Enhancing the Spermidine Synthase-Based Polyamine Biosynthetic Pathway to Boost Rapid Growth in Marine Diatom Phaeodactylum tricornutum.

Diatoms, efficient carbon capture organisms, contribute to 20% of global carbon fixation and 40% of ocean primary productivity, garnering significant attention to their growth. Despite their significance, the synthesis mechanism of polyamines (PAs), especially spermidine (Spd), which are crucial for growth in various organisms, remains unexplored in diatoms. This study reveals the vital role of Spd, synthesized through the spermidine synthase (SDS)-based pathway, in the growth of the diatom Phaeodactylum tricornutum. PtSDS1 and PtSDS2 in the P. tricornutum genome were confirmed as SDS enzymes through enzyme-substrate selectivity assays. Their distinct activities are governed primarily by the Y79 active site. Overexpression of a singular gene revealed that PtSDS1, PtSDS2, and PtSAMDC from the SDS-based synthesis pathway are all situated in the cytoplasm, with no significant impact on PA content or diatom growth. Co-overexpression of PtSDS1 and PtSAMDC proved essential for elevating Spd levels, indicating multifactorial regulation. Elevated Spd content promotes diatom growth, providing a foundation for exploring PA functions and regulation in diatoms.

An Overview of the Potential of Food-Based Carbon Dots for Biomedical Applications.

Food-based carbon dots (CDs) hold significant importance across various fields, ranging from biomedical applications to environmental and food industries. These CDs offer unique advantages over traditional carbon nanomaterials, including affordability, biodegradability, ease of operation, and multiple bioactivities. This work aims to provide a comprehensive overview of recent developments in food-based CDs, focusing on their characteristics, properties, therapeutic applications in biomedicine, and safety assessment methods. The review highlights the potential of food-based CDs in biomedical applications, including antibacterial, antifungal, antivirus, anticancer, and anti-immune hyperactivity. Furthermore, current strategies employed for evaluating the safety of food-based CDs have also been reported. In conclusion, this review offers valuable insights into their potential across diverse sectors and underscores the significance of safety assessment measures to facilitate their continued advancement and application.

The Rapid Detection of Salmonella enterica, Listeria monocytogenes, and Staphylococcus aureus via Polymerase Chain Reaction Combined with Magnetic Beads and Capillary Electrophoresis.

Food safety concerns regarding foodborne pathogen contamination have gained global attention due to its significant implications. In this study, we developed a detection system utilizing a PCR array combined with an automated magnetic bead-based system and CE technology to enable the detection of three foodborne pathogens, namely Salmonella enterica, Listeria monocytogenes, and Staphylococcus aureus. The results showed that our developed method could detect these pathogens at concentrations as low as 7.3 × 101, 6.7 × 102, and 6.9 × 102 cfu/mL, respectively, in the broth samples. In chicken samples, the limit of detection for these pathogens was 3.1 × 104, 3.5 × 103, and 3.9 × 102 cfu/g, respectively. The detection of these pathogens was accomplished without the necessity for sample enrichment, and the entire protocols, from sample preparation to amplicon analysis, were completed in approximately 3.5 h. Regarding the impact of the extraction method on detection capability, our study observed that an automated DNA extraction system based on the magnetic bead method demonstrated a 10-fold improvement or, at the very least, yielded similar results compared to the column-based method. These findings demonstrated that our developed model is effective in detecting low levels of these pathogens in the samples analyzed in this study. The PCR-CE method developed in this study may help monitor food safety in the future. It may also be extended to identify other foodborne pathogens across a wide range of food samples.

Rapid detection methods for foodborne pathogens based on nucleic acid amplification: Recent advances, remaining challenges, and possible opportunities.

This article presents a review of recent advancements in the utilization of NAA-based techniques for detecting foodborne pathogens in food products, focusing on studies conducted within the past five years. This review revealed that recent research efforts have primarily aimed at enhancing sensitivity and specificity by improving sample pre-treatment/preparation, DNA isolation, and readout methods. Isothermal-based amplification methods, such as LAMP, RPA, RAA, and RCA, have emerged as promising approaches, providing rapid results within one h and often demonstrating comparable or superior sensitivity to conventional or qPCR methods. However, the attention paid to specific pathogens varies, with Salmonella spp., Listeria spp., E. coli, and V. parahaemolyticus receiving more focus than norovirus and other similar pathogens. NAA-based methods have the potential to significantly contribute to food safety and public health protection. However, further advancements are necessary to fully realize their benefits.

Integrins and Actions of Androgen in Breast Cancer.

Androgen has been shown to regulate male physiological activities and cancer proliferation. It is used to antagonize estrogen-induced proliferative effects in breast cancer cells. However, evidence indicates that androgen can stimulate cancer cell growth in estrogen receptor (ER)-positive and ER-negative breast cancer cells via different types of receptors and different mechanisms. Androgen-induced cancer growth and metastasis link with different types of integrins. Integrin αvß3 is predominantly expressed and activated in cancer cells and rapidly dividing endothelial cells. Programmed death-ligand 1 (PD-L1) also plays a vital role in cancer growth. The part of integrins in action with androgen in cancer cells is not fully mechanically understood. To clarify the interactions between androgen and integrin αvß3, we carried out molecular modeling to explain the potential interactions of androgen with integrin αvß3. The androgen-regulated mechanisms on PD-L1 and its effects were also addressed.

What is thyroid function in your just-diagnosed cancer patient?

The principal hormonal product of the thyroid gland, L-thyroxine (T4), is a prohormone for 3,3',5-triiodo-L-thyronine, T3, the major ligand of nuclear thyroid hormone receptors (TRs). At a cell surface thyroid hormone analogue receptor on cancer cell and endothelial cell plasma membrane integrin αvß3, however, T4 at physiological concentrations is biologically active and is the major ligand. At this site in solid tumor cells, T4 nongenomically initiates cell proliferation, is anti-apoptotic by multiple mechanisms, supports radioresistance and enhances cancer-related angiogenesis. In contrast, hypothyroidism has been reported clinically to slow tumor growth. At physiological levels, T3 is not biologically active at the integrin and maintenance of euthyroidism with T3 in cancer patients may be associated with slowed tumor proliferation. Against this background, we raise the possibility that host serum T4 levels that are spontaneously in the upper tertile or quartile of the normal range in cancer patients may be a factor that contributes to aggressive tumor behavior. Recent observations on tumor metastasis and tumor-associated propensity for thrombosis due to T4 also justify clinical statistical analysis for a relationship to upper tertile hormone levels. That reverse T3 (rT3) may stimulate tumor growth has recently been reported and thus the utility of adding this measurement to thyroid function testing in cancer patients requires assessment. In summary, T4 at physiological concentrations promotes tumor cell division and aggressiveness and euthyroid hypothyroxinemia arrests clinically advanced solid tumors. These findings support the clinical possibility that T4 levels in the upper tertile of the normal range require examination as a tumor supporting factor.

In Vitro and In Silico Biological Studies of 4-Phenyl-2-quinolone (4-PQ) Derivatives as Anticancer Agents.

Our previous study found that 2-phenyl-4-quinolone (2-PQ) derivatives are antimitotic agents, and we adopted the drug design concept of scaffold hopping to replace the 2-aromatic ring of 2-PQs with a 4-aromatic ring, representing 4-phenyl-2-quinolones (4-PQs). The 4-PQ compounds, whose structural backbones also mimic analogs of podophyllotoxin (PPT), maybe a new class of anticancer drugs with simplified PPT structures. In addition, 4-PQs are a new generation of anticancer lead compounds as apoptosis stimulators. On the other hand, previous studies showed that 4-arylcoumarin derivatives with 5-, 6-, and 7-methoxy substitutions displayed remarkable anticancer activities. Therefore, we further synthesized a series of 5-, 6-, and 7-methoxy-substituted 4-PQ derivatives (19-32) by Knorr quinoline cyclization, and examined their anticancer effectiveness. Among these 4-PQs, compound 22 demonstrated excellent antiproliferative activities against the COLO205 cell line (50% inhibitory concentration (IC50) = 0.32 µM) and H460 cell line (IC50 = 0.89 µM). Furthermore, we utilized molecular docking studies to explain the possible anticancer mechanisms of these 4-PQs by the docking mode in the colchicine-binding pocket of the tubulin receptor. Consequently, we selected the candidate compounds 19, 20, 21, 22, 25, 27, and 28 to predict their absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. Pharmacokinetics (PKs) indicated that these 4-PQs displayed good drug-likeness and bioavailability, and had no cardiotoxic side effects or carcinogenicity, but we detected risks of drug-drug interactions and AMES toxicity (mutagenic). However, structural modifications of these 4-PQs could improve their PK properties and reduce their side effects, and their promising anticancer activities attracted our attention for further studies.

Inhibition of White Spot Syndrome Virus (WSSV) in Pacific White Shrimp (Litopenaeus vannamei) Using Polyamine-Modified Carbon Quantum Dots.

White spot syndrome virus (WSSV), an enveloped double-stranded DNA virus, is the causative agent of white spot syndrome (WSS), which has been linked to cultured shrimp mass mortality in many countries. Therefore, the development of anti-WSSV agents is among the top priorities of the aquaculture sector. Here, we describe the preparation of polyamine-modified carbon quantum dots (polyamine CQDs) for the treatment of WSSV. Moreover, in vivo experiments were conducted in shrimp to confirm the anti-WSSV effect of the proposed CQD-based strategy.

Thyroid Hormone Induces Oral Cancer Growth via the PD-L1-Dependent Signaling Pathway.

Oral cancer is a fatal disease, and its incidence in Taiwan is increasing. Thyroid hormone as L-thyroxine (T4) stimulates cancer cell proliferation via a receptor on integrin αvß3 of plasma membranes. It also induces the expression of programmed death-ligand 1 (PD-L1) and cell proliferation in cancer cells. Thyroid hormone also activates ß-catenin-dependent cell proliferation in cancer cells. However, the relationship between PD-L1 and cancer proliferation is not fully understood. In the current study, we investigated the role of inducible thyroid hormone-induced PD-L1-regulated gene expression and proliferation in oral cancer cells. Thyroxine bound to integrin αvß3 to induce PD-L1 expressions via activation of ERK1/2 and signal transducer and activator of transcription 3 (STAT3). Inactivated STAT3 inhibited PD-L1 expression and nuclear PD-L1 accumulation. Inhibition of PD-L1 expression reduced ß-catenin accumulation. Furthermore, nuclear PD-L1 formed a complex with nuclear proteins such as p300. Suppression PD-L1 expression by shRNA blocked not only expression of PD-L1 and ß-catenin but also signal transduction, proliferative gene expressions, and cancer cell growth. In summary, thyroxine via integrin αvß3 activated ERK1/2 and STAT3 to stimulate the PD-L1-dependent and ß-catenin-related growth in oral cancer cells.

Extranuclear effects of thyroid hormones and analogs during development: An old mechanism with emerging roles.

Thyroid hormones, T3 (triiodothyronine) and T4 (thyroxine), induce a variety of long-term effects on important physiological functions, ranging from development and growth to metabolism regulation, by interacting with specific nuclear or cytosolic receptors. Extranuclear or nongenomic effects of thyroid hormones are mediated by plasma membrane or cytoplasmic receptors, mainly by αvß3 integrin, and are independent of protein synthesis. A wide variety of nongenomic effects have now been recognized to be elicited through the binding of thyroid hormones to this receptor, which is mainly involved in angiogenesis, as well as in cell cancer proliferation. Several signal transduction pathways are modulated by thyroid hormone binding to αvß3 integrin: protein kinase C, protein kinase A, Src, or mitogen-activated kinases. Thyroid hormone-activated nongenomic effects are also involved in the regulation of Na+-dependent transport systems, such as glucose uptake, Na+/K+-ATPase, Na+/H+ exchanger, and amino acid transport System A. Of note, the modulation of these transport systems is cell-type and developmental stage-dependent. In particular, dysregulation of Na+/K+-ATPase activity is involved in several pathological situations, from viral infection to cancer. Therefore, this transport system represents a promising pharmacological tool in these pathologies.

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-Glucoside improves female ovarian aging.

Reduced fertility associated with normal aging may reflect the over-maturity of oocytes. It is increasingly important to reduce aging-induced infertility since recent trends show people marrying at later ages. 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucoside (THSG), a polyphenol extracted from Polygonum multiflorum, has been reported to have anti-inflammatory and anti-aging properties. To evaluate whether THSG can reduce aging-related ovarian damage in a female mouse model of aging, THSG was administered by gavage at a dose of 10 mg/kg twice weekly, starting at 4 weeks of age in a group of young mice. In addition, the effect of THSG in a group of aged mice was also studied in mice starting at 24 weeks of age. The number of oocytes in the THSG-fed group was higher than in the untreated control group. Although the percentage of secondary polar bodies (PB2) decreased during aging in the THSG-fed group, it decreased much more slowly than in the age-matched control group. THSG administration increased the quality of ovaries in young mice becoming aged. Western blotting analyses also indicated that CYP19, PR-B, and ER-ß expressions were significantly increased in 36-week-old mice. THSG also increased oocyte numbers in aged mice compared to mice without THSG fed. Studies of qPCR and immunohistochemistry (IHC) analyses of ovaries in the aged mice groups were conducted. THSG increased gene expression of anti-Müllerian hormone (AMH), a biomarker of oocyte number, and protein accumulation in 40-week-old mice. THSG increased the expression of pgc1α and atp6, mitochondrial biogenesis-related genes, and their protein expression. THSG also attenuated the fading rate of CYP11a and CYP19 associated with sex hormone synthesis. And THSG maintains a high level of ER-ß expression, thereby enhancing the sensitivity of estrogen. Our findings indicated that THSG increased or extended gene expression involved in ovarian maintenance and rejuvenation in young and aged mice. On the other hand, THSG treatments significantly maintained oocyte quantity and quality in both groups of young and aged mice compared to each age-matched control group. In conclusion, THSG can delay aging-related menopause, and the antioxidant properties of THSG may make it suitable for preventing aging-induced infertility.

Fabrication of Low-Molecular-Weight Hyaluronic Acid-Carboxymethyl Cellulose Hybrid to Promote Bone Growth in Guided Bone Regeneration Surgery: An Animal Study.

Guided bone regeneration surgery is an important dental operation used to regenerate enough bone to successfully heal dental implants. When this technique is performed on maxilla sinuses, hyaluronic acid (HLA) can be used as an auxiliary material to improve the graft material handling properties. Recent studies have indicated that low-molecular hyaluronic acid (L-HLA) provides a better regeneration ability than high-molecular-weight (H-HLA) analogues. The aim of this study was to fabricate an L-HLA-carboxymethyl cellulose (CMC) hybrid to promote bone regeneration while maintaining viscosity. The proliferation effect of fabricated L-HLA was tested using dental pulp stem cells (DPSCs). The mitogen-activated protein kinase (MAPK) pathway was examined using cells cultured with L-HLA combined with extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 inhibitors. The bone growth promotion of fabricated L-HLA/CMC hybrids was tested using an animal model. Micro-computer tomography (Micro-CT) and histological images were evaluated quantitatively to compare the differences in the osteogenesis between the H-HLA and L-HLA. Our results show that the fabricated L-HLA can bind to CD44 on the DPSC cell membranes and affect MAPK pathways, resulting in a prompt proliferation rate increase. Micro CT images show that new bone formation in rabbit calvaria defects treated with L-HLA/CMC was almost two times higher than in defects filled with H-HLA/CMC (p < 0.05) at 4 weeks, a trend that remained at 8 weeks and was confirmed by HE-stained images. According to these findings, it is reasonable to conclude that L-HLA provides better bone healing than H-HLA, and that the L-HLA/CMC fabricated in this study is a potential candidate for improving bone healing efficiency when a guided bone regeneration surgery was performed.

Heteronemin and Tetrac Induce Anti-Proliferation by Blocking EGFR-Mediated Signaling in Colorectal Cancer Cells.

Overexpressed EGFR and mutant K-Ras play vital roles in therapeutic resistance in colorectal cancer patients. To search for an effective therapeutic protocol is an urgent task. A secondary metabolite in the sponge Hippospongia sp., Heteronemin, has been shown to induce anti-proliferation in several types of cancers. A thyroxine-deaminated analogue, tetrac, binds to integrin αvß3 to induce anti-proliferation in different cancers. Heteronemin- and in combination with tetrac-induced antiproliferative effects were evaluated. Tetrac enhanced heteronemin-induced anti-proliferation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC). Heteronemin and tetrac arrested cell cycle in different phases. Combined treatment increased the cell accumulation in sub-G1 and S phases. The combined treatment also induced the inactivation of EGFR signaling and downregulated the phosphorylated ERK1/2 protein in both cell lines. Heteronemin and the combination showed the downregulation of the phosphorylated and total PI3K protein in HT-29 cells (KRAS WT CRC). Results by NanoString technology and RT-qPCR revealed that heteronemin and combined treatment suppressed the expression of EGFR and downstream genes in HCT-116 cells (KRAS MT CRC). Heteronemin or combined treatment downregulated genes associated with cancer progression and decreased cell motility. Heteronemin or the combined treatment suppressed PD-L1 expression in both cancer cell lines. However, only tetrac and the combined treatment inhibited PD-L1 protein accumulation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC), respectively. In summary, heteronemin induced anti-proliferation in colorectal cancer cells by blocking the EGFR-dependent signal transduction pathway. The combined treatment further enhanced the anti-proliferative effect via PD-L1 suppression. It can be an alternative strategy to suppress mutant KRAS resistance for anti-EGFR therapy.

Toxicologic Concerns with Current Medical Nanoparticles.

Nanotechnology is one of the scientific advances in technology. Nanoparticles (NPs) are small materials ranging from 1 to 100 nm. When the shape of the supplied nanoparticles changes, the physiological response of the cells can be very different. Several characteristics of NPs such as the composition, surface chemistry, surface charge, and shape are also important parameters affecting the toxicity of nanomaterials. This review covered specific topics that address the effects of NPs on nanomedicine. Furthermore, mechanisms of different types of nanomaterial-induced cytotoxicities were described. The distributions of different NPs in organs and their adverse effects were also emphasized. This review provides insight into the scientific community interested in nano(bio)technology, nanomedicine, and nanotoxicology. The content may also be of interest to a broad range of scientists.

The power of heteronemin in cancers.

Heteronemin (Haimian jing) is a sesterterpenoid-type natural marine product that is isolated from sponges and has anticancer properties. It inhibits cancer cell proliferation via different mechanisms, such as reactive oxygen species (ROS) production, cell cycle arrest, apoptosis as well as proliferative gene changes in various types of cancers. Recently, the novel structure and bioactivity evaluation of heteronemin has received extensive attention. Hormones control physiological activities regularly, however, they may also affect several abnormalities such as cancer. L-Thyroxine (T4), steroid hormones, and epidermal growth factor (EGF) up-regulate the accumulation of checkpoint programmed death-ligand 1 (PD-L1) and promote inflammation in cancer cells. Heteronemin suppresses PD-L1 expression and reduces the PD-L1-induced proliferative effect. In the current review, we evaluated research and evidence regarding the antitumor effects of heteronemin and the antagonizing effects of non-peptide hormones and growth factors on heteronemin-induced anti-cancer properties and utilized computational molecular modeling to explain how these ligands interacted with the integrin αvß3 receptors. On the other hand, thyroid hormone deaminated analogue, tetraiodothyroacetic acid (tetrac), modulates signal pathways and inhibits cancer growth and metastasis. The combination of heteronemin and tetrac derivatives has been demonstrated to compensate for anti-proliferation in cancer cells under different circumstances. Overall, this review outlines the potential of heteronemin in managing different types of cancers that may lead to its clinical development as an anticancer agent.

Partial carbonization of quercetin boosts the antiviral activity against H1N1 influenza A virus.

Inflenza A viruses (IAVs) are highly transmissible and pathogenic Orthomyxoviruses, which have led to worldwide outbreaks and seasonal pandemics of acute respiratory diseases, causing serious threats to public health. Currently used anti-influenza drugs may cause neurological side effects, and they are increasingly less effective against mutant strains. To help prevent the spread of IAVs, in this work, we have developed quercetin-derived carbonized nanogels (CNGsQur) that display potent viral inhibitory, antioxidative, and anti-inflammatory activities. The antiviral CNGsQur were synthesized by mild carbonization of quercetin (Qur), which successfully preserved their antioxidative and anti-inflammatory properties while also contributed enhanced properties, such as water solubility, viral binding, and biocompatibility. Antiviral assays of co-treatment, pre-treatment, and post-treatment indicate that CNGsQur interacts with the virion, revealing that the major antiviral mechanism resulting in the inhibition of the virus is by their attachment on the cell surface. Among them, the selectivity index (SI) of CNGsQur270 (>857.1) clearly indicated its great potential for clinical application in IAVs inhibition, which was much higher than that of pristine quercetin (63.7) and other clinical drugs (4-81). Compared with quercetin at the same dose, the combined effects of viral inhibition, antioxidative and anti-inflammatory activities impart the superior therapeutic effects of CNGsQur270 aerosol inhalation in the treatment of IAVs infection, as evidenced by a mouse model. These CNGsQur effectively prevent the spread of IAVs and suppress virus-induced inflammation while also exhibiting good in vivo biocompatibility. CNGsQur shows much promise as a clinical therapeutic agent against infection by IVAs.

Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein.

Japanese encephalitis is a mosquito-borne disease caused by the Japanese encephalitis virus (JEV) that is prevalent in Asia and the Western Pacific. Currently, there is no effective treatment for Japanese encephalitis. Curcumin (Cur) is a compound extracted from the roots of Curcuma longa, and many studies have reported its antiviral and anti-inflammatory activities. However, the high cytotoxicity and very low solubility of Cur limit its biomedical applications. In this study, Cur carbon quantum dots (Cur-CQDs) were synthesized by mild pyrolysis-induced polymerization and carbonization, leading to higher water solubility and lower cytotoxicity, as well as superior antiviral activity against JEV infection. We found that Cur-CQDs effectively bound to the E protein of JEV, preventing viral entry into the host cells. In addition, after continued treatment of JEV with Cur-CQDs, a mutant strain of JEV was evolved that did not support binding of Cur-CQDs to the JEV envelope. Using transmission electron microscopy, biolayer interferometry, and molecular docking analysis, we revealed that the S123R and K312R mutations in the E protein play a key role in binding Cur-CQDs. The S123 and K312 residues are located in structural domains II and III of the E protein, respectively, and are responsible for binding to receptors on and fusing with the cell membrane. Taken together, our results suggest that the E protein of flaviviruses represents a potential target for the development of CQD-based inhibitors to prevent or treat viral infections.