Syncope and Brugada-Like ECG Pattern in a Patient with Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH).

Syncope is a brief loss of consciousness caused by reduced blood flow to the brain, characterised by sudden onset, short duration and full recovery without intervention. Anamnesis, physical examination and other diagnostic tests such as laboratory analysis and electrocardiogram (ECG) can be conducted to identify the underlying cause of syncope. A Brugada pattern on an ECG in individuals with syndrome of inappropriate antidiuretic hormone secretion (SIADH) who have syncope symptoms may indicate cardiac issues. A 69-year-old man with hypertension and a history of smoking presented with syncope. His vital signs were within normal limits, with no signs of a neurological deficit. The patient met the diagnostic criteria for SIADH, as evidenced by the presence of hyponatraemia (Na 118 mmol/l), a hyperosmolar condition and euvolemia. Upon arrival, a twelve-lead ECG showed ST-segment anomalies that reflected a Brugada ECG pattern. No ventricular arrhythmias were detected during the 24-hour Holter monitoring. Coronary angiography revealed no abnormalities in the coronary arteries. The ECG demonstrated the normalisation of ST elevations and the disappearance of the Brugada ECG pattern after the correction of hyponatraemia. After three months of follow-up the patient, with a normal sodium level, had no episodes of syncope. LEARNING POINTS: Syncope in elderly patients with Brugada-like ECG patterns can arise from cardiac causes, thus necessitating more examinations.Severe hyponatraemia in patients with SIADH can cause syncope and a Brugada-like ECG pattern.Correction of hyponatraemia, after ruling out cardiac causes, can improve syncope and normalise the Brugada-like ECG pattern.

Corrigendum: Sesquiterpene lactones attenuate paclitaxel resistance via inhibiting MALAT1/STAT3/ FUT4 axis and P-Glycoprotein transporters in lung cancer cells.

[This corrects the article DOI: 10.3389/fphar.2022.795613.].

Ferroptosis and the ubiquitin-proteasome system: exploring treatment targets in cancer.

Ferroptosis is an emerging mode of programmed cell death fueled by iron buildup and lipid peroxidation. Recent evidence points to the function of ferroptosis in the aetiology and development of cancer and other disorders. Consequently, harnessing iron death for disease treatment has diverted the interest of the researchers in the field of basic and clinical research. The ubiquitin-proteasome system (UPS) represents a primary protein degradation pathway in eukaryotes. It involves labelling proteins to be degraded by ubiquitin (Ub), followed by recognition and degradation by the proteasome. Dysfunction of the UPS can contribute to diverse pathological processes, emphasizing the importance of maintaining organismal homeostasis. The regulation of protein stability is a critical component of the intricate molecular mechanism underlying iron death. Moreover, the intricate involvement of the UPS in regulating iron death-related molecules and signaling pathways, providing valuable insights for targeted treatment strategies. Besides, it highlights the potential of ferroptosis as a promising target for cancer therapy, emphasizing the combination between ferroptosis and the UPS. The molecular mechanisms underlying ferroptosis, including key regulators such as glutathione peroxidase 4 (GPX4), cysteine/glutamate transporter (system XC-), and iron metabolism, are thoroughly examined, alongside the role of the UPS in modulating the abundance and activity of crucial proteins for ferroptotic cell death, such as GPX4, and nuclear factor erythroid 2-related factor 2 (NRF2). As a pivotal regulatory system for macromolecular homeostasis, the UPS substantially impacts ferroptosis by directly or indirectly modulating iron death-related molecules or associated signaling pathways. This review explores the involvement of the UPS in regulating iron death-related molecules and signaling pathways, providing valuable insights for the targeted treatment of diseases associated with ferroptosis.

Hemophilia Healing with AAV: Navigating the Frontier of Gene Therapy.

Gene therapy for hemophilia has advanced tremendously after thirty years of continual study and development. Advancements in medical science have facilitated attaining normal levels of Factor VIII (FVIII) or Factor IX (FIX) in individuals with haemophilia, thereby offering the potential for their complete recovery. Despite the notable advancements in various countries, there is significant scope for further enhancement in haemophilia gene therapy. Adeno-associated virus (AAV) currently serves as the primary vehicle for gene therapy in clinical trials targeting haemophilia. Subsequent investigations will prioritize enhancing viral capsid structures, transgene compositions, and promoters to achieve heightened transduction efficacy, diminished immunogenicity, and more predictable therapeutic results. The present study indicates that whereas animal models have transduction efficiency that is over 100% high, human hepatocytes are unable to express clotting factors and transduction efficiency to comparable levels. According to the current study, achieving high transduction efficiency and high levels of clotting factor expression in human hepatocytes is still insufficient. It is also crucial to reduce the risk of cellular stress caused by protein overload. Despite encountering various hurdles, the field of haemophilia gene therapy holds promise for the future. As technology continues to advance and mature, it is anticipated that a personalized therapeutic approach will be developed to cure haemophilia effectively.

Elevated 2-oxoglutarate antagonizes DNA damage responses in cholangiocarcinoma chemotherapy through regulating aspartate beta-hydroxylase.

Cholangiocarcinoma (CCA) is resistant to systemic chemotherapies that kill malignant cells mainly through DNA damage responses (DDRs). Recent studies suggest that the involvement of 2-oxoglutarate (2-OG) dependent dioxygenases in DDRs may be associated with chemoresistance in malignancy, but how 2-OG impacts DDRs in CCA chemotherapy remains elusive. We examined serum 2-OG levels in CCA patients before receiving chemotherapy. CCA patients are classified as progressive disease (PD), partial response (PR), and stable disease (SD) after receiving chemotherapy. CCA patients classified as PD showed significantly higher serum 2-OG levels than those defined as SD and PR. Treating CCA cells with 2-OG reduced DDRs. Overexpression of full-length aspartate beta-hydroxylase (ASPH) could mimic the effects of 2-OG on DDRs, suggesting the important role of ASPH in chemoresistance. Indeed, the knockdown of ASPH improved chemotherapy in CCA cells. Targeting ASPH with a specific small molecule inhibitor also enhanced the effects of chemotherapy. Mechanistically, ASPH modulates DDRs by affecting ATM and ATR, two of the major regulators finely controlling DDRs. More importantly, targeting ASPH improved the therapeutic potential of chemotherapy in two preclinical CCA models. Our data suggested the impacts of elevated 2-OG and ASPH on chemoresistance through antagonizing DDRs. Targeting ASPH may enhance DDRs, improving chemotherapy in CCA patients.

Molecular profiling reveals potential targets in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is a devastating malignancy and has a very poor prognosis if tumors spread outside the liver. Understanding the molecular mechanisms underlying the CCA progression will likely yield therapeutic approaches toward treating this deadly disease. AIM: To determine the molecular pathogenesis in CCA progression. METHODS: In silico analysis, in vitro cell culture, CCA transgenic animals, histological, and molecular assays were adopted to determine the molecular pathogenesis. RESULTS: The transcriptomic data of human CCA samples were retrieved from The Cancer Genome Atlas (TGCA, CHOL), European Bioinformatics Institute (EBI, GAD00001001076), and Gene Expression Omnibus (GEO, GSE107943) databases. Using Gene set enrichment analysis, the cell cycle and Notch related pathways were demonstrated to be significantly activated in CCA in TCGA and GEO datasets. We, through differentially expressed genes, found several cell cycle and notch associated genes were significantly up-regulated in cancer tissues when compared with the non-cancerous control samples. The associated genes, via quantitative real-time PCR and western blotting assays, were further examined in normal human cholangiocytes, CCA cell lines, mouse normal bile ducts, and mouse CCA tumors established by specifically depleting P53 and expressing KrasG12D mutation in the liver. Consistently, we validated that the cell cycle and Notch pathways are up-regulated in CCA cell lines and mouse CCA tumors. Interestingly, targeting cell cycle and notch pathways using small molecules also exhibited significant beneficial effects in controlling tumor malignancy. More importantly, we demonstrated that several cell cycle and Notch associated genes are significantly associated with poor overall survival and disease-free survival using the Log-Rank test. CONCLUSION: In summary, our study comprehensively analyzed the gene expression pattern of CCA samples using publicly available datasets and identified the cell cycle and Notch pathways are potential therapeutic targets in this deadly disease.

TME-targeted approaches of brain metastases and its clinical therapeutic evidence.

The tumor microenvironment (TME), which includes both cellular and non-cellular elements, is now recognized as one of the major regulators of the development of primary tumors, the metastasis of which occurs to specific organs, and the response to therapy. Development of immunotherapy and targeted therapies have increased knowledge of cancer-related inflammation Since the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCB) limit immune cells from entering from the periphery, it has long been considered an immunological refuge. Thus, tumor cells that make their way "to the brain were believed to be protected from the body's normal mechanisms of monitoring and eliminating them. In this process, the microenvironment and tumor cells at different stages interact and depend on each other to form the basis of the evolution of tumor brain metastases. This paper focuses on the pathogenesis, microenvironmental changes, and new treatment methods of different types of brain metastases. Through the systematic review and summary from macro to micro, the occurrence and development rules and key driving factors of the disease are revealed, and the clinical precision medicine of brain metastases is comprehensively promoted. Recent research has shed light on the potential of TME-targeted and potential treatments for treating Brain metastases, and we'll use that knowledge to discuss the advantages and disadvantages of these approaches.

Role of LGMN in tumor development and its progression and connection with the tumor microenvironment.

Legumain (LGMN) has been demonstrated to be overexpressed not just in breast, prostatic, and liver tumor cells, but also in the macrophages that compose the tumor microenvironment. This supports the idea that LGMN is a pivotal protein in regulating tumor development, invasion, and dissemination. Targeting LGMN with siRNA or chemotherapeutic medicines and peptides can suppress cancer cell proliferation in culture and reduce tumor growth in vivo. Furthermore, legumain can be used as a marker for cancer detection and targeting due to its expression being significantly lower in normal cells compared to tumors or tumor-associated macrophages (TAMs). Tumor formation is influenced by aberrant expression of proteins and alterations in cellular architecture, but the tumor microenvironment is a crucial deciding factor. Legumain (LGMN) is an in vivo-active cysteine protease that catalyzes the degradation of numerous proteins. Its precise biological mechanism encompasses a number of routes, including effects on tumor-associated macrophage and neovascular endothelium in the tumor microenvironment. The purpose of this work is to establish a rationale for thoroughly investigating the function of LGMN in the tumor microenvironment and discovering novel tumor early diagnosis markers and therapeutic targets by reviewing the function of LGMN in tumor genesis and progression and its relationship with tumor milieu.

Genome-wide characterization and sequence polymorphism analyses of cysteine-rich poly comb-like protein in Glycine max.

Cysteine-rich poly comb-like protein (CPP) is a member of cysteine-rich transcription factors that regulates plant growth and development. In the present work, we characterized twelve CPP transcription factors encoding genes in soybean (Glycine max). Phylogenetic analyses classified CPP genes into six clades. Sequence logos analyses between G. max and G. soja amino acid residues exhibited high conservation. The presence of growth and stress-related cis-acting elements in the upstream regions of GmCPPs highlight their role in plant development and tolerance against abiotic stress. Ka/Ks levels showed that GmCPPs experienced limited selection pressure with limited functional divergence arising from segmental or whole genome duplication events. By using the PAN-genome of soybean, a single nucleotide polymorphism was identified in GmCPP-6. To perform high throughput genotyping, a kompetitive allele-specific PCR (KASP) marker was developed. Association analyses indicated that GmCPP-6-T allele of GmCPP-6 (in exon region) was associated with higher thousand seed weight under both water regimes (well-water and water-limited). Taken together, these results provide vital information to further decipher the biological functions of CPP genes in soybean molecular breeding.

A high-performance, hardware-based deep learning system for disease diagnosis.

Modern deep learning schemes have shown human-level performance in the area of medical science. However, the implementation of deep learning algorithms on dedicated hardware remains a challenging task because modern algorithms and neuronal activation functions are generally not hardware-friendly and require a lot of resources. Recently, researchers have come up with some hardware-friendly activation functions that can yield high throughput and high accuracy at the same time. In this context, we propose a hardware-based neural network that can predict the presence of cancer in humans with 98.23% accuracy. This is done by making use of cost-efficient, highly accurate activation functions, Sqish and LogSQNL. Due to its inherently parallel components, the system can classify a given sample in just one clock cycle, i.e., 15.75 nanoseconds. Though this system is dedicated to cancer diagnosis, it can predict the presence of many other diseases such as those of the heart. This is because the system is reconfigurable and can be programmed to classify any sample into one of two classes. The proposed hardware system requires about 983 slice registers, 2,655 slice look-up tables, and only 1.1 kilobits of on-chip memory. The system can predict about 63.5 million cancer samples in a second and can perform about 20 giga-operations per second. The proposed system is about 5-16 times cheaper and at least four times speedier than other dedicated hardware systems using neural networks for classification tasks.

Medicinal waterbirds in the traditional healthcare system: an assessment of biodiversity-cultural linkages in Eastern Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Eastern Khyber Pakhtunkhwa is home to a vast range of medicinal and edible waterbird species due to its diverse geographical environment. Waterbird species have been used for various ailments and cultural practices since ancient times, while ethno-pharmacological applications and cultural uses of waterbird species in this area have seldom been documented. This study is the first ethnomedicinal and cultural assessment of waterbird species, and the first compilation and listing of all known data on these species in Eastern Khyber Pakhtunkhwa, Pakistan. METHODS: Interviews and questionnaires were used to collect data from native respondents (N = 100). To analyze the data, principal component analysis (PCA), relative frequency of citation (RFC), fidelity level (FL%), relative popularity level (RPL), rank order priority, and similarity index were used. RESULTS: In total, 64 waterbird species were utilized in cultural practices, of which 40 species are used to cure different infectious and chronic diseases such as cold, cough, flu, fever, respiratory disorders, asthma, TB, gastric ulcers, kidney stones, male impotency, obesity, paralysis, piles, cancer, arthritis, body pain, and weakness. PCA showed significant differences in the use of waterbird species among the local inhabitants of the study area, separated along the axis-2 (p < 0.05). The FL% of waterbird species varied from 12 to 100%. 100% FL was analyzed for four waterbird species, i.e., Charadrius mongolus (cold), Gallicrex cinerea (asthma), Anas platyrhynchos (cancer), and Esacus recurvirostris (body weakness). In this study, Mallard (Anas platyrhynchos) was the most popular species used in the healthcare system of Eastern Khyber Pakhtunkhwa, with high RFC (4.06), FL% (100), and RPL (1.0) values. CONCLUSION: We concluded that waterbird species are more used for medicine and food purposes in the study area. However, in vitro/in vivo assessment of biochemical activities of waterbird species with a maximum FL% might be significant to produce novel drugs. Recent research shows important ethno-ornithological information about native people and their links with waterbird species, which might be helpful for the sustainable use of waterbird diversity in the research area.

Black phosphorus nanosheets/poly(allylamine hydrochloride) based electrochemical immunosensor for the selective detection of human epididymis protein 4.

In this work, an electrochemical immunosensor based on black phosphorus nanosheets (BPNS)/poly(allylamine hydrochloride) (PAH) nanocomposite modified glassy carbon electrode was developed for the detection of ovarian cancer biomarker HE4. PAH has been applied to retain BPNS in its original honeycomb structure and to anchor biomolecules electrostatically on the transducer surface. The as synthesized nanocomposite was characterized by zeta potential analysis, scanning electron microscopy, x-ray photoelectron spectroscopy, transmission electron microscopy, high-resolution transmission electron microscopy. Subsequently, the performance of the electrochemical immunosensor was evaluated through cyclic voltammetry, differential pulse voltammetry and electrochemical impedance spectroscopy. Under the optimal condition, the developed electrochemical immunosensor permitted to detect HE4 with a linear range of 0.1-300 ng ml-1and a detection limit of 0.01 ng ml-1. The developed sensor exhibited good selectivity and specificity to HE4 with negligible interference effect from common biomolecules like bovine serum albumin, lysozyme, protamine, glucose, fructose, hemoglobin and fetal bovine serum. Further, practical application of developed electrochemical immunosensor was demonstrated in spiked human serum which showed satisfactory recovery percentages.

Polypeptide induced perylene probe excimer formation and its application in the noncovalent ratiometric detection of matrix metalloproteinase activity.

Matrix metalloproteinases (MMPs) are important biomarkers for a number of diseases. Thus, the precise determination of MMP activity is of crucial importance. Herein, we report a ratiometric fluorescence method for the sensitive and selective sensing of MMP activity. A number of positively charged MMP substrates (polypeptides) were designed and prepared. These polypeptides could induce aggregation of a negatively charged perylene diimide derivative (PC1). As a result, excimer fluorescence of PC1 was observed. Addition of the corresponding MMP resulted in cleavage of the polypeptide chain and dis-aggregation of PC1, which led to turning on of the PC1 monomer fluorescence. Based on the ratio of the monomer (545 nm, IM) and the excimer (680 nm, IM) fluorescence intensity changes, a ratiometric method I545/I680) was established to detect MMP activity. The enzymatic activity of a number of MMPs (MMP-1, 2, 3, 7, 9 and 13) could be determined with a limit of detection of 4.8, 2.2, 16, 6.0, 1.7 and 5.5 ng mL-1, respectively. Using MMP-2 and MMP-9 as examples, flavonoid herbal extracts as potential inhibitors were studied. It was observed that mangiferin, apigenin, quercetin and isoliquiritigenin had significant inhibiting effects on the enzyme activity. And these herbal extracts also inhibited tumor cell metastasis. Moreover, the developed strategy was also employed to determine the concentration of MMP-9 in human saliva samples. Since the method relies on only noncovalent interactions between the polypeptide and PC1, no covalent labeling of fluorescence dye on the polypeptide substrate is required, and the method is thus simple, broad-spectrum inexpensive and effective. It has the potential to be developed into a clinical test kit.

Ca2+/Calmodulin-Dependent Protein Kinase II Inhibits Hepatitis B Virus Replication from cccDNA via AMPK Activation and AKT/mTOR Suppression.

Ca2+/calmodulin-dependent protein kinase II (CaMKII), which is involved in the calcium signaling pathway, is an important regulator of cancer cell proliferation, motility, growth, and metastasis. The effects of CaMKII on hepatitis B virus (HBV) replication have never been evaluated. Here, we found that phosphorylated, active CaMKII is reduced during HBV replication. Similar to other members of the AMPK/AKT/mTOR signaling pathway associated with HBV replication, CaMKII, which is associated with this pathway, was found to be a novel regulator of HBV replication. Overexpression of CaMKII reduced the expression of covalently closed circular DNA (cccDNA), HBV RNAs, and replicative intermediate (RI) DNAs while activating AMPK and inhibiting the AKT/mTOR signaling pathway. Findings in HBx-deficient mutant-transfected HepG2 cells showed that the CaMKII-mediated AMPK/AKT/mTOR signaling pathway was independent of HBx. Moreover, AMPK overexpression reduced HBV cccDNA, RNAs, and RI DNAs through CaMKII activation. Although AMPK acts downstream of CaMKII, AMPK overexpression altered CaMKII phosphorylation, suggesting that CaMKII and AMPK form a positive feedback loop. These results demonstrate that HBV replication suppresses CaMKII activity, and that CaMKII upregulation suppresses HBV replication from cccDNA via AMPK and the AKT/mTOR signaling pathway. Thus, activation or overexpression of CaMKII may be a new therapeutic target against HBV infection.

Sesquiterpene Lactones Attenuate Paclitaxel Resistance Via Inhibiting MALAT1/STAT3/ FUT4 Axis and P-Glycoprotein Transporters in Lung Cancer Cells.

Paclitaxel resistance is a challenging factor in chemotherapy resulting in poor prognosis and cancer recurrence. Signal transducer and activator of transcription factor 3 (STAT3), a key transcription factor, performs a critical role in cancer development, cell survival and chemoresistance, while its inactivation overwhelms drug resistance in numerous cancer types including lung cancer. Additionally, the fucosyltransferase 4 (FUT4) is a crucial enzyme in post-translational modification of cell-surface proteins involved in various pathological conditions such as tumor multidrug resistance (MDR). The P-glycoprotein (P-GP) is the well-known ABC transporter member that imparts drug resistance in different cancer types, most notably paclitaxel resistance in lung cancer cells. LncRNA-MALAT1 exerts a functional role in the cancer development as well as the drug resistance and is linked with STAT3 activation and activity of FUT4. Moreover, STAT3-mediated induction of P-GP is well-documented. Natural compounds of Sesquiterpene Lactone (SL) family are well-known for their anticancer properties with particular emphasis over STAT3 inhibitory capabilities. In this study, we explored the positive correlation of MALAT1 with STAT3 and FUT4 activity in paclitaxel resistant A549 (A549/T) lung cancer cells. Additionally, we investigated the anticancer activity of two well-known members of SLs, alantolactone (ALT) and Brevilin A (Brv-A), in A549/T lung cancer cells. ALT and Brv-A induced apoptosis in A549/T cells. Furthermore, these two natural SLs suppressed MALAT1 expression, STAT3 activation, and FUT4 and P-GP expression which are the hallmarks for paclitaxel resistance in A549 lung cancer cells. The inhibition of MALAT1 enhanced the competence of these SLs members significantly, which accounted for the growth inhibition as well as anti-migratory and anti-invasive effects of ALT and Brv-A. These findings suggest SLs to be the promising agents for overcoming paclitaxel resistance in A549 lung cancer cells.

Inoculation of Azospirillum brasilense and exogenous application of trans-zeatin riboside alleviates arsenic induced physiological damages in wheat (Triticum aestivum).

Due to increased industrialization, arsenic (As) in the soil has become a serious issue for wheat production since past few decades. We investigated the role of Azospirillum brasilense and trans-zeatin riboside (tZR) in the mitigation of arsenic toxicity in wheat for 2 years (2018-2019 and 2019-2020) in pot experiments. Wheat plants grown in soil artificially spiked with arsenic (50, 70, and 100 µM) was left alone or amended with A. brasilense, tZR, or their combination as mitigation strategies. A treatment without arsenic or amendments was maintained as control. Arsenic-induced physiological damages were noticed in the wheat plants. Detrimental effects on the plant physiological functions, such as disruption of cell membrane stability, reduced water uptake, and stomatal functions, were noticed with increase in As toxicity. Application of biological amendments reversed the effects of As toxicity by increasing wheat plant growth rate, leaf area, and photosynthesis and also yield. Therefore, application of tZR and wheat seed inoculation with A. brasilense could be a sustainable and environmentally friendly strategy to mitigate arsenic-induced crop physiological damages.

Seasonal Fluctuations of N, P and K in Leaves Influenced Nutrient Requirement During Fruit Development Stages in Different Olive Genotypes

Abstract: Olive is grown in semi-arid climatic conditions; however, little is known about mineral changes in olive plant and nutrient requirements during the production period. Hence, the current study was conducted under Pothwar agro-climatic conditions in order to select appropriate stage of macronutrients (N, P, K) application in relation to soil and leaf nutritional status during 2017 and 2018 growing seasons. Soil and leaf analysis were performed at four different phenological stages (i.e. flowering, fruit setting, fruit enlargement and fruit maturity stages). The results revealed that the assessed macronutrient in leaf and soil varied significantly among varieties, phenological stages and growing year. The results revealed also that nitrogen level was found to decrease from fruit set (1.56%) to fruit enlargement stage (1.47%). Leaf and soil N, P and K contents were found higher before the flowering (stage 1) and depleted after fruit harvesting (stage 4), regardless of olive varieties. However, high yielding varieties showed lower nutrients after fruit harvesting (stage 4). Therefore, N content in leaf and soil gradually decreased during fruit growth and development. Whereas, K content in leaf and soil sharply declined from fruit maturity to fruit ripening stage. Overall, the trend of nutrient depletion showed that plants need phosphorus for fruit setting, nitrogen before and after fruit setting, and potash after pit hardening or at oil accumulation stages.

Latcripin-7A from Lentinula edodes C91-3 induces apoptosis, autophagy, and cell cycle arrest at G1 phase in human gastric cancer cells via inhibiting PI3K/Akt/mTOR signaling.

Gastric cancer (G.C) is one of the most lethal cancer types worldwide. Current treatment requires surgery along with chemotherapy, which causes obstacles for speedy recovery. The discovery of novel drugs is needed for better treatment of G.C with minimum side effects. Latcripin-7A (LP-7A) is a newly discovered peptide extracted from Lentinula edodes. It is recently studied for its anti-cancer activity. In this study, LP-7A was modeled using a phyre2 server. Anti-proliferation effects of LP-7A on G.C cells were examined via CCK-8, colony formation, and morphology assay. Apoptosis of LP-7A treated G.C cells was evaluated via Hoechst Stain, western blot and flow cytometry. Autophagy was assessed via acridine orange staining and western blot. The cell cycle was assessed via flow cytometry assay and western blot. Pathway was studied via western blot and STRING database. Anti-migratory effects of LP-7A treated G.C cells were analyzed via wound healing, western blot, and migration and invasion assay. LP-7A effectively inhibited the growth of G.C cells by inhibiting the PI3K/Akt/mTOR pathway. G.C cells treated with LP-7A arrested the cell cycle at the G1 phase, contributing to the inhibition of migration and invasion. Furthermore, LP-7A induced apoptosis and autophagy in gastric cancer cells. These results indicated that LP-7A is a promising anti-cancer agent. It affected the proliferation and growth of G.C cells (SGC-7901 and BGC-823) by inducing apoptosis, autophagy, and inhibiting cell cycle at the G1 phase in G.C cells.

Financial development, oil resources, and environmental degradation in pandemic recession: to go down in flames.

The novel coronavirus disease-2019 (COVID-19) is a deadly disease that increases global healthcare sufferings. Further, it affects the financial and natural resource market simultaneously, as both are considered complementary goods. The volatility in the oil prices deteriorates the global financial market to substantiate the "financial resource (oil) curse" hypothesis primarily filled with earlier studies. In contrast, this study moved forward and extended the given relationship during the COVID-19 pandemic in a panel of 81 different countries. The study's main objective is to examine the volatility in the domestic credit provided to the private sector due to oil shocks and the COVID-19 pandemic across countries. The study is essential to assess the healthcare vulnerability in the COVID-19 pandemic, leading to the damage of financial stability, causing deterioration in the oil rents to affect the global sustainability agenda. The study employed statistical techniques to get sound inferences of the parameter estimates, including robust least squares regression, seemingly unrelated regression, and innovation accounting matrix to get a variable estimate at the level and inter-temporal framework. The results confirmed the U-shaped relationship between oil rents and financial development during the COVID-19 pandemic. Thus, it verifies the "financial resource (oil) curse" hypothesis at the initial stage of the COVID-19 pandemic. Later down, it supports the capital market when economies are resuming their economic activities and maintaining the SOPs to restrain coronavirus at a global scale. The qualitative assessment confirmed the negative effect of financial development and oil shocks on environmental quality during the pandemic crisis. The innovation accounting matrix shows that the COVID-19 pandemic will primarily be the main factor that intervenes in the relationship between oil rents and financial development, which proceed towards the "resource curse" hypothesis during the following years' time period. Therefore, the need for long-term economic policies is highly desirable to support the financial and resource market under the suggested guidelines of restraining coronavirus worldwide.

IL-1ß Promotes Vasculogenic Mimicry of Breast Cancer Cells Through p38/MAPK and PI3K/Akt Signaling Pathways.

Vasculogenic mimicry (VM), a micro vessel-like structure formed by the cancer cells, plays a pivotal role in cancer malignancy and progression. Interleukin-1 beta (IL-1ß) is an active pro-inflammatory cytokine and elevated in many tumor types, including breast cancer. However, the effect of IL-1ß on the VM of breast cancer has not been clearly elucidated. In this study, breast cancer cells (MCF-7 and MDA-MB-231) were used to study the effect of IL-1ß on the changes that can promote VM. The evidence for VM stimulated by IL-1ß was acquired by analyzing the expression of VM-associated biomarkers (VE-cadherin, VEGFR-1, MMP-9, MMP-2, c-Fos, and c-Jun) via western blot, immunofluorescent staining, and Immunohistochemistry (IHC). Additionally, morphological evidence was collected via Matrigel-based cord formation assay under normoxic/hypoxic conditions and microvessel examination through Hematoxylin and Eosin staining (H&E). Furthermore, the STRING and Gene Ontology database was also used to analyze the VM-associated interacting molecules stimulated by IL-ß. The results showed that the expression of VM biomarkers was increased in both MCF-7 and MDA-MB-231 cells after IL-1ß treatment. The increase in VM response was observed in IL-1ß treated cells under both normoxia and hypoxia. IL-1ß also increased the activation of transcription factor AP-1 complex (c-Fos/c-Jun). The bioinformatics data indicated that p38/MAPK and PI3K/Akt signaling pathways were involved in the IL-1ß stimulation. It was further confirmed by the downregulated expression of VM biomarkers and reduced formation of the intersections upon the addition of the signaling pathway inhibitors. The study suggests that IL-1ß stimulates the VM and its associated events in breast cancer cells via p38/MAPK and PI3K/Akt signaling pathways. Aiming the VM-associated molecular targets promoted by IL-1ß may offer a novel anti-angiogenic therapeutic strategy to control the aggressiveness of breast cancer cells.