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Phaleria macrocarpa (Boerl.) is a well-known medicinal plant and have been extensively used as traditional medicine for ages in treatment of various diseases. The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) by using various conventional and modern microscopy techniques. The cytotoxicity of PMEAF treated MDA-MB-231 cells was determined through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay and CyQuant Cell Proliferation Assay after 24 h of treatment. Both results were indicated that the PMEAF is a potential anticancer agent with the average IC 50 values of 18.10 μg/mL by inhibiting the MDA-MB-231 cell proliferation. Various conventional and modern microscopy techniques such as light microscopy, holographic microscopy, transmission (TEM) and scanning (SEM) electron microscope were used for the observation of morphological changes in PMEAF treated MDA-MB-231cells for 24 h. The characteristic of apoptotic cell death includes cell shrinkage, membrane blebs, chromatin condensation and the formation of apoptotic bodies were observed. PMEAF might be the best candidate for developing more potent anticancer drugs or chemo-preventive supplements. [ABSTRACT FROM AUTHOR]

The radioprotective effect of Polyalthia longifolia was studied in mice. P. longifolia treatment showed improvement in mice survival compared to 100% mortality in the irradiated mice. Significant increases in hemoglobin concentration, and red blood cell, white blood cell and platelet counts were observed in the animals pretreated with leaf extract. Pre-irradiation administration of P. longifolia leaf extract also increased the CFU counts of the spleen colony and increased the relative spleen size. A dose-dependent decrease in lipid peroxidation levels was observed in the animals pretreated with P. longifolia . However, although the animals pretreated with P. longifolia exhibited a significant increase in superoxide dismutase and catalase activity, the values remained below normal in both liver and the intestine. Pre-irradiation administration of P. longifolia also resulted in the regeneration of the mucosal crypts and villi of the intestine. Moreover, pretreatment with P. longifolia leaf extract also showed restoration of the normal liver cell structure and a significant reduction in the elevated levels of ALT, AST and bilirubin. These results suggested the radioprotective ability of P. longifolia leaf extract, which is significant for future investigation for human applications in developing efficient, economically viable, non-toxic natural and clinically acceptable novel radioprotectors. [ABSTRACT FROM AUTHOR]

Abstract: This work establishes a general protocol for synthesizing phytosphingosines with various lengths of lipid chains. The synthetic strategy included the Wittig reaction and olefin cross-metathesis as key steps. Combining these two C–C bond formation methods provide rapid access to adequately protected phytosphingosine backbones. [Copyright &y& Elsevier]

Oral squamous cell carcinoma (OSCC) remains a significant global challenge in the medical field, accounting for approximately 300,000 incidences and 145,000 mortalities annually. Studies suggest that early cancer detection is the most vital factor in improving OSCC patient outcomes. Effective clinical diagnosis methods for early OSCC are needed urgently. OSCC biomarkers are identified to be associated with cancer progression and biosensors are devices developed to detect the presence of OSCC biomarkers to allow early cancer diagnosis. Biosensor technology has significant potential in providing rapid and accurate detection of OSCC biomarkers with high sensitivity and specificity. Biosensors have various advantages compared to conventional diagnostic methods such as being non-invasive, low-cost, and convenient. Biosensors hold the potential to be adopted as point-of-care-testing (POCT) devices by bringing biosensor technology to the patients. This review aims to provide a comprehensive review by describing and comparing different categories of OSCC biosensors based on their advantages and drawbacks. The recent obstacles and opportunities for developing effective biosensors for cancer diagnosis are summarized. • Oral squamous cell carcinoma (OSCC) remains a significant global challenge. • Effective clinical diagnosis methods for early OSCC are needed urgently. • OSCC biomarkers are identified to be associated with cancer progression. • Biosensors are devices developed to detect the presence of OSCC biomarkers. • This review described and compared different categories of OSCC biosensors. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a neurodegenerative disorder characterized by the aggregation and deposition of alpha-synuclein protein, which are pathological hallmarks. To understand the fibril formation of alpha-synuclein in Parkinson's disease, this study uses cyclic and differential pulse voltammetric measurements. These measurements analyze the electrochemical properties and behavior of alpha-synuclein during its fibril formation process. By applying a potential sweep or pulse to the alpha-synuclein sample, it is possible to gain insights into its redox activity and structural changes during fibril formation. This could lead to the development of therapeutic strategies to prevent or disrupt this pathological event in Parkinson's disease. To detect Parkinson's disease, a 15 nm sized gold conjugated antibody was used as the probe and seeded on gold interdigitated tetraelectrodes (AuIDTE). Alpha synuclein variations (fibriled and non-fibriled) were detected using phosphate-buffer saline and glycine buffer based on cyclic voltammetry and differential pulse voltammetry techniques. Discriminated by Tau protein measurement that was employed as a control. The linear regression for detecting alpha synuclein aggregation using differential pulse voltammetry was R2 = 0.9987 [y = 9E-06x - 4E-07], with a limit of detection of 10 aM, on a linear range of 1 aM-1 pM. Cyclic voltammetry determined the limit of detection of aggregated alpha synuclein to be 100 aM, with a linear relationship of R2 = 0.9939 [y = 7E-06x - 2E-06]. The sensor has excellent analytical performance in terms of detection limit, sensitivity, selectivity, repeatability, and stability. [Display omitted] • To detect Parkinson's disease, a 15 nm sized gold conjugated antibody was used. • Seeded on an integrated interdigitated tetraelectrodes and characterized. • Alpha synuclein (2 forms) detected by cyclic and differential pulse voltammetry. • Discriminated by Tau protein measurement that was employed as a control. • Limit of detections (10 and 100 aM) for normal and aggregated target were achieved. [ABSTRACT FROM AUTHOR]

Over the years a number of microscopy methods have been developed to assess the changes in cells. Some non-invasive techniques such as holographic digital microscopy (HDM), which although does not destroy the cells, but helps to monitor the events that leads to initiation of apoptotic cell death. In this study, the apoptogenic property and the cytotoxic effect of P. longifolia leaf methanolic extract (PLME) against the human cervical carcinoma cells (HeLa) was studied using light microscope (LM), holographic digital microscopy (HDM), scanning electron microscope (SEM) and transmission electron microscope (TEM). The average IC 50 value of PLME against HeLa cells obtained by MTT and CyQuant assay was 22.00 μg/mL at 24 h. However, noncancerous Vero cells tested with PLME exhibited no cytotoxicity with the IC 50 value of 51.07 μg/mL at 24 h by using MTT assay. Cytological observations showed nuclear condensation, cell shrinkage, multinucleation, abnormalities of mitochondrial cristae, membrane blebbing, disappearance of microvilli and filopodia, narrowing of lamellipodia, holes, formation of numerous smaller vacuoles, cytoplasmic extrusions and formation of apoptotic bodies as confirmed collectively by HDM, LM, SEM and TEM. In conclusion, PLME was able to produce distinctive morphological features of HeLa cell death that corresponds to apoptosis. [ABSTRACT FROM AUTHOR]

Medicinal plants have been accepted as a gold mine, with respect to the diversity of their phytochemicals. Many medicinal plants extracts are potential anticancer agents. Polyalthia longifolia var. angustifolia Thw. (Annonaceae) is one of the most significant native medicinal plants and is found throughout Malaysia. Hence, the present study was intended to assess the anticancer properties of P. longifolia leaf methanolic extract (PLME) and its underlying mechanisms. The Annexin V/PI flow cytometry analysis showed that PLME induces apoptosis in HeLa cells in dose-dependent manner whereas the PI flow cytometric analysis for cell cycle demonstrated the accumulation of cells at sub G0/G1, G0/G1 and G2/M phases. Investigation with JC-1 flow cytometry analysis indicated increase in mitochondria membrane potential depolarisation corresponding to increase in PLME concentrations. PLME was also shown to influence intracellular reactive oxygen species (ROS) by exerting anti-oxidant (half IC 50 ) and pro-oxidant (IC 50 and double IC 50 ) affect against HeLa cells. PLME treatment also displayed DNA damage in HeLa cells in concentration depended fashion. The proteomic profiling array exposed the expression of pro-apoptotic and anti-apoptotic proteins upon PLME treatment at IC 50 concentration in HeLa cells. Pro-apoptotic proteins; BAX, BAD, cytochrome c, caspase-3, p21, p27 and p53 were found to be significantly up-regulated while anti-apoptotic proteins; BCL-2 and BCL-w were found to be significantly down-regulated. This investigation postulated the role of p53 into mediating apoptosis, cell cycle arrest and mitochondrial potential depolarisation by modulating the redox status of HeLa cells. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Phaleria macrocarpa (Scheff) Boerl, is a well-known folk medicinal plant in Indonesia. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and hearth disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases. Aim of the study The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) and the underlying molecular mechanism of cell death. Materials and methods MDA-MB-231 cells were incubated with PMEAF for 24 h. Cell cycle and viability were examined using flow cytometry analysis. Apoptosis was determined using the Annexin V assay and also by fluorescence microscopy. Apoptosis protein profiling was detected by RayBio® Human Apoptosis Array. Results The AO/PI staining and flow cytometric analysis of MDA-MB-231 cells treated with PMEAF were showed apoptotic cell death. The cell cycle analysis by flow cytometry analysis revealed that the accumulation of PMEAF treated MDA-MB-231 cells in G 0 /G 1 and G 2 /M-phase of the cell cycle. Moreover, the PMEAF exert cytotoxicity by increased the ROS production in MDA-MB-231 cells consistently stimulated the loss of mitochondrial membrane potential (∆ Ψm ) and induced apoptosis cell death by activation of numerous signalling proteins. The results from apoptosis protein profiling array evidenced that PMEAF stimulated the expression of 9 pro-apoptotic proteins (Bax, Bid, caspase 3, caspase 8, cytochrome c , p21, p27, p53 and SMAC) and suppressed the 4 anti-apoptotic proteins (Bcl-2, Bcl-w, XIAP and survivin) in MDA-MB-231 cells. Conclusion The results indicated that PMEAF treatment induced apoptosis in MDA-MB-231 cells through intrinsic mitochondrial related pathway with the participation of pro and anti-apoptotic proteins, caspases, G 0 /G 1 and G 2 /M-phases cell cycle arrest by p53-mediated mechanism. [ABSTRACT FROM AUTHOR]

Amyloid fibrils are associated with different neurodegenerative diseases, a final product of several protein aggregation pathways. Parkinson's disease is a type of amyloidosis, characterized by the accumulation and propagation of amyloid fibrils of alpha-synuclein. The detection of fibrils at low concentrations is critical for the diagnosis of Parkinson's disease. We report a novel technique for the selective detection of amyloid fibrils through a dipole moment on a dielectrode surface. A sensitive dielectrode sensor for detecting aggregation of alpha synuclein and works by interacting an antibody on two-electrode surface functionalized gold interdigitated electrode. For the physical characterization of the sensing surface and finger electrodes, high-power microscope, scanning electron microscope, and 3D-profilormeter were used. Electrical characterization was performed on the sensing surface by using Keithley 6487 picoammeter. Based on the stability analysis with various electrolytes solutions, the sensor was found to be stable from pH 3. Further, under optimal circumstances, a linear range of alpha synuclein fibril detection was from 100 aM to 100 pM [y = 5E-06x + 5E-06; R² = 0.9724], and the limit of detection was estimated to be 100 aM based on S/N = 3. This study was further anchored by molecular docking analysis with synuclein peptide (47−56). We predict that advancements in this direction will assist in clarifying the complex process posed by Parkinson's disease. [Display omitted] • Amyloid fibrils associated with neurodegenerative diseases, in aggregation pathways. • Parkinson's disease is amyloidosis, formed by amyloid fibrils of alpha-synuclein. • Monitored alpha synuclein aggregation on a gold-interdigitated electrode surface. • Detection was at 100 aM, on linear concentrations with coefficient regression. • Anchored by molecular docking with synuclein peptide(47−56), binding region displayed. [ABSTRACT FROM AUTHOR]

Aptamers are single-stranded oligonucleotides that can be artificially generated by a method called Systematic evolution of ligands by exponential enrichment (SELEX). The generated aptamers have been assessed for high-performance sensing applications due to their appealing characteristics. With either aptamers alone or complementing with antibodies, several high sensitive and portable sensors have been demonstrated for use in ‘point-of-care testing’. Due to their high suitability and flexibility, aptamers are conjugated with nanostructures and utilized in field applications. Moreover, aptamers are more amenable to chemical modifications, making them capable of utilization with most developed sensors. In this overview, we discuss novel, portable, and aptamer-based sensing strategies that are suitable for ‘point-of-care testing’. [ABSTRACT FROM AUTHOR]

Background Autoantibodies or antibodies against self-antigens are produced either during physiological processes to maintain homeostasis or pathological process such as trauma and infection. Infection with parasites including Plasmodium has been shown to generally induce elevated self-antibody (autoantibody) levels. Plasmodium knowlesi is increasingly recognized as one of the most important emerging human malaria in Southeast Asia that can cause severe infection leading to mortality. Autoimmune-like phenomena have been hypothesized to play a role in the protective immune responses in malaria infection. Methods We studied the autoantibody profile from serum of eleven patients diagnosed with P. knowlesi . Autoantigen arrays were used to elucidate the autoantibody repertoire of P. knowlesi infected patients. The patented OGT Discovery Array with 1636 correctly folded antigen was employed. Results Analysis of the patient versus control sera gave us 24 antigens with high reactivity with serum antibodies. Conclusions Understanding the autoantibody profile of malarious patients infected with P. knowlesi would help to further understand the host–parasite interaction, host immune response and disease pathogenesis. These reactive antigens may serve as potential biomarkers for cases of asymptomatic malaria and mild malaria or predictive markers for severe malaria. [ABSTRACT FROM AUTHOR]

• Abdominal aortic aneurysm (AAA) is the vascular disease forming when aorta swells. • Insulin-like Growth Factor 1 (IGF1) is the circulating biomarker for AAA detected. • Improved ELISA through the aminated silica nanoparticle (SiO 2) mediation. • 400pM of IGF1 detected on amine-SiO 2 modified ELISA & 12.5 nM in conventional ELISA. • Detected in the mixture of IGF1 and relevant proteins (IGF2 and IGFBP3). Abdominal aortic aneurysm (AAA) is the vascular disease forming when aorta in the abdomen swells. AAA with the size of 5.5 and above has possibility to rupture and leads a death. Insulin-like Growth Factor 1 (IGF1) is the circulating biomarker for AAA diagnosis, in this study IGF1 was detected by the improved Enzyme linked Immunoassay (ELISA). The conventional ELISA necessitates the improvement due to the lesser sensitivity than modern sensors. Higher biomolecular immobilization is one of the wise ways to enhance the sensitivity. This study was aimed to capture a higher number of IGF1 on ELISA surface through the aminated silica (SiO 2) nanoparticle with the size measured to be 80−100 nm. On the amine-SiO 2 modified surface, Glutaraldehyde (GLU) complexed IGF1 was chemically bonded. It was found that 400 pM of IGF1 detected on amine-SiO 2 modified ELISA, whereas the conventional ELISA without nanoparticle mediation shows the limit of detection as 12.5 nM with ∼30 times lower detection. The selectivity experiment was carried out with the mixture of IGF1 and relevant proteins (IGF2 and IGFBP3), and it was noticed that anti-IGF1 selectively detected IGF1. This nanoparticle-mediated surface immobilization captured a higher rate of antigen on a larger surface created for high-performance detection. [ABSTRACT FROM AUTHOR]

Human papilloma virus (HPV) affects predominantly the genital area, which includes vagina, cervix, penis, vulva scrotum, rectum and anus. Among 100 types of HPV, 14 types are considered to cause the risky cancer. The gene HPV-16 E7 is responsible for the development of cancer with the infected women. Earlier identification of this gene sequence avoids the cancer progression. The targeted HPV-16 E7 sequence was sandwiched by capture and reporter sequences on the carbodiimidazole-modified interdigitated electrode (IDE) surface. Target sequence at 100 f. was paired to the capture sequence immobilized on IDE sensing surface. To this surface, different concentrations of reporter sequence with and without gold rod (GNR) were evaluated. In both cases the detections were attained 1 aM by the reporter sequence pairing and with GNR increments in current were found. This enhancement was found to be 1000 folds, considering the condition was revealed in the absence of reporter. This sandwich detection strategy of capture-target-reporter sequences for HPV-16 detection on the IDE sensing surface helps to diagnose the association of cervical cancer. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Phaleria macrocarpa (Scheff) Boerl, is a famous traditional medicinal plant which exhibited cytotoxicity against various cancerous cells. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and heart disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases. Aim of the study Recent studies have demonstrated a potent anticancer potential of P. macrocarpa , especially against HeLa cell. The objective of this study was to investigate the regulation of miRNAs on MDA-MB-231 treated with P. macrocarpa ethyl acetate fraction (PMEAF). Materials and methods The regulation of miRNAs on MDA-MB-231 cells treated with PMEAF was studied through IIlumina, Hi-Seq. 2000 platform of Next Generation Sequencing (NGS) and various in silico bioinformatics tools. Results The PMEAF treatment against MDA-MB-231 cells identified 10 upregulated and 10 downregulated miRNAs. A set of 606 target genes of 10 upregulated miRNAs and 517 target genes of 10 downregulated miRNAs were predicted based on computational and validated databases by using miRGate DB Query. Meanwhile, results from DAVID Bioinformatics Resources 6.8 specified the functional annotation of the upregulated miRNAs involvement in cancer pathway by suppressing the oncogenes and downregulating miRNAs by expressing the tumour suppressor genes in the regulation of apoptosis pathway. Conclusion In conclusion, the results of this study proved that PMEAF is a promising anticancer agent with high cytotoxicity against MDA-MB-231 breast cancer cells and it induced apoptotic cell death mechanism through the regulation of miRNAs. PMEAF might be the best candidate for developing more potent anticancer drugs or chemo preventive supplements. [ABSTRACT FROM AUTHOR]

We investigated the gelation characteristics of aiyu jelly derived from the polymeric extract obtained by washing the seeds of Ficus Pumila var. Awkeotsang. The main gel component is low methoxyl pectin, which forms crosslinks with divalent ions that bind the exuded polysaccharide chains. Unlike many fruit pectins used in jam and jellies that require heating, additional sugars, and acidic conditions to gel, the aiyu exudate gels at room temperature with just the addition of water. In this study, the time-resolved dynamics of the gelation process and the evolution of the viscoelastic relaxation spectrum with frequency and gel age are obtained via Optimally Windowed Chirp rheometry (OWCh), conventional time-sweep rheometry, and cryo-scanning electron microscope (cryo-SEM) microstructural characterization. During gelation, we observed distinctive frequency-dependent inflection points in both the time-evolving storage and loss moduli which occur nearly simultaneously in time. Close inspection of high resolution cryo-SEM images taken at different times during the gelation process showed that the gels initially form nano-fiber networks with mesh sizes on the order of tens of microns and the stiffer mature gels observed at longer times develop sub-micron mesh sizes. These observations suggest a progressive transformation between microstructures may accompany the progressive growth in the elasticity of the aiyu gels and the local inflection points in the viscoelastic moduli. We also developed a multi-species reaction kinetics model for calcium – pectin binding in aiyu gelation. By including methylesterase enzymatic conversion of pectin binding sites, combined with calcium binding and the slower formation of consecutively-bound junction zones, the distinctive inflection points in the viscoelastic moduli are captured by the kinetic gelation model. By combining rheological measurements, microstructural observations, and reaction kinetics modeling, this study not only characterizes a unique water-soluble natural extract that gels at room temperature with no additives or thermomechanical processing, it also demonstrates that the aiyu polysaccharide system is a safe and controllable model for gelation systems in which binding site activation is concurrently coupled to crosslink formation. [Display omitted] • Aqueous aiyu extract gels at room temperature and probed with rheometry, cryo-SEM, and reaction kinetics modeling. • The rise of viscoelasticity during gelation exhibits frequency-dependent inflection points in the viscoelastic moduli. • Cooperation between binding site activation and calcium binding result in progressive network microstructural evolution. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Vascular occlusion is not an uncommon event in malignancy. However, the frequency of ischemic stroke after chemotherapy has been mentioned only occasionally in clinical studies. A large-scale study is lacking. Methods: A retrospective study was conducted at Chang Gung Memorial Hospital, Kaohsiung, Taiwan, to analyze the incidence of ischemic stroke post-chemotherapy, further, to evaluate a possible causative relationship between the ischemic stroke and the chemotherapy regimen, the interval between the latest chemotherapy session and onset of ischemic stroke and the survival of patients with ischemic stroke post-chemotherapy. The data were retrieved from the Cancer Database from 1993 to 2004. Results: During this period, a total of 10,963 patients, with malignancies were followed-up for 1 month after chemotherapy, underwent 45,294 chemotherapy sessions. Among this group, there were 15 patients experiencing 16 ischemic strokes within the first month after the latest chemotherapy. Among them, 14 patients were followed-up until death and one patient was lost in follow-up after discharge against medical advice. The incidence of post-chemotherapy ischemic stroke was 0.137% and the frequency of chemotherapy cycles complicated by ischemic stroke was 0.035%. Adenocarcinoma was the most common histological type not only in ischemic stroke (40%) but also in overall patients (36.7%). The hemispheric stroke with middle cerebral artery territory involvement was the most common image finding. Platinum compounds, especially cisplatin, were the most commonly used chemotherapeutic agents for ischemic stroke patients. Twelve (75%) of these 16 ischemic strokes occurred within 10 days of the latest chemotherapy session and 10 (62.5%) occurred after the first cycle of chemotherapy. The median survival after ischemic stroke was 4 weeks. Conclusion: Our results provide valuable data on the relationship between malignancy, treated with chemotherapy, and ischemic stroke. The risk of ischemic stroke after chemotherapy is predicted by the use of cisplatin-based chemotherapy not cancer histologic type. Infarction usually involves the territorial subtype, causes obvious neurological disabilities and carries a grave prognosis. [Copyright &y& Elsevier]

Highly sensitive and easy detection method for Alzheimer's disease (AD) with a suitable biomarker is mandatory for preventing the factors resulting from AD. This research reports a modified ELISA with graphene for the detection of AD biomarker amyloid beta (Aβ) oligomer. Gold nanoparticle (AuNP) conjugated aptamer was used as the capture probe and attached on ELISA-graphene oxide surface through the amine linker. Antibody was used as the detection molecule to reach the maximum detection of Aβ oligomer. Suitable level of APTMS (2%), size of AuNP (30 nm) and aptamer concentration (2 μM) were optimized. This sandwich pattern of aptamer-Aβ oligomer-antibody helps to reach the detection at 50 pM on the optimized ELISA surface and the control experiments in the absence of Aβ oligomer or anti-Aβ oligomer antibody did not show the significant optical detection at 492 nm, indicting the specific detection. Further, Aβ oligomer spiked artificial cerebrospinal fluid did not interfere the detection of Aβ oligomer, confirming the selective detection. This new and modified ELISA surface helps to reach the lower detection of Aβ oligomer and diagnose AD. [ABSTRACT FROM AUTHOR]