PC12 Cells Research Articles

Chemical Composition, Antifungal, Antibacterial, Antioxidant, Antiviral and Cytotoxic Activities of Ruta chalepensis L. Fixed Oil from Saudi Arabia

An aromatic plant is called Ruta chalepensis L. known locally as “Fidjel,” grows in rocky, arid places. Its pharmacological activities are pleiotropic. The goal of the present investigation was to use GCMS and HPLC analysis to identify the chemical constituents of oil extracted from Ruta chalepensis L. and assess its antibacterial, antifungal, antioxidant, antiviral, and anticancer properties. Linoleic acid was the most predominant acid found in Ruta chalepensis L. oil, then oleic acid, palmitic acid, and linolenic acid. 13.64 μg/mL of tocopherol (α-, β-, and γ-tocopherol) was identified. The primary phytosterols are β-sitosterol and campesterol. At 200 μL/mL of Ruta chalepensis L. oil, phenolic components rated 84.4 GAE/mL and had 94.0% antioxidant activity. Zone inhibition efficacy of Ruta chalepensis L. oil against microbial strains, particularly E. coli with a diameter of 42.3 mm, was demonstrated. MBC (30 μL/mL and 40 μL/mL) are the bactericidal action against E. coli and S. aureus, while MIC bacteriostatic (30 μL/mL) was also demonstrated. However, Ruta chalepensis L. oil was ineffective against Saccharomyces cervisia and fungal strains. Weak inhibitory impact of Ruta chalepensis L. oil was observed against the PC-3 (prostate cancer) cell line. Nonetheless, it had a significant inhibitory impact on the A2780 (ovarian cancer) cell line. At 100 μg/mL of oil, Ruta chalepensis L. oil showed a low antiviral impact (7.93±2.03%) against the herpes simplex virus type 2 (HSV-2). Oil from Ruta chalepensis L. is a promising option for the medical management of non- transmissible illnesses, since it is wealthy in antioxidants and bioactive substances.

A lighting up NIR fluorescent sensing assay for norepinephrine and its application in the imaging of depressed mice brain

Norepinephrine (NE) is a neurotransmitter that plays important roles in the monitoring of depression. The significant decrease in its content was positively correlated with the severity of depression. Therefore, the accurate detection of NE is particularly important for tracking the onset of depression. Herein, a lighting up near-infrared (NIR) fluorescent probe Cy-TPC, with both of the excitation and emission wavelength located in NIR region, was designed for the specifically monitor NE. Cy-TPC itself emits almost no fluorescence upon excited at 690 nm. After the incubation with NE, the β-hydroxyethylamine group of NE will attack the carbonate of Cy-TPC, undergo a nucleophilic substitution reaction, and finally release the fluorophore Cy-OH, which leading to the generation of NIR fluorescence at 768 nm. Cy-TPC exhibits high selectivity and acceptable sensitivity (with a LOD calculated as 5.01 μM) for the detection of NE, laying the foundation for its application in biological samples. The subsequent biological imaging experiments indicated that Cy-TPC could be used to monitor the content of NE in PC-12 cells and was successfully applied to the imaging of NE in depressed mice brain.

Chemical Constituents of the Fruits of Cornus Officinalis and Evaluation of their Neuroprotective Activity.

The phytochemical investigation of the fruits of Cornus officinalis yielded a new phenolic acid derivative, neophenolic acid A (1), and a novel flavonoid glycoside, (2R)-naringenin-7-O-β-(6''-galloyl-glucopyranoside) (2 a), along with six known flavonoid glycosides (2 b-7). Their structures were determined by 1D, 2D NMR and HRESIMS data. The absolute configuration of 1 was established by ECD analysis. Compounds 1- 7 were evaluated for their neuroprotective activities against corticosterone (CORT)-induced injury in PC-12 cells. Compounds 1, 2 a, 2 b, 5, and 6 exhibited neuroprotective activities against CORT-induced neurotoxicity in PC-12 cells. The underlying mechanism study suggested that compounds 1, 2 a, 2 b, 5, and 6 were able to attenuate CORT-induced apoptosis and damage, increase the levels of MMP and decrease Ca2+ inward flow in PC-12 cells.

Antidepressant Effect of Enzymatic Porcine Placenta Hydrolysate in Repeated Immobilization Stress-Induced Ovariectomized Female Mice.

When postmenopausal women are under stress conditions, this exacerbates mood disorders and issues with neuroimmune systems. The porcine placenta is known to relieve menopausal depression in clinical trials, but its underlying mechanisms for depression and anti-inflammatory functions remain poorly defined. The present study was designed to examine the anti-inflammatory effects of enzymatic porcine placenta hydrolysate (EPPH) on LPS-induced levels of nitric oxide (NO), prostaglandin E2 (PGE2), corticosterone (CORT), and pro-inflammatory cytokine interleukin-1 beta (IL-1β) in RAW 264.7 macrophage cells. In addition, the neurite outgrowth of PC12 cells was evaluated to examine the effects of EPPH on neurite growth. To mimic the symptoms of women with menopause-related depression, a stressed ovariectomized (OVX) female mouse model was used to evaluate the antidepressant effects of EPPH. The female mice were randomly divided into five groups: (1) the sham-operated (Sham) group, (2) the OVX + repeated stress + saline-treated (OVX + ST) group, (3) the OVX + repeated stress + estradiol (0.2 mg/kg)-treated (positive control) group, (4) the OVX + repeated stress + EPPH (300 mg/kg)-treated (300) group, and (5) the OVX + repeated stress + EPPH (1500 mg/kg)-treated (1500) group. Female mice were OVX and repeatedly immobilization-stressed for 2 weeks (2 h/day). A tail suspension test was conducted on the 13th day, followed by the forced swimming test on the 14th day to assess the antidepressant effects of EPPH. After the behavioral tests, the levels of CORT, PGE2, and IL-1β were evaluated. In addition, c-Fos expression in the paraventricular nucleus (PVN) was evaluated using immunohistochemistry. The concentrations of NO, PGE2, and IL-1β stimulated by LPS were significantly reduced via the addition of EPPH to RAW 264.7 cells. EPPH significantly promoted neurite outgrowth in PC12 cells compared to that of the controls. In the tail suspension test, the duration of immobility was reduced in mice treated with EPPH 1500 compared to the OVX + ST group. The EPPH 1500 group had significantly decreased levels of c-Fos-positive neurons in the PVN and reduced levels of CORT and IL-1β in the serum of the Sham group. These results suggested that the high dose of EPPH administration induced the antidepressant-like effect in the ovariectomized mice with repeated stress via downregulating the levels of CORT, IL-1β, and PGE2 in the serum through reducing the expression of c-Fos in the PVN regions.

A PEDOT: PSS/GO fiber microelectrode fabricated by microfluidic spinning for dopamine detection in human serum and PC12 cells.

Rapid and accurate in situ determinationof dopamine is of great significance in the study of neurological diseases. In this work, poly (3,4-ethylenedioxythiophene): poly (styrenesulfonic acid) (PEDOT: PSS)/graphene oxide (GO) fibers were fabricated by an effective method based on microfluidic wet spinning technology. The composite microfibers with stratified and dense arrangement were continuously prepared by injecting PEDOT: PSS and GO dispersion solutions into a microfluidic chip. PEDOT: PSS/GO fiber microelectrodes with high electrochemical activity and enhanced electrochemical oxidation activity of dopamine were constructed by controlling the structure composition of the microfibers with varying flow rate. The fabricated fiber microelectrode had a low detection limit (4.56 nM) and wide detection range (0.01-8.0 µM) for dopamine detection with excellent stability, repeatability, and reproducibility. In addition, the PEDOT: PSS/GO fiber microelectrode prepared was successfully used for the detection of dopamine in human serum and PC12 cells. The strategy for the fabrication of multi-component fiber microelectrodes isa new and effective approach for monitoring the intercellular neurotransmitter dopamine and has highpotential as an implantable neural microelectrode.

Preparation, structural characterization and protective effect on PC12 cells of polysaccharides from the stipe of Morchella esculenta

Morchella esculenta is a type of edible mushroom used in traditional medicine, which is popular among consumers, and the stipe of M. esculenta is the industrial waste of M. esculenta. This study reports the isolation and purification of a novel polysaccharide (MP-C) from the stipe of M. esculenta, and we analyzed its chemical structure. The results showed that→4)-α-D-Glcp-(1→,T-α-D-Glcp,→4,6)-α-D-Glcp-(1→,→6)-α-D-Manp-(1→,→3)-α-D-Glcp-(1→and→3)-α-D-Manp-(1→) comprise the main chain of MP-C. More importantly, reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels within cells were all dramatically reduced by MP-C, while superoxide dismutase (SOD) levels were elevated. Western blot results showed that MP-C increased the expression level of Bcl-2, while inhibiting the expression of Caspase-3 and BAX. In addition, we found that the PI3K/Akt pathway was involved in the regulation of hydrogen peroxide-induced apoptosis in PC12 cells by MP-C. In conclusion, MP-C attenuated the oxidative stress and apoptosis induced by hydrogen peroxide in PC12 cells. This study for the development and utilization of the stipe of Morchella esculenta stipes provides certain theoretical basis.

Deciphering the molecular mechanism of long non-coding RNA HIF1A-AS1 regulating pancreatic cancer cells

Background: HIF1A-AS1, an antisense transcript of HIF1α gene, is a 652-bp LncRNA that is globally expressed in multiple tissues of animals. Recent evidence indicated that HIF1A-AS1 was involved in tumorigenesis of several types of cancer. However, the role of lncRNA in PC has not been reported, and the molecular mechanism remains elusive. Results: In order to investigate the role of HIF1A-AS1 in PC, it was overexpressed in some PC cell lines (PANC-1, PATU8988 and SW1990), and a series of experiments including cell viability detection, flow cytometry, transwell migration, clone formation and wound healing were performed. Functionally, the results indicated that overexpression of HIF1A-AS1 could greatly inhibit proliferation and migration and promote apoptosis of PC cells. Moreover, the isobaric tags for relative and absolute quantification (iTRAQ) quantitative proteomics analysis was implemented to explore the underlying mechanism and the results indicated that OE of HIF1A-AS1 globally affected the expression levels of multiple proteins associated with metabolism of cancer. At last, the network analysis revealed that most of these differentially expressed proteins (DEPs) were integrated and severed essential roles in regulatory function. In view of this, we guessed HIF1A-AS1 overexpression induced the dysfunction of metabolism and disordered proteins’ translation, which may account for its excellent tumour suppressor effect. Conclusions: HIF1A-AS1 altered the cell function of PC cell lines via affecting the expression of numerous proteins. In summary, HIF1A-AS1 may exhibit a potential therapeutic effect on PC, and our study provided useful information in this filed.

Astragaloside IV mediates radiation-induced neuronal damage through activation of BDNF-TrkB signaling

BackgroundElectromagnetic radiation is relevant to human life, and radiation can trigger neurodegenerative diseases by altering the function of the central nervous system through oxidative stress, mitochondrial dysfunction, and protein degradation. Astragaloside IV (AS-IV) is anti-oxidative, anti-apoptotic, activates the BDNF-TrkB pathway and enhances synaptic plasticity in radiated mice, which can exert its neuroprotection. However, the exact molecular mechanisms are still unclear. PurposeThis study investigated whether AS-IV could play a neuroprotective role by regulating BDNF-TrkB pathway in radiation damage and its underlying molecular mechanisms. MethodsTransgenic mice (Thy1-YFP line H) were injected with AS-IV (40 mg/kg/day body weight) by intraperitoneal injection daily for 4 weeks, followed by X-rays. PC12 cells and primary cortical neurons were also exposed to UVA after 24 h of AS-IV treatment (25 μg/ml and 50 μg/ml) in vitro. The impact of radiation on learning and cognitive functions was visualized in the Morris water maze assay. Subsequently, Immunofluorescence and Golgi-Cox staining analyses were utilized to investigate the structural damage of neuronal dendrites and the density of dendritic spines. Transmission electron microscopy was performed to examine how the radiation affected the ultrastructure of neurons. Finally, western blotting analysis and Quantitative RT-PCR were used to evaluate the expression levels and locations of proteins in vitro and in vivo. ResultsRadiation induced BDNF-TrkB signaling dysregulation and decreased the levels of neuron-related functional genes (Ngf, Bdnf, Gap-43, Ras, Psd-95, Arc, Creb, c-Fos), PSD-95 and F-actin, which subsequently led to damage of neuronal ultrastructure and dendrites, loss of dendritic spines, and decreased dendritic complexity index, contributing to spatial learning and memory deficits. These abnormalities were prevented by AS-IV treatment. In addition, TrkB receptor antagonists antagonized these neuroprotective actions of AS-IV. 7,8-dihydroxyflavone and AS-IV had neuroprotective effects after radiation. ConclusionAS-IV inhibits morphological damage of neurons and cognitive dysfunction in mice after radiation exposure, resulting in a neuroprotective effect, which were mediated by activating the BDNF-TrkB pathway.

3'-Daidzein Sulfonate Sodium Protects against Glutamate-induced Neuronal Injuries by Regulating NMDA Receptors.

It was previously found that 3'-Daidzein Sulfonate Sodium (DSS) exhibits protective effects on Cerebral Ischemia-Reperfusion Injury (CI/RI). This study aimed to explore the underlying molecular mechanisms involved in the neuroprotective effects of DSS against ischemic stroke. In this study, rats with transient middle cerebral artery occlusion (tMCAO) were used as an in vivo model, whereas PC12 cells treated with glutamate alone and rat primary cortical neurons treated with the combination of glutamate and glycine were used as in vitro models. Cell viability and lactate dehydrogenase (LDH) release were used to evaluate cell injury. Cell apoptosis was determined by flow cytometry. Quantitative polymerase chain reaction (qPCR), Western blotting, and immunofluorescent staining methods were used to determine the mRNA expressions and protein levels and location. It was found that DSS significantly suppressed the impaired viability of PC12 cells induced by glutamate. DSS also increased cell viability while reducing the LDH release and apoptosis in primary cortical neurons injured by glutamate and glycine. In addition, DSS decreased GluN2B subunit expression while enhancing the expressions of GluN2A subunit and PSD95 in tMCAO rats' brains. This study demonstrated that DSS protects against excitotoxic damage in neurons by regulating the expression of NMDA receptors and PSD95 in the brain with cerebral ischemia-reperfusion injury. Our findings provide experimental evidence for the potential clinical administration of DSS in ischemic stroke.

Janus Dendrimers as Nanocarriers of Ibuprofen, Chlorambucil and their Anticancer Activity.

Janus Dendrimer represents a novel class of synthetic nanocarriers. Since it is possible to introduce multiple drugs and target moieties, this helps the designing of new biocompatible forms with pharmacological activities comprised of different drugs with tailor-made functionalities, such as anticancer and nonsteroidal anti-inflammatory, which could improve the anticancer activity with less toxicity. This study aimed to determine the anticancer activity of the Janus dendrimers formed by two dendrons. One dendron conjugates with chlorambucil, and the other dendron conjugates with Ibuprofen. The cytotoxicity of the drug carriers was determined by the sulforhodamine B (SRB) assay for three cell lines. PC-3 (human prostatic adenocarcinoma), HCT-15 (human colorectal adenocarcinoma), MFC-7 (human breast cancer) and the COS-7 African green monkey kidney (used as a control) cell lines were seeded into 96-well plates at a density of 5x103 cells/well and cultured for 24 h before use. All the obtained compounds were characterized by 1H and 13C NMR one and two dimensions, UVvis, FTIR, MALDI-TOF, Electrospray mass, and FAB+. Microscopic images were taken in an Inverted microscope Nikon, Diaphot 300, 10x4 in culture medium. Janus dendrimers (G1 and G2) were synthesized via an azide-alkyne click-chemistry reaction attaching on one face dendrons with ibuprofen molecules and, on the other face, attached a chlorambucil- derivative. The IC50 behavior of the conjugates of the first and second generations showed anticancer activity against PC-3, HCT-15, and MFC-7 cell lines. The second generation was more active against PC-3, HCT-15 and MFC-7 with IC50 of 3.8±0.5, 3.0±0.2 and 3.7 ± 1.1 mM, respectively. The new Janus dendrimers with anticancer chlorambucil and nonsteroidal antiinflammatory Ibuprofen can improve the anticancer activity of chlorambucil with less toxicity. Now, we are working on the synthesis of new Janus dendrimers using the most effective and fine methods. Moreover, we hope that we shall be able to obtain different generations that are more selective against cancer cells.

Antidepressant-like effects of Cimicifuga dahurica (Turcz.) Maxim. via modulation of monoamine regulatory pathways

Sheng-ma is recorded in the Compendium of Materia Medica and mainly originates from the rhizomes of Cimicifuga dahurica (Turcz.) Maxim. (CD), Cimicifuga heracleifolia Kom. and Cimicifuga foetida L. The alcoholic extract of Cimicifuga foetida L. (Brand name: Ximingting®) has been approved for the treatment of perimenopausal symptoms accompanying hot flash, depression and anxiety in China. However, there's no further study about the antidepressant-like effects of C. dahurica (CD). The aim of this study is to investigate the antidepressant-like effect of CD extracted by 75% ethanol and its possible mechanisms.The neuro-protective effects of CD on injured PC12 cells induced by corticosterone was measured firstly. Then, forced swim test (FST), tail suspension test (TST), reserpine-induced hypothermia, 5-hydroxytryptophan (5-HTP) induced head twitch response in mice and chronic unpredictable mild stress (CUMS) on sucrose preference tests were executed. Moreover, the potential mechanisms were explored by measuring levels of monoamine neurotransmitter in mice frontal cortex and hippocampus, testing monoamine oxidase enzyme A (MAO-A) activities in the brains of CUMS-exposed mice. Results showed that CD (60, 120 mg/kg) can significantly decreased the immobility period in FST and TST in mice without affecting locomotor activity. CD (30 mg/kg, 60 mg/kg, 120 mg/kg) could significantly counteracted reserpine-induced hypothermia and increased the number of head-twitches in 5-HTP induced head twitch response. It was also found that the monoamine neurotransmitter levels in the hippocampus and frontal cortex were significantly increased in 60 mg/kg and 120 mg/kg CD treated mice. In addition, CD (60 and 120 mg/kg) significantly inhibited MAO-A after 6-week CUMS exposure. CD can effectively produce an antidepressant-like effect, which involved with modulation of monoamine regulatory pathways.

Superhydrophobic synergistic antibacterial ZrO2-based surfaces with tertiary hierarchical structures fabricated by femtosecond laser texturing and surface modification

Zirconia (ZrO2) is a hard and brittle dental implant material without anti-infective property. This work reports the preparation of a tertiary micro-nano hierarchical structure on a ZrO2 surface via femtosecond laser texturing combined with magnetron sputtering deposition of an Ag layer (Ag/ZrO2), aiming to achieve a superhydrophobic synergistic antibacterial effect. Laser-scanning pitch and Ag layer thickness were systematically optimized for obtaining the tertiary hierarchical structure. The wettabilities, antibacterial properties and durabilities of various ZrO2 and stearic acid modified Ag/ZrO2 (S-Ag/ZrO2) surfaces were further tested and comparatively analyzed. The results revealed that the optimal process parameters were a laser-scanning pitch of 30 μm and an Ag layer thickness of 100 nm. The as-obtained S-Ag/ZrO2 sample displayed a tertiary micro-nano hierarchical structure, which was featured by a periodic regular conical micro-convex structure covered with ZrO2 nano-protrusions and Ag nanoparticles. This structure could not only greatly reduce the solid-liquid contact area to achieve outstanding superhydrophobicity and durability, it could also sustainably release bacteria-killing Ag+ to obtain an antibacterial ratio of 95.1 % and ensure a long-term antibacterial effect. In addition, the optimal S-Ag/ZrO2 sample having this structure showed a PC12 cell survival rate of up to 81.75 %, demonstrating its good biocompatibility. This work may be of great inspiration and reference for the expansion of the use of ZrO2 in dentistry.

GRN knockdown regulates the expression and alternative splicing of genes associated with aphasia-related diseases in PC12 cells

BackgroundPrior research has shown that granulin precursor (GRN, also termed PGRN) is closely linked to aphasia. However, there has been little research on the mechanism of action of GRN in post-stroke aphasia (PSA). MethodsIn this study, RT-qPCR was used to identify variations in gene expression, while RNA sequencing (RNA-seq) was utilized to acquire transcriptional profiles. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were employed for bioinformatics analysis. ResultsGRN was considerably more active in PSA subjects. After silencing the GRN, 197 transcripts had differential expression, and 237 alternative splicing events (ASEs) were substantially affected. The analysis of differentially expressed genes (DEGs) using GO and KEGG approaches showed that these genes have various molecular functions and are significantly enriched in metabolic signaling pathways. Regarding Alternative Splicing (AS), the GO and KEGG analyses revealed numerous functional genes involved in transcription and metabolism. ConclusionsThe knockdown of GRN has been shown to be associated with alterations in transcription, metabolism, and ASEs, potentially impacting transcriptional and metabolic pathways through its involvement in AS. Furthermore, GRN knockdown is associated with nervous system disease-related gene transcription and AS processes, as well as its involvement in G protein-coupled receptor (GPCR) and wingless/integrated (Wnt) signaling pathways, which impact the initiation and resolution of PSA.

Dysregulated MiR-223-5p Modulates Inflammation and Oxidative Stress in Traumatic Spinal Cord Injury

ABSTRACT Aim This study aimed to evaluate the miR-223-5p expression in patients with spinal cord injury (SCI) and to determine its role in the pathogenesis of SCI. Methods The serum miR-223-5p levels were analyzed using quantitative real-time polymerase chain reaction. The diagnostic accuracy of miR-223-5p was evaluated using the receiving operating characteristic curves. LPS-induced PC12 cells were established as an in vitro inflammatory cell model. Cell apoptosis, inflammation and oxidative stress were examined. The SCI rat model was constructed to evaluate the effects of miR-223-5p on inflammatory response and motor function in rats. Results MiR-223-5p expression was upregulated in SCI patients. MiR-223-5p expression in the complete SCI group was significantly higher than that in incomplete SCI group. ROC analysis showed that miR-223-5p can distinguish SCI patients from healthy volunteers. In vitro experiments demonstrated that LPS upregulated apoptosis and inflammation in PC12 cells. Treatment with miR-223-5p inhibitor alleviated the changes in LPS-induced PC12 cells . Inhibition of miR-223-5p can alleviate the activation of inflammatory response and the effects of SCI on the motor function in rats. Conclusions MiR-223-5p is a potential diagnostic marker for SCI, and it can promote the SCI progression by regulating nerve cell survival, inflammation, and oxidative stress.

Identification and validation of the TRHDE-AS1/hsa-miR-449a/ADAMTS5 axis as a novel prognostic biomarker in prostate cancer.

Despite advancements in cancer research, the prognostic implications of competing endogenous RNA (ceRNA) networks in prostate cancer (PCa) remain incompletely understood. This study aimed to elucidate the prognostic relevance of ceRNA networks in PCa, utilizing a comprehensive bioinformatics approach alongside experimental validation. After searching The Cancer Genome Atlas (TCGA) database, RNA sequencing (RNA-Seq) data were extracted to identify differentially expressed RNAs (DERs) between 491 PCa samples and 51 normal prostate tissues, following which a comprehensive bioinformatics strategy was implemented to construct a ceRNA network. An optimal prognostic signature comprising these DERs was then established and validated using TCGA data. In addition, functional validation was performed through RNA pull-down, dual-luciferase reporter assays, quantitative real-time PCR, and western blot analysis conducted in PC-3 and DU145 cell lines, thereby complementing the bioinformatics analysis. A total of 613 DERs, comprising 103 long noncoding RNAs (lncRNAs), 60 microRNAs (miRNAs), and 450 messenger RNAs (mRNAs), were identified and utilized in constructing a ceRNA network, which encompassed 23 lncRNAs, 9 miRNAs, and 52 mRNAs. An optimal prognostic signature was established, including VPS9D1 antisense RNA 1 (VPS9D1-AS1), miR-449a, cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1), targeting protein for Xklp2 (TPX2), solute carrier family 7 member 11 (SLC7A11), copine7 (CPNE7), and maternal embryonic leucine zipper kinase (MELK), yielding area under the curve (AUC) values exceeding 0.8 across training, validation, and entire datasets. Our experiments results revealed an interaction between lncRNA TRHDE antisense RNA 1 (TRHDE-AS1) and miR-449a and that miR-449a could target the ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) mRNA. Knockdown of miR-449a significantly impeded cell proliferation, G1/S transition, migration and invasion, and promoted apoptosis in PC-3 and DU145 cells. Furthermore, knockdown of miR-449a notably downregulated protein expression of CDK4, cyclin D1, N-cadherin and vimentin, while upregulating protein expression of cleaved caspase-3 and E-cadherin. This study contributes to a deeper understanding of the prognostic-linked ceRNA network in PCa, providing fundamental insights that could improve diagnostic and therapeutic approaches for PCa management.

Synergy between Laminin-Derived Elastin-like Polypeptides (LELPs) Optimizes Cell Spreading.

A major component of the extracellular matrix (ECM), laminins, modulates cells via diverse receptors. Their fragments have emerging utility as components of "ECM-mimetics" optimized to promote cell-based therapies. Recently, we reported that a bioactive laminin peptide known as A99 enhanced cell binding and spreading via fusion to an elastin-like polypeptide (ELP). The ELP "handle" serves as a rapid, noncovalent strategy to concentrate bioactive peptide mixtures onto a surface. We now report that this strategy can be further generalized across an expanded panel of additional laminin-derived elastin-like polypeptides (LELPs). A99 (AGTFALRGDNPQG), A2G80 (VQLRNGFPYFSY), AG73 (RKRLQVQLSIRT), and EF1m (LQLQEGRLHFMFD) all promote cell spreading while showing morphologically distinct F-actin formation. Equimolar mixtures of A99:A2G80-LELPs have synergistic effects on adhesion and spreading. Finally, three of these ECM-mimetics promote the neurite outgrowth of PC-12 cells. The evidence presented here demonstrates the potential of ELPs to deposit ECM-mimetics with applications in regenerative medicine, cell therapy, and tissue engineering.

HSP70 protects PC12 cells against TBHP-induced apoptosis and oxidative stress by activating the Nrf2/HO-1 signaling pathway.

HSP70 exhibits neuroprotective, antioxidant, and anti-apoptotic properties, which are crucial in preventing spinal cord injury (SCI) induced by oxidative stress and apoptosis. In this study, we assessed the potential protective effects and underlying mechanisms of HSP70 on tert-butyl hydroperoxide (TBHP)-damaged PC12 cells in an in vitro model of SCI. To establish the model, PC12 cells were subjected to oxidative damage induced by TBHP, followed by overexpression of HSP70. Cell viability was assessed using the CCK8 kit, intracellular reactive oxygen species level was evaluated using a commercial kit, cell apoptosis was detected using the Annexin V-APC/7-ADD Apoptosis Detection Kit, and the oxidative stress level was determined using SOD and MDA assay kits. Western blot analysis was used to detect the expression levels of Bax, cleaved caspase-3, and Bcl-2 proteins. Furthermore, immunofluorescence staining and Western bolt were used to detect the expression levels of proteins associated with the Nrf2/HO-1 signaling pathway. We found that HSP70 overexpression reduced apoptosis and oxidative stress in TBHP-induced PC12 cells. Furthermore, it activated the Nrf2/HO-1 signaling pathway. In addition, the Nrf2 inhibitor ML385 attenuated the protective effects of HSP70 on TBHP-induced PC12 cells. In conclusion, HSP70 can partially alleviate TBHP-induced apoptosis and oxidative stress in PC12 cells by promoting the Nrf2/HO-1 signaling pathway.

Screening of monoamine oxidase B inhibitors in Tibetan strawberry by ligand fishing based on enzyme functionalized cellulose filter paper

Tibetan strawberry (Fragaria nubicola) is a wild medicinal and edible plant in Tibet possessing various health benefits such as neuroprotection and anti-oxidation. However, there has been little study reported on its chemical constituents. To investigate the inhibitors of monoamine oxidase B (MAO-B) in Tibetan strawberry, we immobilized the enzyme onto cellulose filter paper for the first time to develop a new screening method. Two known glycosides (compounds 1 and 2) and one new iridoid glucoside (Compound 3) were fished out by this method, which was found to effectively inhibit MAO-B with IC50 values of 16.95 ± 0.93, 24.69 ± 0.20, and 46.77 ± 0.78 μM, respectively. Molecular docking and kinetic analysis were performed to reveal the inhibition mechanism of these compounds. Furthermore, compound 1 exhibited neuroprotective effects against 6-OHDA-induced injury on PC12 cells. The developed method exhibits the advantages of rapidness and effectiveness in screening of MAO-B inhibitors from complex herbal extracts.

In Vitro Biological and GC-MS Analysis of Whole Plant Calotropis procera

Calotropis procera is a medicinal, traditional, and therapeutic plant in Pakistan. In this research study, the biological activities, for instance, anticancer, antileishmanial, antibacterial, antifungal, anti-inflammatory, and brine shrimp lethality assay and GC-MS are studied. MTT assay, antileishmanial bioassay, microplate Alamar Blue assay, agar tube dilution method, oxidative burst assay using chemiluminescence technique, B-hatching techniques, and triple quadrupole acquisition method MS parameters were the methods used for anticancer, antileishmanial, antibacterial, antifungal, anti-inflammatory, brine shrimp lethality assay, and gas chromatography-mass spectrometry. Whole plant methanol extract of Calotropis procera (WMECP) inhibited 69.1% of the growth of HeLa cell line with an IC50 value of 3.1 ± 0.4 and whole plant n-hexane fraction of Calotropis procera (WHFCP) and whole plant and aqueous fraction of Calotropis procera (WAFCP) inhibited the growth by 70.2% and 65.2% with IC50 values of 5.0 ± 0.3 and 17.1 ± 1.0. Whole plant methanol extract of Calotropis procera (WMECP) inhibited 70.1% of the growth of the PC3 cell line with an IC50 value of 5.1 ± 0.3 and whole plant n-hexane fraction of Calotropis procera (WHFCP) and whole plant aqueous fraction of Calotropis procera (WAFCP) inhibited 61.6% and 59.7% with IC50 values of 3.7 ± 0.5 and 16.4 ± 1.0. None of the extract and fractions of Calotropis procera showed anticancer activities against the 3T3 cell line. None of the extract and fractions of Calotropis procera showed antileishmanial, antibacterial, antifungal, and anti-inflammatory activities. Whole plant methanol extract of Calotropis procera (WMECP) exhibited lethality at the highest concentration while other fractions did not exhibit lethality. GC-MS studies revealed that the whole plant methanol extract of Calotropis procera (WMECP) consists of 11 compounds, whole plant n-hexane fraction of Calotropis procera (WHFCP) consists of 9 compounds, and whole plant aqueous fraction of Calotropis procera (WAFCP) consists of 7 compounds.

The Effect of Psoralea corylifolia (Babchi) on Neuronal Apoptosis Induced by Palmitate in PC12 Cells and its Role in Alzheimer’s Disease: A Review

Background: Psoralea corylifolia (PC) seed extract (PCE) has been extensively utilized as an herbal drug due to its favorable effects on human health. It’s extracts and active components have demonstrated a variety of biological actions including estrogenic, anticancer, antioxidant, anti-bacterial, anti-depressant, anti-inflammatory and anti-ageing properties. Purpose: A study of this medicinal herb has major constituents extracted using different plant parts has been depicted and among them, Bakuchiol has the highest ethyl acetate extract content. Methods: The mechanism behind PCE’s anti-lipotoxic activity against palmitate (PA)-induced lipotoxicity in PC12 cells was examined. Results: CE therapy not only raised the quantities of mRNA for antioxidant genes such as heme-oxygenase and nuclear factor (erythroid-derived 2)-like 2 but also lowered the production of reactive oxygen species caused by PA. Conclusion: Prenylflavonoids play a unique role in the treatment of Alzheimer’s disease (AD) and can be used as a nootropic agent. This article comprehensively enumerated the literature on the anti-apoptotic effects of PC and its potential pathogenesis in AD.