable but different speeds. Among the five fuels, SS4 has the highest smoldering temperature (1070 °C) and the lowest propagation velocity (0.7 cm/min of smoldering velocity and 0.3 cm/min of evaporation velocity), while the carbon density mainly determines the heat release in the oxidation process, and the inorganic elements play a significant catalytic role at different temperatures. The obtained thermodynamic and smoldering characteristics facilitate the development and optimization of the disposal of sewage sludge, emphasizing the importance of considering feedstock composition.
A Mechanistic Study of Methanol Steam Reforming on Ni2P Catalyst
Authors: Almithn Abdulrahman , Alhulaybi Zaid
Published: October 2022

Methanol steam reforming (MSR) is a promising technology for on-board hydrogen production in fuel cell applications. Although traditional Cu-based catalysts demonstrate high catalytic activity and selectivity towards CO2 relative to CO, which is produced via methanol decomposition, they suffer from poor thermal stability and rapid coke formation. Nickel phosphides have been widely investigated in recent years for many different catalytic reactions owing to their remarkable activity and selectivity, as well as their low cost. In this work, we present a mechanistic study of methanol decomposition and MSR pathways on Ni2P using density functional theory (DFT) calculations. DFT-predicted enthalpic barriers indicate that MSR may compete with methanol decomposition on Ni2P, in contrast to other transition metals (e.g., Pt, Pd, and Co) which primarily decompose methanol into CO. The formaldehyde intermediate (CH2O*) can react with co-adsorbed hydroxyl (OH*) from water dissociation to produce H2COOH* which then undergoes subsequent dehydrogenation steps to produce CO2 via H2COOH*→ HCOOH* → HCOO* → CO2. We also examined the conversion of CO into CO2 via the water–gas shift (WGS) reaction, but we ruled out this pathway because it exhibits high activation barriers on Ni2P. These findings suggest that Ni2P is a promising new catalyst for MSR.
Migration Mechanism of Lattice Oxygen: Conversion of CO2 to CO Using NiFe2O4 Spinel Oxygen Carrier in Chemical Looping Reactions
Authors: Song Da , Lin Yan , Zhao Kun , Huang Zhen , He Fang , Xiong Ya
Published: October 2022

CO2 resourceful utilization contributes to the goal of carbon neutrality. Chemical Looping Dry Reforming (CLDR) has attracted significant attention as a method for converting CO2 to CO. NiFe2O4 oxygen carrier (OC) is found to be a potential material for CLDR. However, the migration process of lattice oxygen, which are critical for the conversion of CO2 to CO, was not extensively investigated. In this study, the reduction and oxidation degrees of the NiFe2O4 were finely modulated in a thermogravimetric analyzer. The lattice oxygen migration mechanism of the NiFe2O4 in redox cycles was characterized by means of X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and in-situ Raman. The novelty of this paper is clarifying the release-uptake paths of lattice oxygen during CO2 resourceful utilization. The result indicates that the concentration gradient between the surface and the bulk drives the diffusion of lattice oxygen. The stabilization of surface lattice oxygen content is attributed to the rapid migration of O anion, which is closely associated with the movement process of Ni particles inward and outward through the spinel bulk. In addition, a highly reactive chemical reaction interface consisting of lattice oxygen and the corresponding metal atoms is always present on the surface of the oxygen carrier and is confirmed by an in-situ Raman and XPS during the whole process of CLDR. The results of this paper offer reference and basis for further development and design of CLDR using spinel OC.
Effect of the Active Metal on the NOx Formation during Catalytic Combustion of Ammonia SOFC Off-Gas
Authors: Weissenberger Tobias , Zapf Ralf , Pennemann Helmut , Kolb Gunther
Published: October 2022

Catalytic combustion of hydrogen and ammonia containing off-gas surrogate from an ammonia solid oxide fuel cell (SOFC) was studied with a focus on nitrogen oxides (NOx) mitigation. Noble and transition metals (Pt, Pd, Ir, Ru, Rh, Cu, Fe, Ni) supported on Al2O3 were tested in the range of 100 to 800 °C. The tested catalysts were able to completely convert hydrogen and ammonia present in the off-gas. The selectivity to NOx increased with reaction temperature and stagnated at temperatures of 600 °C and higher. At low temperatures, the formation of N2O was evident, which declined with increasing temperature until no N2O was observed at temperatures exceeding 400 °C. Over nickel and iridium-based catalysts, the NOx formation was reduced drastically, especially at 300 to 400 °C. To the best knowledge of the authors, the current paper is the first study about catalytic combustion of hydrogen-ammonia mixtures as a surrogate of an ammonia-fed SOFC off-gas.
Fluoride-Doped TiO2 Photocatalyst with Enhanced Activity for Stable Pollutant Degradation
Authors: Díez Aida M. , Núñez Iván , Pazos Marta , Sanromán M. Ángeles , Kolen’ko Yury V.
Published: October 2022

Fluoride-doped TiO2 (F-TiO2) was synthesized by an efficient and simple one-step synthesis and successfully used for the UV-photo-degradation of the toxic and stable pollutants methylene blue (MB) and bisphenol A (BPA). Initially, the synthesized catalyst was characterized and compared to untreated TiO2 (P25 Degussa) by different physical–chemical analyses such as XRD, band gap calculation, SEM, EDS, FITR, ECSA, or EIS. F-TiO2 defeated commercial TiO2, and almost complete pollutant removal was achieved within 30 min. The energy consumption was reduced as a result of the suitable reactor set-up, which reduced light scattering, and by the application of a long-pulse radiation procedure, where the lamp was switched off during periods where the radical degradation continued. This enhanced the overall photocatalysis process performance. Under these conditions, 80% of MB removal was attained within 15 min radiation with an energy consumption of only 0.070 Wh min−1, demonstrating a much better efficiency when compared to previously reported data. The catalyst was reusable, and its performance can be improved by the addition of H2O2. The results were validated by BPA degradation and the treatment of real wastewaters with both pollutants. The results were so encouraging that a scale-up reactor has been proposed for future studies.
Calcium-Sensing Receptor (CaSR)-Mediated Intracellular Communication in Cardiovascular Diseases
Authors: Chu Hezhen , Qin Zhenqian , Ma Jun , Xie Yimin , Shi Haifeng , Gu Jie , Shi Baiqiang
Published: October 2022

The calcium-sensing receptor (CaSR), a G-protein-coupled receptor (GPCR), is a cell-surface-located receptor that can induce highly diffusible messengers (IP3, Ca2+, cAMP) in the cytoplasm to activate various cellular responses. Recently, it has also been suggested that the CaSR mediates the intracellular communications between the endoplasmic reticulum (ER), mitochondria, nucleus, protease/proteasome, and autophagy–lysosome, which are involved in related cardiovascular diseases. The complex intracellular signaling of this receptor challenges it as a valuable therapeutic target. It is, therefore, necessary to understand the mechanisms behind the signaling characteristics of this receptor in intracellular communication. This review provides an overview of the recent research progress on the various regulatory mechanisms of the CaSR in related cardiovascular diseases and the heart–kidney interaction; the associated common causes are also discussed.
Baicalin Modulates Inflammatory Response of Macrophages Activated by LPS via Calcium-CHOP Pathway
Authors: An Hyo-Jin , Lee Ji-Young , Park Wansu
Published: October 2022

Studies on natural products that can alleviate the inflammatory response of macrophages caused by endotoxin (lipopolysaccharide) continue. This study investigated the anti-inflammatory activity of baicalin related to macrophage activation caused by lipopolysaccharide (LPS). Baicalin is a flavone glycoside found in plants such as Scutellaria baicalensis and Scutellaria lateriflora belonging to the genus Scutellaria. The multiplex cytokine assay (MCA), Griess reagent assay, fluo-4 calcium assay, dihydrorhodamine 123 (DHR123) assay, quantitative RT-PCR, and flow cytometry were performed using RAW 264.7 mouse macrophages. The MCA revealed that baicalin significantly decreased the production of interleukin (IL)-6, granulocyte colony-stimulating factor (G-CSF), vascular endothelial growth factor (VEGF), macrophage inflammatory protein (MIP)-1α, MIP-1β, MIP-2, and RANTES in LPS-stimulated RAW 264.7 macrophages at concentrations of 10, 25, and 50 μM. The DHR123 assay showed that baicalin significantly inhibited reactive oxygen species generation in LPS-stimulated RAW 264.7 macrophages. Flow cytometry revealed that baicalin significantly reduced the levels of phosphorylated p38 MAPK and Fas in LPS-stimulated RAW 264.7 macrophages. Baicalin also inhibited the mRNA expression levels of inflammatory genes such as Chop, Fas, Nos2, Ptgs2, Stat1, c-Jun, c-Fos, and At1a. The IC50 values of baicalin for IL-6, TNF-α, G-CSF, VEGF, interferon gamma-induced protein 10 (IP-10), leukemia inhibitory factor (LIF), lipopolysaccharide-induced CXC chemokine (LIX), MIP-1α, MIP-1β, MIP-2, RANTES, nitric oxide, intracellular calcium, and hydrogen peroxide were 591.3, 450, 1719, 27.68, 369.4, 256.6, 230.7, 856.9, 1326, 1524, 378.1, 26.76, 345.1, and 32.95 μM, respectively. Baicalin modulated the inflammatory response of macrophages activated by LPS via the calcium-CHOP pathway.
Technologies Enabling Single-Molecule Super-Resolution Imaging of mRNA
Authors: Tingey Mark , Schnell Steven J. , Yu Wenlan , Saredy Jason , Junod Samuel , Patel Dhrumil , Alkurdi Abdullah A. , Yang Weidong
Published: October 2022

The transient nature of RNA has rendered it one of the more difficult biological targets for imaging. This difficulty stems both from the physical properties of RNA as well as the temporal constraints associated therewith. These concerns are further complicated by the difficulty in imaging endogenous RNA within a cell that has been transfected with a target sequence. These concerns, combined with traditional concerns associated with super-resolution light microscopy has made the imaging of this critical target difficult. Recent advances have provided researchers the tools to image endogenous RNA in live cells at both the cellular and single-molecule level. Here, we review techniques used for labeling and imaging RNA with special emphases on various labeling methods and a virtual 3D super-resolution imaging technique.