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Geopolymer materials have excellent properties such as high strength, low thermal conductivity, fire resistance, acid and alkali resistance, and low carbon emissions. They can be used as protective engineering materials in places with explosion risks. At present, the common composite blast resistant panel is in the form of a sandwich: the outer layer isgalvanized steel plate, and fiber cement board or calcium carbonate board is used as the inner layer material, as these boards have the advantages of easy installation, good fire resistance, and explosion resistance. This study investigates the effect of adding different types of fibers to geopolymer mortar on the mortar's basic mechanical properties, such as compression strength, bending strength, and impact resistance. The explosive resistance of the fiber-reinforced geopolymer mortar blast resistant panels was evaluated through free-air explosion. In this paper, experimental procedures and numerical simulation have been performed to study the failure modes, maximum deflection, and dynamic response of the fiber-reinforced geopolymer mortar blast resistant panel under free-air explosion. The research results can provide a reference for the design and production of blast resistant panels. [ABSTRACT FROM AUTHOR]

Rhipicephalus microplus is a major bovine ectoparasite that negatively impacts the cattle industry. The acaricidal activity of Datura innoxia ethanolic plant extract against R. microplus, compared with trichlorfon, was examined using the adult immersion test (AIT), and larval packet test (LPT). In vitro acaricidal activity of the selected plant extract against R. microplus engorged females was evaluated at different concentrations (2.5, 5, 10, 20, and 40 mg/mL), and was the same for AIT and LPT. It was further supported by in silico molecular docking of D. innoxia's 21 phytochemicals against the R. microplus Glutathione S-transferases (RmGST) protein's three-dimensional (3D) structure predicted by the trRosetta server. The modeled 3D structure was then evaluated and confirmed with PROCHECK, ERRAT, and Verify3D online servers. To predict the binding mechanisms of these compounds, molecular docking was performed using Auto dock Vina software, and molecular dynamic (MD) simulations were used to investigate the protein atom's dynamic motion. D. innoxia has a relatively higher inhibitory effect on oviposition (from 9.81% to 45.37%) and total larval mortality (42.33% at 24 h and 93.67% at 48 h) at 40 mg/mL. Moreover, the docking results showed that the chemicals norapoatropine and 7-Hydroxyhyoscyamine have strong interactions with active site residues of the target protein, with a docking score of −7.3 and −7.0 Kcal/mol, respectively. The current work also provided a computational basis for the inhibitors of Glutathione S-transferases that were studied in this research work, and this new knowledge should aid in creating new and effective acaricidal chemicals. Furthermore, this plant extract's acaricide activity and its effect on oviposition and larval mortality were established in this work for the first time, indicating the possible use of this extract in the management of ticks. [ABSTRACT FROM AUTHOR]

A topic is usually associated with a specific time, place, and person(s). Generally, topics that involve bipolar or competing viewpoints are attention getting and are thus reported in a large number of documents. Identifying the association between important persons mentioned in numerous topic documents would help readers comprehend topics more easily. In this paper, we propose an unsupervised approach for identifying bipolar person names in a set of topic documents. Specifically, we employ principal component analysis (PCA) to discover bipolar word usage patterns of person names in the documents, and show that the signs of the entries in the principal eigenvector of PCA partition the person names into bipolar groups spontaneously. To reduce the effect of data sparseness, we introduce two techniques, called the weighted correlation coefficient and off-topic block elimination. We also present a timeline system that shows the intensity and activeness development of the identified bipolar person groups. Empirical evaluations demonstrate the efficacy of the proposed approach in identifying bipolar person names in topic documents, while the generated timelines provide comprehensive storylines of topics. [ABSTRACT FROM PUBLISHER]

Epicuticular wax, the first protective film for numerous ground plant species, is crucial for modulating the evolution in plants. Since the waxy film is inherently thermoresponsive, many efforts focus on engineering materials for water/oil proofing, delivery, and collection, as well as microactuators by mimicking such film nature. Nonetheless, relatively fewer works address the mechanism of how the underlying substrates direct the reconstruction of waxy films while their temperature approaches the melting point. Here, we presented a strategy in which distinct frameworks of molten wax films could be examined among various substrates. Both "waxphobic" and "waxphilic" traits were first unveiled and could be achieved by the hydrophilic (water contact angle (WCA) = 42~82°) and hydrophobic (WCA = 109°) substrates, respectively. A theoretical model, based on experimental results, fluidic dynamics, and balance of surface energy, was developed to elucidate the above findings. Moreover, we demonstrated the above biomimetic epicuticular surface (BeSurface) can be applied for rewritable paper, erasable coding, and rehealable electronics without manual repairing. Remarkably, the healing time can be reduced down to 30 s, and the cycled folding test can be continued up to 500 times. All the new findings present the potentials of the BeSurface to improve the study of rehealable materials. [ABSTRACT FROM AUTHOR]

(1) Background: Accurate preoperative identification of medullary thyroid carcinoma (MTC) is challenging due to a spectrum of cytomorphologic features. However, there is a scarcity of studies describing the cytomorphologic features as seen on fine-needle aspiration (FNA) smears prepared using different staining methods. (2) Methods: We performed a retrospective study on MTC cases with available FNA slides from 13 hospitals distributed across 8 Asia-Pacific countries. The differences in the constitutive cytomorphologic features of MTC with each cytopreparatory method were recorded. A comparative analysis of cytologic characteristics was carried out with appropriate statistical tests. (3) Results: Of a total of 167 MTC samples retrospectively recruited, 148 (88.6%) were interpreted as MTC/suspicious for MTC (S-MTC). The staining methods used were Papanicolaou, hematoxylin-eosin, and Romanowsky stains. Seven out of the eleven cytologic criteria can be readily recognized by all three cytopreparatory methods: high cellularity, cellular pleomorphism, plasmacytoid cells, round cells, dyshesive cells, salt-and-pepper chromatin, and binucleation or multinucleation. An accurate diagnosis was achieved in 125 (84.5%) of the 148 samples whose FNAs exhibited five or more atypical features. Conclusions: The present work is the first study on MTC to compare the morphological differences among the cytologic staining techniques. We investigated the constitutive features and the reliability of diagnostic parameters. A feasible scoring system based upon cytomorphologic data alone is proposed to achieve a high degree of diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Bartonella henselae is a Gram-negative bacterium causing a variety of clinical symptoms, ranging from cat-scratch disease to severe systemic infections, and it is primarily transmitted by infected fleas. Its status as an emerging zoonotic pathogen and its capacity to persist within host erythrocytes and endothelial cells emphasize its clinical significance. Despite progress in understanding its pathogenesis, limited knowledge exists about the virulence factors and regulatory mechanisms specific to the B. henselae strain Houston-1. Exploring these aspects is crucial for targeted therapeutic strategies against this versatile pathogen. Using reverse-vaccinology-based subtractive proteomics, this research aimed to identify the most antigenic proteins for formulating a multi-epitope vaccine against the B. henselae strain Houston-1. One crucial virulent and antigenic protein, the PAS domain-containing sensor histidine kinase protein, was identified. Subsequently, the identification of B-cell and T-cell epitopes for the specified protein was carried out and the evaluated epitopes were checked for their antigenicity, allergenicity, solubility, MHC binding capability, and toxicity. The filtered epitopes were merged using linkers and an adjuvant to create a multi-epitope vaccine construct. The structure was then refined, with 92.3% of amino acids falling within the allowed regions. Docking of the human receptor (TLR4) with the vaccine construct was performed and demonstrated a binding energy of −1047.2 Kcal/mol with more interactions. Molecular dynamic simulations confirmed the stability of this docked complex, emphasizing the conformation and interactions between the molecules. Further experimental validation is necessary to evaluate its effectiveness against B. henselae. [ABSTRACT FROM AUTHOR]

Hydroa vacciniforme (HV) is a rare form of photosensitivity disorder in children and is frequently associated with Epstein–Barr virus (EBV) infection, whereas HV-like lymphoproliferative disorders (HVLPD) describe a spectrum of EBV-associated T-cell or natural killer (NK)-cell lymphoproliferations with HV-like cutaneous manifestations, including EBV-positive HV, atypical HV, and HV-like lymphoma. Classic HV occurs in childhood with papulovesicules on sun-exposed areas, which is usually induced by sunlight and ultraviolet irradiation, and mostly resolves by early adult life. Unlike classic HV, atypical or severe HV manifests itself as recurrent papulovesicular eruptions in sun-exposed and sun-protected areas associated occasionally with facial edema, fever, lymphadenopathy, oculomucosal lesions, gastrointestinal involvement, and hepatosplenomegaly. Notably, atypical or severe HV may progress to EBV-associated systemic T-cell or natural killer (NK)-cell lymphoma after a chronic course. Although rare in the United States and Europe, atypical or severe HV and HV-like lymphoma are predominantly reported in children from Asia and Latin America with high EBV DNA levels, low numbers of NK cells, and T cell clones in the blood. In comparison with the conservative treatment used for patients with classic HV, systemic therapy such as immunomodulatory agents is recommended as the first-line therapy for patients with atypical or severe HV. This review aims to provide an integrated overview of current evidence and knowledge of HV and HVLPD to elucidate the pathophysiology, practical issues, environmental factors, and the impact of EBV infection. [ABSTRACT FROM AUTHOR]

Background: V. canescens Wall, a plant renowned for its ethno-medical properties, was investigated in this study for its antioxidant potential based on its wide therapeutic applications in traditional healthcare systems. The study aimed to assess the antioxidant potential of the plant extract/fractions and to predict the active phytochemicals using computational techniques. Methods: Five fractions were obtained from the crude methanolic extract of Viola canescens, and six concentrations (25, 50, 75, 100, 125, and 150 pg/mL) were prepared for each fraction. The antioxidant activity of these fractions was evaluated using the Tetraoxomolybdate (VI) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. In-silico docking studies and molecular dynamic simulations were conducted to further elucidate the molecular interactions underlying the antioxidant activity. Results: The aqueous extract of V. canescens exhibited significant antioxidant and free radical scavenging activity against DPPH. Additionally, the crude flavonoid extract demonstrated moderate activity with IC50 value of 57.863 pg/mL, indicating potent inhibition of cell growth. In-silico docking studies revealed a strong interaction between emetine and the aromatase protein, suggesting its potential as an antioxidant. Conclusion: The study findings highlight the antioxidant potential of V. canescens extract, indicating its suitability as a source of natural antioxidants. These results suggest its potential application in pharmaceutical preparations aimed at harnessing antioxidant properties for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Simple Summary: Dermacentor ticks have a wide geographic range with an uneven distribution in the globe. They are not scientifically well known because they survive in hard topographic and harsh climatic regions along with elevated mountains. Many mammals serve as a primary host for Dermacentor ticks, like many other tick species. The present study aimed to provide the first morphological and molecular confirmation of Dermacentor marginatus and its related pathogens like Anaplasma marginale and Rickettsia raoultii in Pakistan. In this study, a total of 26 specimens (19 males and 7 females) were collected from goats and morphologically identified. A subset of 18 specimens were subjected for the molecular characterization of ticks and associated pathogen detection. In the BLAST and phylogenetic analyses, D. marginatus and their associated pathogen sequences showed close resemblance with their corresponding species. In the present study, we reported the first genetic characterization of D. marginatus and associated A. marginale and R. raoultii in Pakistan. Due to the difficult access and harsh climate, it is important to investigate the ticks and related pathogens in the northern parts of Pakistan due to their zoonotic threats. Ticks of the genus Dermacentor Koch, 1844 (Acari: Ixodidae) are poorly known systematically due to their habitation in harsh topographic environments and high mountains. Dermacentor ticks are diversely distributed in the Palearctic, Nearctic, and Oriental regions. There is no available information on the occurrence of Dermacentor marginatus in Pakistan; thus, the current investigation aimed the first morphological and molecular confirmation of this species and associated Anaplasma marginale and Rickettsia raoultii. Ticks were collected from goats (Capra hircus) and morphologically identified. Genomic DNA was extracted from 18/26 (69.23%) tick specimens, including 11 males and 7 females (1 unfed and 6 fed females). Extracted DNA was subjected to PCR for the amplification of genetic markers like 16S rDNA and cox1 for ticks, 16S rDNA for Anaplasma spp., and gltA and ompB for Rickettsia spp. A total of 26 D. marginatus ticks composed of 19 males (73.07%) and 7 females (26.9%) [1 (3.84%) unfed and 6 (23.07%) fed females] were collected from goats. According to amplicons via BLAST analysis, the 16S rDNA sequence showed 97.28–98.85% identity and the cox1 sequence showed 95.82–98.03% identity with D. marginatus. Additionally, the 16S rDNA sequence for Anaplasma sp. was detected in D. marginatus that showed 100% identity with Anaplasma marginale. Rickettsial gltA and ompB sequences for Rickettsia sp. showed 100% identity with Rickettsia raoultii. In phylogenetic analysis, ticks' 16S rDNA and cox1 sequences clustered with the same species. In phylogenetic analysis, A. marginale based on 16 rDNA clustered with A. marginale, while gltA and ompB sequences clustered with R. raoultii. This is the first study on the genetic characterization of D. marginatus and associated A. marginale and R. raoultii in Pakistan. The northern areas of Pakistan, which need to be explored in terms of ticks and associated pathogens due to their zoonotic threats, have been neglected due to the inaccessible climatic conditions. [ABSTRACT FROM AUTHOR]

Anaplasma marginale (A. marginale), Anaplasma ovis (A. ovis) and Theileria ovis (T. ovis) are among the most commonly reported intracellular tick borne pathogens that infect ruminants across the globe causing huge economic losses. This study aims to report the prevalence and phylogenetic evaluation of these three pathogens infecting sheep and goats (n = 333) that were enrolled from Fort Munro region in Pakistan by using msp1b, msp4 and 18S rRNA genes for A. marginale, A. ovis and T. ovis respectively. Results revealed almost similar infection rates in sheep and goats with an overall prevalence of 11% for A. marginale, 28% for A. ovis and 3% for T. ovis. Concurrent infection was also recorded, however, the number of animals infected with two pathogens (n = 24; 7.2%) was higher than infection with three pathogens (n = 2; 0.6%). Risk factor analysis revealed that sheep reared in small herds had higher A. marginale (P = 0.03) and A. ovis (P = 0.04) infection rates compared to those from large herds. In addition, it was observed that bucks (P ≤ 0.05) and tick-free goats (P ≤ 0.05) exhibited higher A. ovis infection rates than nannies. Phylogenetic analysis of all three pathogens showed that Pakistani isolates were clustered together and were closely related to previously deposited Pakistani isolates as well as with those that were reported from worldwide countries. In conclusion, we are reporting that Pakistani sheep and goats have A. marginale, A. ovis and T. ovis mediated infections and control measures should be taken against them to improve the productivity of the livestock sector. [ABSTRACT FROM AUTHOR]

Sarcoptes scabiei is an ectoparasite of humans and animals that causes scabies. The Rhipicephalus (Boophilus) microplus is a blood-sucking ectoparasite that transmits various pathogens. These two parasites have caused great losses to a country's dairy and agriculture sectors. The aim of this study was to determine the in vitro and in silico efficacy of Camellia sinensis plant extracts. Different concentrations of C. sinensis ethanolic plant extracts were prepared using the maceration method and were used against mites and ticks (in adult immersion test AIT and larval packet test LPT) to evaluate their in vitro acaricidal activity. Additionally, in silico molecular docking was performed to investigate the inhibitory interactions between the phytochemicals of the plant and S. scabiei and R. microplus glutathione transferase proteins (SsGST and RmGST). This study observed that the plant extract showed high efficacy in vitro against mites and different tick stages in adult immersion and larval packet tests. Additionally, the in silico study revealed a strong binding interaction between ellagic acid and SsGST protein, with a binding energy of −7.3 kcal/mol, with respect to permethrin (−6.7 kcal/mol), whereas quercetin and RmGST resulted in a docking score of −8.6 kcal/mol compared to deltamethrin (−8.2 kcal/mol). Overall, this study explored the potential of C. sinensis as a natural alternative for controlling tick and mite infestations and provided insights into the inhibitory mechanisms of its phytochemicals. [ABSTRACT FROM AUTHOR]

Caprine theileriosis, caused by Theileria ovis is a serious production issue, especially in the areas that depend on goats and sheep for milk, meat, and other economic benefits. Pakistan has a large goat population, but few reports have been documented from this country regarding PCR-based detection of T. ovis. The molecular prevalence of T. ovis, on a seasonal basis, in various goat breeds enrolled from Muzaffar Garh district of Punjab in Pakistan was determined from October 2018 to September 2019. In this study, 1084 goat blood samples were screened for the detection of T. ovis DNA through PCR-based amplification of 18S rRNA gene. Out of 1084 goats, 12 (1.11%) were infected with T. ovis. The parasite prevalence varied with the sampling seasons (Chi square test, P = 0.008), and the parasite prevalence was highest in goat blood samples collected in summer (2.39%) followed by winter (1.88%). DNA sequencing and BLAST analysis confirmed the presence of T. ovis, and the amplified isolates from the 18S rRNA gene of T. ovis were found to be highly conserved during phylogenetic analysis. Young goats (Fischer exact test, P = 0.022) were found more infected with T. ovis during the winter season. Infected goats had elevated white blood cell counts (Two-sample t-test, P = 0.04), blood urea nitrogen to Creatinine ratio (Two-sample t-test, P = 0.02) and decreased serum Creatinine (Two-sample t-test, P = 0.001) as compared to T. ovis negative goats. We report a relatively low molecular prevalence of T. ovis in goats from the Muzaffar Garh district. However, it is recommended that control measures to eradicate T. ovis infection in goats in this area should be taken. [ABSTRACT FROM AUTHOR]

Theileria annulata (T. annulata) and Anaplasma marginale (A. marginale) are among the most extensively reported tick borne pathogens and are associated with huge economic losses worldwide. A total of 298 cattle blood samples were screened to report the presence of these two pathogens. The samples were collected from apparently healthy cattle (Achai, n = 155, Jersy, n = 88 and crossbred, n = 55) in Bajaur district of Khyber Pakhtunkhwa (KPK) during June and July of 2022. A total of 31 out of 298 cattle (10.4%) were found infected with T. annulata as PCR amplified a 156 base pair fragment from Tams-1 gene of T. annulata from their blood. While 16/298 animals (5.4%) were found infected with A. marginale as they amplified a 382 base pair fragment specific for msp5 gene of this bacterium. Three animals (1%) were found co infected. Cattle susceptibility to T. annulata infection was significantly higher than A. marginale infection (P < 0.001). Phylogenetic analysis revealed that Pakistani isolates of both detected pathogen clustered together and were closely related isolates from worldwide countries. Prevalence of T. annulata varied significantly among the sampling sites (P = 0.05) while no such association was observed for A. marginale among the tested cattle. Epidemiological data analysis revealed that none of the studied risk factors was found associated either with the prevalence of T. annulata or A. marginale (P > 0.05) among enrolled cattle. In conclusion, our study has revealed a relatively higher prevalence of T. annulata than A. marginale in cattle from the Bajaur district in KPK. This information is important for improving the productivity of the livestock sector, which is one of the main sources of income in the country. It is recommended that this data be taken into account for the development and implementation of effective tick control programs, as well as for the improvement of livestock management practices to prevent and manage TBDs in Pakistan. [ABSTRACT FROM AUTHOR]

Discovering the interactions between the persons mentioned in a set of topic documents can help readers construct the background of the topic and facilitate document comprehension. To discover person interactions, we need a detection method that can identify text segments containing information about the interactions. Information extraction algorithms then analyze the segments to extract interaction tuples and construct a network of person interaction. In this article, we define interaction detection as a classification problem. The proposed interaction detection method, called feature-based interactive segment recognizer (FISER), exploits 19 features covering syntactic, context-dependent, and semantic information in text to detect intra-clausal and inter-clausal interactive segments in topic documents. Empirical evaluations demonstrate that FISER outperformed many well-known relation extraction and protein-protein interaction detection methods on identifying interactive segments in topic documents. In addition, the precision, recall, and F1-score of the best feature combination are 72.9%, 55.8%, and 63.2%, respectively. [ABSTRACT FROM AUTHOR]

Ticks and tick-borne diseases constitute a substantial hazard to the livestock industry. The rising costs and lack of availability of synthetic chemical acaricides for farmers with limited resources, tick resistance to current acaricides, and residual issues in meat and milk consumed by humans further aggravate the situation. Developing innovative, eco-friendly tick management techniques, such as natural products and commodities, is vital. Similarly, searching for effective and feasible treatments for tick-borne diseases is essential. Flavonoids are a class of natural chemicals with multiple bioactivities, including the inhibition of enzymes. We selected eighty flavonoids having enzyme inhibitory, insecticide, and pesticide properties. Flavonoids' inhibitory effects on the acetylcholinesterase (AChE1) and triose-phosphate isomerase (TIM) proteins of Rhipicephalus microplus were examined utilizing a molecular docking approach. Our research demonstrated that flavonoids interact with the active areas of proteins. Seven flavonoids (methylenebisphloridzin, thearubigin, fortunellin, quercetagetin-7-O-(6-O-caffeoyl-β-d-glucopyranoside), quercetagetin-7-O-(6-O-p-coumaroyl-β-glucopyranoside), rutin, and kaempferol 3-neohesperidoside) were the most potent AChE1 inhibitors, while the other three flavonoids (quercetagetin-7-O-(6-O-caffeoyl-β-d-glucopyranoside), isorhamnetin, and liquiritin) were the potent inhibitors of TIM. These computationally-driven discoveries are beneficial and can be utilized in assessing drug bioavailability in both in vitro and in vivo settings. This knowledge can create new strategies for managing ticks and tick-borne diseases. [ABSTRACT FROM AUTHOR]

Viola canescens Wall. is an important medicinal plant with reported therapeutic benefits. The current work sought to investigate the antidiarrheal properties of V. canescens extracts both in vivo and in silico. This study applied molecular docking to unravel the molecular mechanism of V. canescens and to find the most effective phytocompounds with antidiarrheal effects. The antidiarrheal activity of V. canescens was assessed utilizing the castor oil-induced diarrhea assay and the charcoal meal assay. Antidiarrheal characteristics were evaluated by measuring parameters such as intestinal motility, fecal score, and hypersecretion. The V. canescens extract had a dose-dependent and statistically significant impact in the charcoal meal assay and castor oil-induced diarrhea assay. In the castor oil-induced diarrhea assay, the ethyl acetate fraction (65.96%) showed the highest percentage of defecation inhibition at the highest dose (300 mg/kg (bw)), followed by the uncorrected crystalline compound (63.83%), crude alkaloids (63.83%), chloroform fraction (63.83%), and crude flavonoids (55.32%), while the aqueous fraction (40.43%) and n-Hexane fraction (42.55%) revealed the lowest antidiarrheal potential. In addition, the molecular docking investigation showed emetine, quercetin, and violanthin, isolated chemicals of V. canescens, to have the highest binding affinity to the target μ and δ opioid receptors with significant inhibitory capacity. These pharmacologically active metabolites in V. canescens were effective in treating diarrhea. This study lends credence to the traditional usage of V. canescens in treating gastrointestinal disorders. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) infection can induce life-threatening dengue hemorrhagic fever/dengue shock syndrome in infected patients. DENV is a threat to global health due to its growing numbers and incidence of infection in the last 50 years. During infection, DENV expresses ten structural and nonstructural proteins modulating cell responses to benefit viral replication. However, the lack of knowledge regarding the cellular proteins and their functions in enhancing DENV pathogenesis impedes the development of antiviral drugs and therapies against fatal DENV infection. Here, we identified that integrin-linked kinase (ILK) is a novel enhancing factor for DENV infection by suppressing type I interferon (IFN) responses. Mechanistically, ILK binds DENV NS1 and NS3, activates Akt and Erk, and induces NF-κB-driven suppressor of cytokine signaling 3 (SOCS3) expression. Elevated SOCS3 in DENV-infected cells inhibits phosphorylation of STAT1/2 and expression of interferon-stimulated genes (ISGs). Inhibiting ILK, Akt, or Erk activation abrogates SOCS3 expression. In DENV-infected mice, the treatment of an ILK inhibitor significantly reduces viral loads in the brains, disease severity, and mortality rate. Collectively, our results show that ILK is a potential therapeutic target against DENV infection. Author summary: Dengue virus (DENV) can alter cell responses to benefit viral replication. However, most cellular proteins, especially those enhancing viral replication, remains unknown, and their roles in DENV pathogenesis are elusive. Here, we show that integrin-linked kinase (ILK) enhanced DENV infection. ILK binds DENV NS1 and NS3 to induce SOCS3 expression and abrogate STAT1/2-mediated expression of interferon-stimulated genes via the Akt-Erk- NF-κB pathway. Knockdown or inhibiting ILK enhances SOCS3 expression and reduces DENV yields in cells. Furthermore, inhibiting ILK in DENV-infected mice significantly decreased viral loads in the mouse brain and mortality. In conclusion, we identified ILK as a potential therapeutic target for DENV infection. [ABSTRACT FROM AUTHOR]

A topic is defined as a seminal event or activity along with all directly related events and activities. It is represented by a chronological sequence of documents published by different authors on the Internet. In this study, we define a task called topic anatomy, which summarizes and associates the core parts of a topic temporally so that readers can understand the content easily. The proposed topic anatomy model, called TSCAN, derives the major themes of a topic from the eigenvectors of a temporal block association matrix. Then, the significant events of the themes and their summaries are extracted by examining the constitution of the eigenvectors. Finally, the extracted events are associated through their temporal closeness and context similarity to form an evolution graph of the topic. Experiments based on the official TDT4 corpus demonstrate that the generated temporal summaries present the storylines of topics in a comprehensible form. Moreover, in terms of content coverage, coherence, and consistency, the summaries are superior to those derived by existing summarization methods based on human-composed reference summaries. [ABSTRACT FROM AUTHOR]

Major cancer deaths can be ascribed to distant metastasis to which the assembly of pericellular fibronectin (periFN) on suspended tumor cells (STCs) in the bloodstream that facilitate endothelial attachment can lead. Even though mangosteen pericarps (MP) extracts and the major component α-mangostin (α-MG) exhibit potent cancer chemopreventive properties, whether they can prophylactically and therapeutically be used as dietary nutraceuticals to prevent distant metastasis by suppressing periFN assembly on STCs within the circulation remains obscure. Immunofluorescence staining, MTT assays, flow cytometric assays, immunoblotting, and experimental metastasis mouse models were used to detect the effects of MP extracts or α-MG on periFN on STCs, tumor cell proliferation and apoptosis, the AKT activity, and tumor lung metastasis. The periFN assembly on STCs was significantly diminished upon treatments of STCs with either α-MG or MP extracts in a dose-dependent manner without inhibiting cell proliferation and viability due to increased AKT activity. Pretreatment of STCs with α-MG appeared to suppress tumor lung metastasis and prolong mouse survival rates. Oral gavage with MP extracts could therapeutically, but not prophylactically, prevent lung metastasis of STCs. We concluded that MP extracts or the major component α-MG may therapeutically serve as a potent anti-metastatic nutraceutical. [ABSTRACT FROM AUTHOR]

Background: While magnetic resonance imaging (MRI) is the imaging modality of choice for the evaluation of patients with brain tumors, it may still be challenging to differentiate glioblastoma multiforme (GBM) from solitary brain metastasis (SBM) due to their similar imaging features. This study aimed to evaluate the features extracted of dual-tree complex wavelet transform (DTCWT) from routine MRI protocol for preoperative differentiation of glioblastoma (GBM) and solitary brain metastasis (SBM). Methods: A total of 51 patients were recruited, including 27 GBM and 24 SBM patients. Their contrast-enhanced T1-weighted images (CET1WIs), T2 fluid-attenuated inversion recovery (T2FLAIR) images, diffusion-weighted images (DWIs), and apparent diffusion coefficient (ADC) images were employed in this study. The statistical features of the pre-transformed images and the decomposed images of the wavelet transform and DTCWT were utilized to distinguish between GBM and SBM. Results: The support vector machine (SVM) showed that DTCWT images have a better accuracy (82.35%), sensitivity (77.78%), specificity (87.50%), and the area under the curve of the receiver operating characteristic curve (AUC) (89.20%) than the pre-transformed and conventional wavelet transform images. By incorporating DTCWT and pre-transformed images, the accuracy (86.27%), sensitivity (81.48%), specificity (91.67%), and AUC (93.06%) were further improved. Conclusions: Our studies suggest that the features extracted from the DTCWT images can potentially improve the differentiation between GBM and SBM. [ABSTRACT FROM AUTHOR]

Crassolide, a cembranoid diterpene extracted from the soft coral Lobophytum crissum, has been proven to possess antioxidant and immunomodulatory properties. In the present study, we assessed the anticancer effects of crassolide on human H460 non-small-cell lung cancer (NSCLC) cells. We found that crassolide exerted cytotoxic effects on H460 cancer cells in vitro, inducing G2/M phase arrest and apoptosis. In addition, in H460 cells exposed to crassolide, the expression of the autophagy-related proteins LC3-II and beclin was increased, while the expression of p62 was decreased. Moreover, inhibiting autophagy with chloroquine (CQ) suppressed the crassolide-induced G2/M arrest and apoptosis of H460 cells. Moreover, we also found that crassolide induced endoplasmic reticulum (ER) stress in lung cancer cells by increasing the expression of ER stress marker proteins and that the crassolide-induced G2/M arrest, apoptosis, and autophagy were markedly attenuated by the ER stress inhibitor 4-phenylbutyric acid (4-PBA). Furthermore, we found that crassolide promoted reactive oxygen species (ROS) production by H460 cells and that the ROS inhibitor N-acetylcysteine (NAC) decreased the crassolide-induced ER stress, G2/M arrest, apoptosis, and autophagy. In conclusion, our findings show that crassolide inhibits NSCLC cell malignant biological behaviors for the first time, suggesting that this effect may be mechanistically achieved by inducing G2/M arrest, apoptosis, and autophagy through ROS accumulation, which activates the ER stress pathway. As a result of our findings, we now have a better understanding of the molecular mechanism underlying the anticancer effect of crassolide, and we believe crassolide might be a candidate for targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Sclerosing microcystic adenocarcinoma is a rare and recently characterized cancer that affects the mucosal surfaces of the head and neck without adnexal involvement. Histologically, microcystic adnexal carcinoma of the skin resembles it. It does, however, contain unique characteristics that merit our attention for potential diagnostic errors. Therefore, we present a 48-year-old male with sclerosing microcystic adenocarcinoma of the tongue, along with a full discussion and a brief review of pertinent literature. [ABSTRACT FROM AUTHOR]

Ovarian teratomas are by far the most common ovarian germ cell tumor. Most teratomas are benign unless a somatic transformation occurs. The designation of teratoma refers to a neoplasm that differentiates toward somatic-type cell populations. Recent research shows a striking association between ovarian teratomas and anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, a rare and understudied paraneoplastic neurological syndrome (PNS). Among teratomas, mature teratomas are thought to have a greater relevance with those neurological impairments. PNS is described as a neurologic deficit triggered by an underlying remote tumor, whereas anti-NMDAR encephalitis is characterized by a complex neuropsychiatric syndrome and the presence of autoantibodies in cerebral spinal fluid against the GluN1 subunit of the NMDAR. This review aims to summarize recent reports on the association between anti-NMDAR encephalitis and ovarian teratoma. In particular, the molecular pathway of pathogenesis and the updated mechanism and disease models would be discussed. We hope to provide an in-depth review of this issue and, therefore, to better understand its epidemiology, diagnostic approach, and treatment strategies. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid (LPA) is a bioactive lipid mediator primarily derived from membrane phospholipids. LPA initiates cellular effects upon binding to a family of G protein-coupled receptors, termed LPA receptors (LPAR1 to LPAR6). LPA signaling drives cell migration and proliferation, cytokine production, thrombosis, fibrosis, angiogenesis, and lymphangiogenesis. Since the expression and function of LPA receptors are critical for cellular effects, selective antagonists may represent a potential treatment for a broad range of illnesses, such as cardiovascular diseases, idiopathic pulmonary fibrosis, voiding dysfunctions, and various types of cancers. More new LPA receptor antagonists have shown their therapeutic potentials, although most are still in the preclinical trial stage. This review provided integrative information and summarized preclinical findings and recent clinical trials of different LPA receptor antagonists in cancer progression and resistance. Targeting LPA receptors can have potential applications in clinical patients with various diseases, including cancer. [ABSTRACT FROM AUTHOR]

AbstractEconomy of Pakistan is heavily dependent upon agriculture and extensive use of pesticide is quiet common to enhance the crop yield. Imidacloprid is among the first choice pesticides in Pakistan and it has been reported that through run off along with water it ends up in water bodies affecting non target aquatic fauna. Through the present investigation, we are reporting the effects of Imidacloprid on the fatty acids composition of a non-target, commercially important carp: Labeo rohita. Fish were exposed to sub lethal concentration of Imidacloprid (120 mgL1) for 2, 4 and 8 days (short term) as well as for 16, 32 and 64 days (long term experimental conditions). Pesticide untreated controls were also maintained for each treatment. Following the specific Imidacloprid exposure, fatty acid composition (%) was determined in the muscle of all experimental groups by using gas chromatography. Fish exposed to Imidacloprid for 8 days had reduced Palmitic acid (p = 0.02) and elevated muscle Arachidic acid (p < 0.001) than control group. Labeo rohita exposed to the pesticide for 32 days had elevated muscle Oleic (p = 0.02) and Linoleic acid (p = 0.02) while fish exposed to Imidacloprid to 64 days had reduced muscle Palmitic (p = 0.04) and Oleic acid (p = 0.03). In conclusion, we are reporting that the exposure to sub lethal concentration of Imidacloprid disturb the muscle fatty acid composition of Labeo rohita that may affect its food quality. The effects were more pronounced under long term experimental conditions and were probably due to potentiating lipid peroxidation and disturbed fish metabolism upon Imidacloprid exposure. [ABSTRACT FROM AUTHOR]

In many human cancers, including hepatocellular carcinoma (HCC), high density of infiltrating tumor-associated macrophages (TAM) is associated with poor prognosis. Most TAMs express a M2 phenotype subsequently supporting tumor growth. How tumor cells polarize these TAMs to a pro-tumor M2 phenotype is still poorly understood. Our previous studies have revealed that a Toll-like receptor 2 (TLR2)-dependent autophagy triggered by hepatoma-derived factors down-regulates NF-κB p65 and drives M2 macrophage differentiation. However, the underlying mechanisms and potential hepatoma-derived TLR2 ligands are not clear. Here, we provide evidence to reveal that NADPH oxidase 2 (NOX2)-dependent reactive oxygen species (ROS) generation is crucial for HCC-induced autophagy, NF-κB p65 down-regulation and M2 phenotype polarization in primary macrophages. This NOX2-generated ROS production in abolished in TLR2-deficient macrophages. HCC-derived or recombinant high-mobility group box 1 (HMGB1) is able to trigger this TLR2-mediated M2 macrophage polarization. Blockage of HMGB1 and ROS by inhibitors, ethyl pyruvate and N-acetylcysteine amide, respectively, significantly reduces both M2 macrophage accumulation and liver nodule formation in HCC-bearing mice. Our findings uncover a HMGB1/TLR2/NOX2/autophagy axis to trigger M2 macrophage polarization in HCC that can be considered as a novel therapeutic target for treating HCC. [ABSTRACT FROM AUTHOR]

Objective. Human colorectal cancer (CRC) is the third most common cancer; patients with metastatic colorectal cancer (mCRC) show poor prognosis than those with CRC cases. There are no reliable molecular biomarkers for the diagnosis of CRC prognosis except with pathological features. Therefore, it is urgent to develop a biomarker for diagnosis and/or prediction of human CRC. In addition, capping actin protein (CapG) belongs to the gelsolin family and has been reported to contribute on tumor invasion/metastasis in multiple human cancers. Here, we are the first to evaluate the expression of CapG in human CRCs. Study Design. To investigate the expression levels of CapG in human tissue array by immunohistochemistry (IHC) staining. Moreover, the mRNA and protein levels were also confirmed in four CRC cell lines and determined using real-time RT-PCR and Western blotting. Finally, a Matrigel transwell invasion assay was used to evaluate the invasion ability in CapG high or low expression cells. Results. We demonstrated that CapG could be determined in the normal colon tissue and human CRC specimens. However, CapG was significantly overexpressed in the mCRC specimens compared with that in CRC specimens and normal cases. It was also detectable in the four CRC cell lines including mRNA and protein levels. We also found that knockdown of the expression of CapG reduced tumor migration. Conclusions. In this study, we suggested that CapG could be used as a biomarker for metastatic CRC in the clinical specimens. Moreover, our in vitro study demonstrated that CapG might contribute on tumor metastasis in human CRCs. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common cancers in Taiwan. Although chemotherapy is the primary treatment for HCC patients, drug resistance often leads to clinical failure. Galectin-1 is a beta-galactoside binding lectin which is up-regulated in HCC patients and promotes tumor growth by mediating cancer cell adhesion, migration and proliferation, but its role in chemoresistance of HCC is poorly understood. In this study we found that galectin-1 is able to lead to chemoresistance against cisplatin treatment, and subsequent inhibition has reversed the effect of cell death in HCC cells. Moreover, galectin-1 was found to induce autophagic flux in HCC cells. Inhibition of autophagy by inhibitors or knockdown of Atg5 cancels galectin-1-induced cisplatin resistance in HCC cells. Increase of mitophagy triggered by galectin-1 was found to reduce the mitochondrial potential loss and apoptosis induced by cisplatin treatment. Finally, using an in situ hepatoma mouse model, we clearly demonstrated that inhibition of galectin-1 by thiodigalactoside could significantly augment the anti-HCC effect of cisplatin. Taken together, our findings offer a new insight into the chemoresistance galectin-1 causes against cisplatin treatment, and points to a potential approach to improve the efficacy of cisplatin in the treatment of HCC patients. [ABSTRACT FROM AUTHOR]

Prostate cancer is featured by its heterogeneous nature, which indicates a different prognosis. Castration-resistant prostate cancer (CRPC) is a hallmark of the treatment-refractory stage, and the median survival of patients is only within two years. Neuroendocrine prostate cancer (NEPC) is an aggressive variant that arises from de novo presentation of small cell carcinoma or treatment-related transformation with a median survival of 1–2 years from the time of diagnosis. The epigenetic regulators, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been proven involved in multiple pathologic mechanisms of CRPC and NEPC. LncRNAs can act as competing endogenous RNAs to sponge miRNAs that would inhibit the expression of their targets. After that, miRNAs interact with the 3' untranslated region (UTR) of target mRNAs to repress the step of translation. These interactions may modulate gene expression and influence cancer development and progression. Otherwise, epigenetic regulators and genetic mutation also promote neuroendocrine differentiation and cancer stem-like cell formation. This step may induce neuroendocrine prostate cancer development. This review aims to provide an integrated, synthesized overview under current evidence to elucidate the crosstalk of lncRNAs with miRNAs and their influence on castration resistance or neuroendocrine differentiation of prostate cancer. Notably, we also discuss the mechanisms of lncRNA–miRNA interaction in androgen receptor-independent prostate cancer, such as growth factors, oncogenic signaling pathways, cell cycle dysregulation, and cytokines or other transmembrane proteins. Conclusively, we underscore the potential of these communications as potential therapeutic targets in the future. [ABSTRACT FROM AUTHOR]

Appendicitis is a common surgical abdominal disease with various presentations. Its diagnosis may be obscured by asymptomatic congenital anatomical anomalies like midgut malrotation. Midgut malrotation is a rare fetal anomaly resulting from incomplete or failure of midgut rotation and fixation. It is mostly presented with bowel obstruction or volvulus in early life. Presentation in adult is rare. Here, we report an elderly patient presented with left lower abdominal pain and urinary tract infection. Abdominal computed tomography revealed left-sided appendicitis with non-rotational-type midgut malrotation. Clinicians should bear in mind the possibility of underlying midgut malrotation, as appendicitis could be the first presentation of this rare congenital condition. [ABSTRACT FROM AUTHOR]

The presence of adipocytes within thyroid glands is a rare finding seen in thyrolipoma, diffuse lipomatosis, or thyroid teratoma. Although some cases present with multinodular goiter or autoimmune thyroiditis, the exact cause has not yet been elucidated. Among reported cases, thyrolipomas mainly occur in females and usually present as a solitary lesion. However, a few reported cases had coexisting papillary thyroid carcinomas. Herein, we present a 51-year-old female with synchronous thyrolipoma (2.0 × 1.5 × 1.3 cm) and papillary thyroid carcinoma (0.7 × 0.6 × 0.6 cm) within the same thyroid lobe. She had diabetes mellitus and hypertension and complained of anterior neck enlargement and discomfort for three months. Thyroid sonography showed multiple hypoechoic nodules, one of which was heterogeneous and ill-defined. Fine needle aspirate cytology for the ill-defined nodule was suspicious for papillary thyroid carcinoma. She subsequently received radical thyroidectomy and neck lymph node dissection. Histopathologically, one thyrolipoma and one papillary thyroid carcinoma were identified in the right lobe of the thyroid gland without metastases of lymph nodes, while other nodules were multinodular goiter. Notably, thyrolipoma may not be simply an incidental finding but might coexist with thyroid carcinomas. A brief review of the pertinent literature of prior reports is also provided. [ABSTRACT FROM AUTHOR]

Decellularized vascular grafts are useful for the construction of biological small-diameter tissue-engineered vascular grafts (≤6 mm). Traditional chemical decellularization requires a long treatment time, which may damage the structure and alter the mechanical properties. Decellularization using sonication is expected to solve this problem. The aim of this study was to develop an effective decellularization method using ultrasound followed by washing. Different power values of sonication at 40 kHz were tested for 2, 4, and 8 h followed by a washing procedure. The efficacy of sonication of decellularized human umbilical artery (sDHUA) was evaluated via DNA content, histological staining, mechanical properties, and biocompatibility. The sDHUAs were further implanted into rats for up to 90 days and magnetic resonance angiography (MRA) was performed for the implanted grafts. The results demonstrated that treatment of human umbilical artery (HUA) by sonication at ultrasonic power of 204 W for 4 h followed by washing for 24 h in 2% SDS buffer could eliminate more than 90% of cells and retain similar mechanical properties of the HUA. Recellularization was assessed by scanning electron microscopy (SEM), which indicated that sDHUA provided niches for human umbilical vein endothelial cells (HUVECs) to reside, indicating in vitro cytocompatibility. Further implantation tests also indicated the fitness of the sonication-treated HUA as a scaffold for small-caliber tissue engineering vascular grafts. [ABSTRACT FROM AUTHOR]

Background: Purely cutaneous Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder limited to the skin. To date, its pathogenesis remains unclear. Owing to recent findings of specific mutations in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in histiocytic proliferative disorders, it provides a novel perspective on the pathomechanism of cutaneous RDD. We aim to investigate the genomic mutations in MAPK/ERK pathway in cutaneous RDD. Methods: We retrospectively recruited all cases of cutaneous RDD from two hospitals in Taiwan from January 2010 to March 2020 with the clinicopathologic features, immunohistochemistry, and treatment. Mutations of neuroblastoma RAS viral oncogene homolog (NRAS), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in MAPK/ERK pathway were investigated by the highly sensitive polymerase chain reaction with Sanger sequencing. Results: Seven patients with cutaneous RDD were recruited with nine biopsy specimens. The median age was 46 years (range: 17–62 years). Four of seven patients (57.1%) received tumor excision, while the other three chose oral and/or topical or intralesional steroids. NRAS mutation was detected in 4 of 7 cases (4/7; 51.7%), and NRAS A146T was the most common mutant point (n = 4/7), followed by NRAS G13S (n = 2/7). There is no KRAS or BRAF mutation detected. Conclusions: We report the NRAS mutation is common in cutaneous RDD, and NRAS A146T was the most frequent mutation in this cohort. Mutations in the NRAS gene can activate the RAS/MAPK signaling and have been reported to be associated with various cancers. It indicates that NRAS mutation in MAPK/ERK pathway may involve the pathogenesis of cutaneous RDD. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) infection is a significant public health threat in tropical and subtropical regions; however, there is no specific antiviral drug. Accumulated studies have revealed that DENV infection induces several cellular responses, including autophagy and apoptosis. The crosstalk between autophagy and apoptosis is associated with the interactions among components of these two pathways, such as apoptotic caspase-mediated cleavage of autophagy-related proteins. Here, we show that DENV-induced autophagy inhibits early cell apoptosis and hence enhances DENV replication. Later, the apoptotic activities are elevated to suppress autophagy through cleavage of Beclin-1, an essential autophagy-related protein. Inhibition of cleavage of Beclin-1 by a pan-caspase inhibitor, Z-VAD, increases both autophagy and viral replication. Regarding the mechanism, we further found that DENV nonstructural protein 1 (NS1) is able to interact with Beclin-1 during DENV infection. The interaction between Beclin-1 and NS1 attenuates Beclin-1 cleavage and facilitates autophagy to prevent cell apoptosis. Our study suggests a novel mechanism whereby NS1 preserves Beclin-1 for maintaining autophagy to antagonize early cell apoptosis; however, elevated caspases trigger apoptosis by degrading Beclin-1 in the late stage of infection. These findings suggest implications for anti-DENV drug design. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid carcinoma (ATC) is rare but highly aggressive. We investigated the association of selected driver mutations, including BRAF, RAS,PIK3CA, TERT promoter, TP53, POLE, and mismatch repair deficiency (MMR-D) with the clinicopathological features of ATC to identify prognostic and predictive biomarkers. Thirty-nine retrospective cases from pathology archives were enrolled for clinicopathology analysis and immunohistochemistry, and 27 cases had sufficient specimens for further molecular testing using targeted next-generation sequencing and mass spectrometry. BRAFV600E and RAS mutations were identified in 25.9% and 40.7% of ATC, respectively. BRAFV600E mutation was significantly associated with coexisting papillary thyroid carcinoma (p = 0.009) and RAS mutations with female gender (p = 0.012). In univariant analysis, the non-BRAF/RAS tumors were significantly associated with the presence of a sarcomatoid pattern (p = 0.045). PIK3CA, TERT promoter, and TP53 mutations were identified in 14.8%, 81.5%, and 70.4% of cases, respectively. No MMR-D or POLE mutations were detected. In survival analyses, RAS and PIK3CA mutations were significantly associated with inferior outcomes (p = 0.03 and p = 0.006, respectively). In conclusion, driver mutations in ATC are associated with distinct clinicopathological features. RAS and PIK3CA mutations were negative predictors for patient survival. Emerging therapeutic agents targeting BRAF, RAS, and PI3 kinase may benefit a substantial proportion of ATC patients. [ABSTRACT FROM AUTHOR]

Cellular angiofibroma is a rare benign mesenchymal neoplasm most commonly occurring in the vulvovaginal region in women and the inguinoscrotal region in men with specific genetic deletion involved in the RB1 gene in chromosome 13q14 region. Atypical cellular angiofibroma and cellular angiofibroma with sarcomatous transformation are recently described variants showing worrisome morphological features and strong, diffuse p16 expression. Nevertheless, the molecular profile of these tumor entities is largely unknown. We carried out a next generation sequencing (NGS) study from six cases of atypical cellular angiofibroma and cellular angiofibroma with sarcomatous transformation. We were able to identify oncogenic TP53 gene mutations (33%) which may contribute to pathogenesis also resulting in p16 overexpression. In addition, RB1 gene alterations generally present were identified. Since it is a recently described and rare entity, the whole molecular signaling pathway is still largely obscured and the analysis of larger cohorts is needed to elucidate this issue. [ABSTRACT FROM AUTHOR]

Hutchinson–Gilford progeria syndrome (HGPS) is a rare laminopathy that produces a mutant form of prelamin A, known as Progerin, resulting in premature aging. HGPS cells show morphological abnormalities of the nuclear membrane, reduced cell proliferation rates, accumulation of reactive oxygen species (ROS), and expression of senescence markers. Lysophosphatidic acid (LPA) is a growth factor‐like lipid mediator that regulates various physiological functions via activating multiple LPA G protein‐coupled receptors. Here, we study the roles of LPA and LPA receptors in premature aging. We report that the protein level of LPA3 was highly downregulated through internalization and the lysosomal degradation pathway in Progerin‐transfected HEK293 cells. By treating Progerin HEK293 cells with an LPA3 agonist (OMPT, 1‐Oleoyl‐2‐O‐methyl‐rac‐glycerophosphothionate) and performing shRNA knockdown of the Lpa3r transcript in these cells, we showed that LPA3 activation increased expression levels of antioxidant enzymes, consequently inhibiting ROS accumulation and ameliorating cell senescence. LPA3 was shown to be downregulated in HGPS patient fibroblasts through the lysosomal pathway, and it was shown to be crucial for ameliorating ROS accumulation and cell senescence in fibroblasts. Moreover, in a zebrafish model, LPA3 deficiency was sufficient to cause premature aging phenotypes in multiple organs, as well as a shorter lifespan. Taken together, these findings identify the decline of LPA3 as a key contributor to the premature aging phenotypes of HGPS cells and zebrafish. [ABSTRACT FROM AUTHOR]

Background: S1P has been shown to improve the endothelialization of decellularized vascular grafts in vitro. Here, we evaluated the potential of tissue-engineered vascular grafts (TEVGs) constructed by ECs and S1P on decellularized vascular scaffolds in a rat model. Methods: Rat aorta was decellularized mainly by 0.1% SDS and characterized by histology. Rat ECs, were seeded onto decellularized scaffolds, and the viability of the ECs was evaluated by biochemical assays. Then, we investigated the in vivo patency rate and endothelialization for five groups of decellularized vascular grafts (each n = 6) in a rat abdominal aorta model for 14 days. The five groups included (1) rat allogenic aorta (RAA); (2) decellularized RAA (DRAA); (3) DRAA with S1P (DRAA/S1P); (4) DRAA with EC recellularization (DRAA/EC); and (5) DRAA with S1P and EC recellularization (DRAA/EC/S1P). Results: In vitro, ECs were identified by the uptake of Dil-Ac-LDL. S1P enhanced the expression of syndecan-1 on ECs and supported the proliferation of ECs on decellularized vascular grafts. In vivo, RAA and DRAA/EC/S1P both had 100% patency without thrombus formation within 14 days. Better endothelialization, more wall structure maintenance and less inflammation were noted in the DRAA/EC/S1P group. In contrast, there was thrombus formation in the DRAA, DRAA/S1P and DRAA/EC groups. Conclusion: S1P could inhibit thrombus formation to improve the patency rate of EC-covered decellularized vascular grafts in vivo and may play an important role in the construction of TEVGs. [ABSTRACT FROM AUTHOR]

Background: Renal hyperparathyroidism is a common complication of chronic kidney disease (CKD) or end-stage renal disease (ESRD) characterized by elevated parathyroid hormone levels secondary to derangements in the homeostasis of calcium, phosphate, and vitamin D. Rapid correction of severe and prolonged hyperparathyroidism by surgical parathyroidectomy in long-term hemodialysis patients occasionally causes hungry bone syndrome. These patients then exhibit severe and long-lasting secondary or tertiary hyperparathyroidism with high bone turnover. Case presentation: We report a case of recurrent tertiary hyperparathyroidism after total parathyroidectomy due to supernumerary parathyroid gland in a patient with long-term hemodialysis. Supplementation with intravenous calcium, oral calcium, and vitamin D immediately after patient surgery helps to prevent and treat hungry bone syndrome. Conclusions: We should prompt a search for the supernumerary parathyroid glands in ESRD patients, who have recurrent or persistent hyperparathyroidism after total parathyroidectomy. ESRD patients are more likely to develop hungry bone syndrome after parathyroidectomy. Prevention and treatment of hungry bone syndrome may be required after ectopic parathyroidectomy in clinical practice. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most common noncutaneous cancer in men worldwide. One of its major treatments is androgen deprivation therapy, but PCa frequently relapses as aggressive castration resistant local tumors and distal metastases. Hence, the development of novel agents or treatment modalities for advanced PCa is crucial. Many tumors, including PCa, first metastasize to regional lymph nodes via lymphatic vessels. Recent findings demonstrate that the bioactive lipid lysophosphatidic acid (LPA) promotes PCa progression by regulating vascular endothelial growth factor-C (VEGF-C), a critical mediator of tumor lymphangiogenesis and lymphatic metastasis. Many of the underlying molecular mechanisms of the LPA–VEGF-C axis have been described, revealing potential biomarkers and therapeutic targets that may aid in the diagnosis and treatment of advanced PCa. Herein, we review the literature that illustrates a functional role for LPA signaling in PCa progression. These discoveries may be especially applicable to anti-lymphangiogenic strategies for the prevention and therapy of metastatic PCa. [ABSTRACT FROM AUTHOR]