Synergistic modulation of proinflammatory mediators and cytokines in lipopolysaccharide-activated RAW 264.7 macrophages: The therapeutic potential of Elephantopus scaber and Sauropus androgynus ethanol extract.

Background and Aim: Elephantopus scaber (ES) and Sauropus androgynus (SA) have broad biological effects and have long been used in traditional medicine. However, the anti-inflammatory properties of the combination of ES and SA have not yet been fully explored. This study aimed to investigate the anti-inflammatory activities of the combination of ES and SA ethanol extract on lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cell lines by inhibiting proinflammatory mediators and cytokines. Materials and Methods: Nitric oxide (NO) production in RAW 264.7 cells was assessed using the Griess protocol. The effects of the combination of ES and SA ethanol extract on RAW 264.7 cell viability were determined using WST-1 (4-[3-(4-Iodophenyl)-2-(4-nitro-phenyl)-2H-5-tetrazolio]-1,3-benzene sulfonate) assay. The levels of proinflammatory cytokines, including interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-ß), as well as the production of inducible nitric oxide synthase (iNOS), were assessed using flow cytometry. Results: This study demonstrated that ES and SA have excellent NO, iNOS, and proinflammatory inhibitory activities on LPS-induced RAW 264.7 macrophages. The formula ratio of 2ES:1SA showed the best NO inhibitory activity without any cytotoxicity, whereas the higher dose of SA (1ES:2SA) showed the best suppression of iNOS and proinflammatory cytokines IL-1ß, IFN-γ, and TNF-α. Conclusion: The combination of ES and SA ethanol extract could be an alternative agent for reducing excessive inflammation in inflammatory diseases.

Effect of type and concentration of antioxidant on sperm motility, viability, and DNA integrity of climbing perch Anabas testudineus Bloch, 1792 (Pisces: Anabantidae) post-cryopreservation.

Sperm quality is preserved through the crucial involvement of antioxidants, which play a vital role in minimizing the occurrence of reactive oxygen species (ROS) during the cryopreservation process. The suitability of the type and concentration of antioxidants are species-dependent, and this study is crucial in order to improve the quality of the climbing perch sperm post-cryopreservation. Therefore, this study aimed to determine the best type and concentration of antioxidants for cryopreservation of climbing perch Anabas testudineus sperm. To achieve this, 6 types of antioxidants, namely, ascorbic acid, beta-carotene, glutathione, butylated hydroxytoluene (BHT), myo-inositol, and alpha-tocopherol, with inclusion of a control were tested in 3 replications at three concentration levels of 0 mg/L (control), 20 mg/L, 40 mg/L, and 60 mg/L. Sperm was diluted in a glucose-base extender at a ratio of 1:60 (sperm: glucose base), then 10 % DMSO and 5 % egg yolk was added before cryopreservation for two weeks. The results showed that the type and concentration of antioxidants had a significant effect on the motility and viability of cryopreserved climbing perch sperm (P < 0.05), where the best results for ascorbic acid, beta-carotene, glutathione, myo-inositol, and alpha-tocopherol were obtained at a concentration of 60 mg/L, while BHT was at a concentration of 20 mg/L. The best results for glutathione, myo-inositol, and alpha-tocopherol were significantly different from other treatments, while the best results for ascorbic acid and beta-carotene (60 mg/L) were not significantly different from the 40 mg/L concentration, while the best results for BHT were not significantly different from the control treatments. Therefore, the best concentration of glutathione, myo-inositol, and alpha-tocopherol was 60 mg/L, while for ascorbic acid and beta-carotene it was 40 mg/L, and BHT was not recommended. DNA integrity analysis indicated the absence of fragmentation in all samples, including fresh, control, and treated sperm. Based on practical and economic considerations, myo-inositol at 60 mg/L was recommended for cryopreservation of climbing perch A. testudineus sperm.

Review: The role of heat shock proteins in chicken: Insights into stress adaptation and health.

This review article aimed to provide readers with a comprehensive understanding of the function of heat shock proteins (HSPs) in chicken physiology, stress response, and overall poultry health. With the increasing challenges faced by the livestock industry, particularly the poultry sector, due to climate change-induced high ambient temperatures, heat stress (HS) has become a critical concern. HS disrupts the thermal balance in poultry, leading to detrimental effects on growth, immune function, and overall health. HSPs play a pivotal role in mitigating the impacts of HS in chickens. These molecular chaperones are involved in protein folding, unfolding, and assembly, and they are classified into several families based on their size, including small molecule HSPs, HSP40, HSP60, HSP70, HSP90, and HSP110. By maintaining cellular homeostasis and promoting stress tolerance, HSPs act as vital guardians in helping chickens cope with HS and its associated consequences. The review synthesized relevant literature to shed light on the importance of HSPs in stress adaptation, cellular homeostasis, and the maintenance of normal cell metabolism in chickens. The adverse effects of HS on chickens include oxidative stress and compromised immune systems, making them more susceptible to infections. So also, HS negatively affects production performance and meat quality in poultry. Understanding the functions of HSPs in chickens offers valuable insights into stress adaptation and health, and could potentially lead to the identification of HSP biomarkers, genetic selection for heat tolerance, investigations into the interplay between HSPs and immune function, and the development of nutritional interventions to enhance HSP activity. By exploring these potential research directions, the review aimed to contribute to the development of novel approaches to mitigate the negative effects of HS on poultry, ultimately improving productivity and animal welfare in a changing climate.

Effect of modified CEP-3 diluents with aqueous soybean extract on liquid semen quality in Ongole crossbred bull.

Background and Aim: Egg yolk (EY) is commonly used as an extracellular cryoprotectant in semen diluents but has some negative effects. Therefore, this study aimed to assess the potential of lecithin derived from plants, such as soybeans, as an alternative extracellular cryoprotectant and to characterize liquid semen quality of Ongole crossbred bulls using a modified caudal epididymis plasma-3 [CEP-3 (m)] as a base diluent and aqueous soybean extract (ASE). Materials and Methods: A bull with progressive motility (PM) of fresh semen >70% was used. Two soybean extracts were also used, namely, ASE 1 and ASE 2, obtained by extraction procedures 1 and 2, respectively. The study was conducted using an experimental design with 11 treatments and ten replications, with diluents comprising different levels of ASE 1 and ASE 2, as well as a positive control with 10% EY. The parameters measured were motility (M) and its kinetic parameters, including PM, M, velocity curve linear, velocity straight linear, velocity average pathway, linearity, straightness, wobble, amplitude lateral head beat cross frequency, and hyperactivity using computer-assisted sperm analysis, viability, and spermatozoa abnormalities. Results: The CEP-3(m) diluent formula and ASE 1 at a 30% level maintained the PM of spermatozoa up to day 5 (40.7% ± 16.1%) of cold storage. Meanwhile, the CEP-3(m) diluent formula and ASE 2 could only maintain PM >40% until day 3 (42.1% ± 13.5%) of cold storage at a 30% level. The CEP-3(m) diluent and ASE 1 at a level of 25%-30% supported spermatozoa life (viability) up to day 5 with a value >80% (81.8 ± 3.5; 86.4 ± 2.6). The abnormality value of spermatozoa in various diluents during cold storage on days 0-5 was below 20%. Conclusion: Soybean extracts 1 and 2 can substitute EYs as extracellular cryoprotectants in modified CEP-3 basic diluents. Soybean extract 1 can support the life of spermatozoa up to day 5 but may cause the viscosity and movement of spermatozoa to be hyperactive. Soybean extract 2 can support the life of spermatozoa up to the 3rd day of cold storage and produces progressive (non-rotating) movement patterns. Further, research is recommended with higher levels of ASE 2.

Computational evaluation of bioactive compounds in Curcuma zanthorrhiza targeting SIRT1 and NFκB.

Type 2 diabetes mellitus (T2DM) is a metabolic disease with a high risk of complications and mortality. Novel T2DM therapeutic interventions are needed to combat this disease. This study aimed to identify pathways involved in T2DM and investigate sesquiterpenoid compounds from Curcuma zanthorrhiza that could act as SIRT1 activators and NFκB inhibitors. Protein-protein interaction and bioactive compound analysis were conducted using the STRING and STITCH databases, respectively. Molecular docking was used to determine the compounds' interactions with SIRT1 and NFκB, while toxicity prediction was performed using Protox II. The results showed that curcumin could act as a SIRT1 activator (4I5I, 4ZZJ, and 5BTR) and NFκB inhibitor on the p52 relB complex and p50-p65 heterodimer, while xanthorrhizol could function as an IκK inhibitor. The toxicity prediction indicated that the active compounds of C. zanthorrhiza were relatively nontoxic because beta-curcumene, curcumin, and xanthorrizol belong to toxicity classes 4 or 5. These findings suggest that the bioactive compounds of C. zanthorrhiza could be promising candidates for developing SIRT1 activators and NFκB inhibitors to combat T2DM.

Investigation renin inhibitor activity from flavonoids derivates by in silico study.

Flavonoids have various pharmacological activities, such as antihypertensive, anticancer, and and antidiabetic effects. Several studies have shown that luteolin, quercetin, kaempferol, myricetin, naringenin, hesperetin, and epicatechin have antihypertensive effects, but the mechanism of action has yet to be discovered with certainty. This study aims to identify flavonoids from luteolin, quercetin, kaempferol, myricetin, naringenin, hesperetin, and epicatechin as renin inhibitors through in silico study; seven flavonoid compounds were docked with 2V0Z with renin inhibitor (Aliskiren) in humans (Homo sapiens 6 LU7) using AutoDock v4.2.6. SwissADME was used to evaluate the pharmacokinetic characteristics of these substances. Results molecular binding of luteolin, quercetin, kaempferol, myricetin, naringenin, hesperetin, and epicatechin, has potential as renin inhibitors with affinity energy values lower than those of aliskiren of -9.3; -9.3; -10.0; -9.2; -9.9; -9.3; and -9.7 kcal/mol. The interactions of these seven compounds have the same catalytic activity as aliskiren on two aspartic acid residues, Asp32 and Asp215. The analysis of pharmacokinetic profiles and the search for physical and chemical properties showed that the seven compounds violated three of the five Lipinski rules, while aliskiren violated one. Hesperitin, kaempferol, and naringenin had similarities with aliskiren on the amino-acid residues in the renin-binding pocket. However, based on pharmacokinetic analysis, the three compounds had an oral pharmacokinetic profile that could have been better than aliskiren.

Lost to Follow-Up among Tuberculosis Patients during the Public-Private Mix Era in Rural Area of Indonesia.

Background: Indonesia's national Tuberculosis (TB) strategy is public-private mix (PPM). The PPM aims to treat patients who have lost sight during TB treatment as these patients are TB carriers and at risk of transmitting TB. The purpose of this study was to identify predictive factors for loss to follow-up (LFTU) among TB patients receiving treatment when the PPM was at place in Indonesia. Methods: The design of this study was a retrospective cohort study. The data used in this study was sourced from the Tuberculosis Information System (SITB) of Semarang which was recorded routinely during 2020-2021. Univariate analysis, crosstabulation, and logistic regression were performed on 3434 TB patients meeting the minimum variables. Results: The participation of health facilities in reporting TB during the PPM era in Semarang reached 97.6% consisting of 37 primary healthcare center (100%), 8 public hospitals (100%), 19 private hospitals (90.5%), and a community-based pulmonary health center (100%). The regression analysis reveal that the predictive factors of LTFU-TB during the PPM are the year of diagnosis (AOR=1.541; p-value=<0.001; 95% CI=1.228-1.934), referral status (AOR=1.562, p-value=0.007; 95% CI=1.130-2160), healthcare and social security insurance ownership (AOR=1.638; p-value=<0.001; 95% CI=1.263-2.124), drugs source (AOR=4.667; p-value=0.035; 95% CI=1.117-19.489). Conclusions: The PPM strategy in dealing with LTFU patients should focus on TB patients without Healthcare and Social Security Insurance and who receive TB treatment rather than program drugs.

Hepatic Transcriptome Analysis Reveals Genes, Polymorphisms, and Molecules Related to Lamb Tenderness.

Tenderness is a key meat quality trait that determines the public acceptance of lamb consumption, so genetic improvement toward lamb with higher tenderness is pivotal for a sustainable sheep industry. However, unravelling the genomics controlling the tenderness is the first step. Therefore, this study aimed to identify the transcriptome signatures and polymorphisms related to divergent lamb tenderness using RNA deep sequencing. Since the molecules and enzymes that control muscle growth and tenderness are metabolized and synthesized in the liver, hepatic tissues of ten sheep with divergent phenotypes: five high- and five low-lamb tenderness samples were applied for deep sequencing. Sequence analysis identified the number of reads ranged from 21.37 to 25.37 million bases with a mean value of 22.90 million bases. In total, 328 genes are detected as differentially expressed (DEGs) including 110 and 218 genes that were up- and down-regulated, respectively. Pathway analysis showed steroid hormone biosynthesis as the dominant pathway behind the lamb tenderness. Gene expression analysis identified the top high (such as TP53INP1, CYP2E1, HSD17B13, ADH1C, and LPIN1) and low (such as ANGPTL2, IGFBP7, FABP5, OLFML3, and THOC5) expressed candidate genes. Polymorphism and association analysis revealed that mutation in OLFML3, ANGPTL2, and THOC5 genes could be potential candidate markers for tenderness in sheep. The genes and pathways identified in this study cause variation in tenderness, thus could be potential genetic markers to improve meat quality in sheep. However, further validation is needed to confirm the effect of these markers in different sheep populations so that these could be used in a selection program for lamb with high tenderness.

Development of blood hemoglobin level early detection device based on a noninvasive optical platform.

Blood hemoglobin levels are a reliable indicator for anemia screening, which generally uses an invasive system or takes blood using a syringe. Spectrophotometry can work by "substituting" the use of a phlebotomy tube needle with electromagnetic wave radiation or light. This study aims to develop and carry out a noninvasive diagnostic test for measuring hemoglobin levels. There are three main stages in this research: (i) measuring hemoglobin concentration and scanning an incident wavelength on standard hemoglobin solutions and blood controls, (ii) making a prototype variant of a noninvasive blood hemoglobin level measurement device, and (iii) testing the technology unit on the developed prototype. The measured hemoglobin value by the Trax Control Meter for low, middle, and high levels is almost the same as the expected range values, namely, 13.09, 16.8, and 17.81 g/dL, respectively. Three sets of device prototype variants were successfully developed: (i) the noninvasive blood hemoglobin level measuring device based on Raspberry Pi Prototype on Infant Finger and Thigh Probes, (ii) the level measuring prototype noninvasive hemoglobin in blood based on Internet of Things and WebServer, and (iii) the prototype of noninvasive blood hemoglobin level measuring device on in vitro probe with reflectance method. Testing the accuracy of the Biorad MeterTrax Trilevel using a multiformula regression calculation using the ZunZun server shows that the tool has an accuracy ranging from 0.12 to 0.30 g/dL.

Development of the SIKRIBO Mobile Health Application for Active Tuberculosis Case Detection in Semarang, Indonesia.

OBJECTIVES: This study was conducted to document the development and usability testing of SIKRIBO, a tuberculosis screening application. METHODS: The SIKRIBO application was developed using design science research methodology, which has six steps: problem identification and motivation, definition of objectives for a solution, product design and development, demonstration, evaluation, and communication. A system usability scale (SUS) questionnaire was used to assess application usability. A total of 20 health cadres (trained community members) and health workers participated in the usability tests. RESULTS: Two versions of the application were developed: Android-based for users and web-based for administrators. The Android-based version has four main menus: Find Tuberculosis, Tuberculosis Education, Latest Info, and Profile. The web version is accessible to health workers, as well as the research team and application developers who monitor and manage the user-conducted screenings. The average SUS score was 76 (standard deviation, 8.00). CONCLUSIONS: This application was developed to help detect active tuberculosis cases in the community. The SUS results indicate that the application is highly usable. Thus, SIKRIBO is expected to be broadly implemented to increase tuberculosis case detection through active community participation.

Flavonoids and phenylethanoids from the flowers and leaves of Aeschynanthus species and cultivars (Gesneriaceae).

Forty-one flavones, each one of flavonol, chalcone and dihydroflavonol, two flavanones, and four phenylethanoids were isolated from corollas, calyces and leaves of two Aeschynanthus species, A. fulgens and A. pulcher, and six cultivars, 'Mahligai', 'Mona Lisa', SoeKa', 'Redona', 'Freshya' and 'Bravera'. Flavonoids were mainly the glucuronides and/or methylglucuronides based on hispidulin, nepetin, pectolinarigenin, 6-hydroxyluteolin, scutellarein, apigenin and luteolin, and identified by UV spectra, HR-MS, LC-MS, acid hydrolysis, NMR, and/or HPLC and TLC comparisons with authentic samples. Of these flavonoids, twelve, i.e. hispidulin 7,4'-di-O-glucuronide, 7,4'-di-O-methylglucuronide, 7-O-methylglucuronide-4'-O-glucuronide, 7-O-glucuronide-4'-O-methylglucuronide, 7-O-glucosyl-(1 â†’ 2)-glucuronide and 8-C-glucoside, nepetin 7,4'-di-O-glucuronide, 7-O-glucuronide-4'-O-methylglucuronide and 7-O-methylglucuronide-4'-O-glucuronide, pectolinarigenin 7-O-glucosyl-(1 â†’ 2)-glucuronide and 7-O-xylosyl-(1 â†’ 2)-(6″-malonylglucoside), and 6-hydroxyluteolin 7,4'-di-O-glucuronide, were previously undescribed.

Prevalence and Determinants of Opportunistic Infections in HIV Patients: A Cross-Sectional Study in the City of Semarang.

Background: Opportunistic infection (OI) is the most significant complication of the human immunodeficiency virus (HIV). Differences in the characteristics of HIV patients make the prevalence of Opportunistic infection different between regions. The study aimed to identify variables associated with OI incidence among HIV-infected patients in Semarang City, Indonesia. Methods: This study uses secondary data sourced from special HIV surveillance for 2019-2021 with a cross-sectional method. 1362 HIV patients with variables health care facilities; year of diagnosis; area of residence; age; sex; pregnancy status; occupation; risk factors; risk group determined based on purposive sampling were included in the chi-square analysis and logistic regression. Results: This study showed 12.3% (n=167) of HIV patients experienced OI, where OI was more common in HIV patients with risk groups of sex workers (28.70%), high-risk partners (18.60%), and Male Sex with Men (MSM) (15.40). The most common types of OI were tuberculosis infection (43%), candidiasis (21%), and diarrhea (9%). Age was the variable most associated with the incidence of OI (p-value 0.001). Conclusions: Age groups 45-54 years and 55-64 years have the most influential association with Opportunistic infection incidence in HIV patients, so planning an appropriate intervention program for this subpopulation is necessary.

Magnetic Graphene-Based Nanosheets with Pluronic F127-Chitosan Biopolymers Encapsulated α-Mangosteen Drugs for Breast Cancer Cells Therapy.

In this study, multifunctional chitosan-pluronic F127 with magnetic reduced graphene oxide (MRGO) nanocomposites were developed through the immobilization of chitosan and an amphiphilic polymer (pluronic F127) onto the MRGO. Physicochemical characterizations and in-vitro cytotoxicity of nanocomposites were investigated through field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, particle size analysis, vibrating sample magnetometer, Raman spectroscopy and resazurin-based in-vitro cytotoxicity assay. FESEM observation shows that the magnetic nanoparticles could tethered on the surface of MRGO, promoting the magnetic properties of the nanocomposites. FTIR identification analysis revealed that the chitosan/pluronic F127 were successfully immobilized on the surface of MRGO. Furthermore, α-mangosteen, as a model of natural drug compound, was successfully encapsulated onto the chitosan/pluronic F127@MRGO nanocomposites. According to in-vitro cytotoxicity assay, α-mangosteen-loaded chitosan/pluronic F127@MRGO nanocomposites could significantly reduce the proliferation of human breast cancer (MFC-7) cells. Eventually, it would be anticipated that the novel α-mangosteen-loaded chitosan/pluronic F127@MRGO nanocomposites could be promoted as a new potential material for magnetically targeting and killing cancer cells.

Association study and expression analysis of olfactomedin like 3 gene related to meat quality, carcass characteristics, retail meat cut, and fatty acid composition in sheep.

OBJECTIVE: The objective of this study was to identify polymorphism in olfactomedin like 3 (OLFML3) gene, and association analysis with meat quality, carcass characteristics, retail meat cut, and fatty acid composition in sheep, and expression quantification of OLFML3 gene in phenotypically divergent sheep. METHODS: A total of 328 rams at the age of 10 to 12 months with an average body weight of 26.13 kg were used. A novel polymorphism was identified using high-throughput sequencing in sheep and genotyping of OLFML3 polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Among 328 rams, 100 rams representing various sheep genotypes were used for association study and proc general linear model was used to analyse association between genotypes and phenotypic traits. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for the expression analysis of OLFML3 mRNA in phenotypically divergent sheep population. RESULTS: The findings revealed a novel polymorphism in the OLFML3 gene (g.90317673 C>T). The OLFML3 gene revealed three genotypes: CC, CT, and TT. The single nucleotide polymorphism (SNP) was found to be significantly (p<0.05) associated with meat quality traits such as tenderness and cooking loss; carcass characteristics such as carcass length; retail meat cut such as pelvic fat in leg, intramuscular fat in loin and tenderloin, muscle in flank and shank; fatty acids composition such as tridecanoic acid (C13:0), palmitoleic acid (C16:1), heptadecanoic acid (C17:0), ginkgolic acid (C17:1), linolenic acid (C18:3n3), arachidic acid (C20:0), eicosenoic acid (C20:1), arachidonic acid (C20:4n6), heneicosylic acid (C21:0), and nervonic acid (C24:1). The TT genotype was associated with higher level of meat quality, carcass characteristics, retail meat cut, and some fatty acids composition. However, the mRNA expression analysis was not different among genotypes. CONCLUSION: The OLFML3 gene could be a potential putative candidate for selecting higher quality sheep meat, carcass characteristics, retail meat cuts, and fatty acid composition in sheep.

DNA Barcoding Medicinal Plant Species from Indonesia.

Over the past decade, plant DNA barcoding has emerged as a scientific breakthrough and is often used to help with species identification or as a taxonomical tool. DNA barcoding is very important in medicinal plant use, not only for identification purposes but also for the authentication of medicinal products. Here, a total of 61 Indonesian medicinal plant species from 30 families and a pair of ITS2, matK, rbcL, and trnL primers were used for a DNA barcoding study consisting of molecular and sequence analyses. This study aimed to analyze how the four identified DNA barcoding regions (ITS2, matK, rbcL, and trnL) aid identification and conservation and to investigate their effectiveness for DNA barcoding for the studied species. This study resulted in 212 DNA barcoding sequences and identified new ones for the studied medicinal plant species. Though there is no ideal or perfect region for DNA barcoding of the target species, we recommend matK as the main region for Indonesian medicinal plant identification, with ITS2 and rbcL as alternative or complementary regions. These findings will be useful for forensic studies that support the conservation of medicinal plants and their national and global use.

Health Personnel Improvement in the Implementation of Shariah's Ethical Code of Conduct in Tangerang Hospital, Indonesia.

Background: The Shariah hospital aims to provide health services inclusive of the appropriate code of ethics of Sharia, which exceeds the standard of service expected of conservative hospitals. Hospital care depends on the performance of health professionals. The study aimed to assess the relationship between the implementation of the ethical code of Shariah hospitals and the performance of health personnel. Methods: The study is a quantitative analysis that collects cross-sectional data from 119 health personnel respondents in one Shariah hospital in Indonesia. Data analysis was performed using structural equation modeling (SEM). Results: The implementation of the ethical code of Shariah hospitals, whether explicit or implicit, has a significantly positive influence on the performance and well-being of health personnel, which is evident from the t value of 4.31 (more substantial than the t value of 1.960). This implementation should run consistently and with the commitment of all parties. Conclusion: Such insight, in turn, can be counted as an input to an approach to health services, particularly in increasing the performance rates in hospital. This study is the first to provide new insight into discussion about Shariah hospital's code of conduct by presenting its beneficiary to not only improve health personnels' performance but also provide the inclusive health service for all religions and cultures which is essential in further study.

Preclinical Therapeutic Assessment of a New Chemotherapeutics [Dichloro(4,4'-Bis(2,2,3,3-Tetrafluoropropoxy) Methyl)-2,2'-Bipryridine) Platinum] in an Orthotopic Patient-Derived Xenograft Model of Triple-Negative Breast Cancers.

Cisplatin is one of the most common therapeutics used in treatments of several types of cancers. To enhance cisplatin lipophilicity and reduce resistance and side effects, a polyfluorinated bipyridine-modified cisplatin analogue, dichloro[4,4'-bis(2,2,3,3-tetrafluoropropoxy)methyl)-2,2'-bipryridine] platinum (TFBPC), was synthesized and therapeutic assessments were performed. TFBPC displayed superior effects in inhibiting the proliferation of several cisplatin-resistant human cancer cell lines, including MDA-MB-231 breast cancers, COLO205 colon cancers and SK-OV-3 ovarian cancers. TFBPC bound to DNA and formed DNA crosslinks that resulted in DNA degradation, triggering the cell death program through the PARP/Bax/Bcl-2 apoptosis and LC3-related autophagy pathway. Moreover, TFBPC significantly inhibited tumor growth in both animal models which include a cell line-derived xenograft model (CDX) of cisplatin-resistant MDA-MB-231, and a patient-derived xenograft (PDX) model of triple-negative breast cancers (TNBCs). Furthermore, the biopsy specimen from TFBPC-treated xenografts revealed decreased expressions of P53, Ki-67 and PD-L1 coupled with higher expression of cleaved caspase 3, suggesting TFBPC treatment was effective and resulted in good prognostic indications. No significant pathological changes were observed in hematological and biochemistry tests in blood and histological examinations from the specimen of major organs. Therefore, TFBPC is a potential candidate for treatments of patients suffering from TNBCs as well as other cisplatin-resistant cancers.

Improving Tirapazamine (TPZ) to Target and Eradicate Hypoxia Tumors by Gold Nanoparticle Carriers.

Tumor hypoxia is a hallmark of solid tumors and emerged as the therapeutic target for cancer treatments, such as a prodrug Tirapazamine (TPZ) activated in hypoxia. To increase tumor accumulation, gold nanoparticles (GNPs) were selected to conjugate with TPZ. In this study, we successfully formulated and assessed the biochemical and therapeutic roles of the conjugated gold nanoparticles-Tirapazamine (GNPs-TPZ) on therapeutic assessments of MKN45-induced xenograft animal model. The results indicated that GNPs-TPZ was a potential nanomedicine for selectively targeting hypoxia tumors coupled with decreased side effects on healthy tissue or organs. TPZ significantly reduced cell viability of hypoxic gastric cancer MKN45 cells, but not in cells incubated in normoxia condition. For improving tumor targeting efficiency, furthermore, the GNPs drug carrier was conjugated to TPZ via biding mediator bovine serum albumin (BSA), and we demonstrated that this conjugated GNPs-TPZ retained the unique characteristics of hypoxic toxin and possessed the adequate feature of systemic bio-distributions in animals. GNPs-TPZ nanoparticles revealed their superior affinity to hypoxia tumors in the MKN45 xenograft. Moreover, GNPs-TPZ treatments did not significantly alter the biochemical parameters of blood samples acquired from animals. Taken together, TPZ, a prodrug activated by hypoxia, was conjugated with GNPs, whereas BSA severed as an excellent binding agent for preparing the conjugated GNPs-TPZ nanomedicines. We demonstrated that GNPs-TPZ enhanced tumor targeting, resulting in higher therapeutic efficacy compared to TPZ. We suggest that it may sever as an adjuvant treatment or combined therapy with other chemotherapeutics for the treatment of cancer patients in the future.

The National Health Insurance System of Indonesia and primary care physicians' job satisfaction: a prospective qualitative study.

BACKGROUND: The implementation of the National Health Insurance System (NHIS) in Indonesia has been changing the primary care physician (PCP) work condition and their job satisfaction. OBJECTIVE: This research aimed to explore the reasons behind PCPs' satisfaction and dissatisfaction with job satisfaction's aspect under the NHIS reform. METHODS: We conducted an exploratory qualitative study within two areas in Central Java, Indonesia, using semi-structured in-depth interviews with 34 PCPs and 19 triangulation sources. We conducted both inductive and deductive analyses by the NVivo 11. RESULTS: Most PCPs felt dissatisfied with the following aspects of the NHIS: referral system, NHIS health services standard, NHIS programmes, performance evaluation and pay-for-performance, relationship with patient and workloads. PCPs felt constrained with the referral regulation and non-specialist diagnoses, which led to dissatisfaction with performance evaluation and the pay-for-performance implementation. Furthermore, an increase in workload and conflict with patients resulted from patients' misunderstanding the NHIS health service procedures. However, PCPs felt satisfied with the chronic disease management programme and patients' appreciation. CONCLUSIONS: This study presents the reasons behind PCPs' satisfaction and dissatisfaction with job satisfaction's aspect under the NHIS reform. There is a need for additional discussion among all stakeholders (Ministry of Health, Social Security Agency for Health/SSAH, primary health care and physician's professional organizations about the non-specialist diagnoses list, performance evaluation and pay-for-performance). The government and SSAH need to improve the communication and socialization of the NHIS procedures/regulations.

In 2014, Indonesia implemented a National Health Insurance System (NHIS). The reform affected the primary care physicians' (PCPs') work conditions and job satisfaction. This qualitative study explored the reasons behind PCPs' satisfaction and dissatisfaction with the job satisfactions' aspect in the NHIS. We interviewed 34 PCPs and 19 triangulation sources in Semarang City and Demak Regency (Central Java). Findings showed that most physicians felt dissatisfied with the NHIS referral system, health services standard, some NHIS programmes, performance evaluation and pay-for-performance, relationship with patients and workload. Mostly, the patients­PCPs' conflicts were due to the misunderstanding of the NHIS health service procedures. However, the PCPs also received patients' appreciation. For improving the reform implementation and PCPs' job satisfaction, the physicians' concerned, leading to dissatisfaction, must be addressed.

Acylated pelargonidin and cyanidin 3-sambubiosides from the flowers of Aeschynanthus species and cultivars.

Thirteen anthocyanins were isolated from the flowers of two Aeschynanthus species, A. fulgens and A. pulcher, and six cultivars, 'Mahligai', 'Mona Lisa', 'SoeKa', 'Redona', 'Freshya' and 'Bravera', and identified as pelargonidin and cyanidin 3-O-sambubiosides and their malonates, succinates, p-coumarates and caffeates, and pelargonidin 3-O-glucoside by acid hydrolysis, HR-MS and NMR. Of their anthocyanins, pelargonidin 3-O-[xylosyl-(1 â†’ 2)-(6''-malonylglucoside)] (2), pelargonidin 3-O-[xylosyl-(1 â†’ 2)-(6''-succinylglucoside)] (3), pelargonidin 3-O-[xylosyl-(1 â†’ 2)-(6''-E-p-coumaroylglucoside)] (4), pelargonidin 3-O-[xylosyl-(1 â†’ 2)-(6''-Z-p-coumaroylglucoside)] (5), pelargonidin 3-O-[xylosyl-(1 â†’ 2)-(6''-E-caffeoylglucoside)] (6) and cyanidin 3-O-[xylosyl-(1 â†’ 2)-(6''-succinylglucoside)] (9) were reported in nature for the first time.