Synthesis And Evaluation Of Cross-Linked Disulphide Containing Polymers For Colonic Drug Delivery

Kolon telah dilaporkan sebagai tapak sasaran yang sesuai bagi penyerapan sistemik protein dan peptida terapeutik drug kerana aktiviti peptidase yang lebih rendah, meghampiri pH neutral dan keadaan ‘perbalahan’ yang kurang jika dibandingkan dengan kawasan lain daripada saluran pencernaan. Bentuk dosaj yang diformulasikan mesti melalui saluran pencernaan bahagian atas dalam bentuk utuh sebelum penghantaran drug kepada kolon. Penggunaan polimer disulfida sebagai satu penghantaran responsif bakteria merupakan salah satu strategi untuk menyasarkan drug kepada kolon bagi melepaskan drug secara khusus dalam kolon. Colon has been reported as a favourable target site for the systemic absorption of therapeutic protein and peptide drugs, because of its lower peptidase activity, near neutral pH and less hostile conditions as compared with other regions of gastrointestinal tract. The formulated dosage form must pass through the upper gastrointestinal tract in intact form before delivering the drug to the colon. The use of disulphide polymers, a bacteria responsive delivery, is one of the strategies for targeting drugs to the colon and to release drug specifically in the colon

Pharmacognostic and Antioxidant Properties of Dracaena sanderiana Leaves

Endogenous and exogenous antioxidants are used to neutralise free radicals and protect the body from free radicals by maintaining the redox balance. The antioxidant properties of Dracaena sanderiana leaves were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and the total phenolic and flavonoid contents were measured. The classes of secondary metabolites were evaluated through pharmacognostic studies, and active compounds were identified by gas chromatography mass-spectrometry (GC-MS). All ethanol-water extracts and D. sanderiana leaf powder were positive for tannins, saponins, terpenoids, cardiac glycosides, and quinones. Flavonoids were present in 100%, 80%, 60%, and 40% ethanol extracts (E100, E80, E60, and E40). E100 showed the highest total flavonoid content, whereas E60 extract showed the highest antioxidant activity and total phenolic content. GC-MS revealed the presence of glycerol, 2,3-dihydro-3,5-dihydroxy-6-methyl-(4H)-pyran-4-one, n-dodecanoic acid, tetradecanoid acid, (n-) hexadecanoid acid, and n-octadecanoic acid in the E60 extract

ASSESSMENT OF PLATELET CONCENTRATE PREPARED FROM FRESH AND OVERNIGHT HELD WHOLE BLOOD

Separation of platelet rich plasma (PRP) within 8 hours after holding whole blood at ambient temperature is the current practice in the preparation of platelet concentrate (PC). However, the ability to hold whole blood for up to 24 hours prior to PC preparation would allow every unit of whole blood to be used regardless of the distance from the collection site to the processing centre. Therefore the aim of this study is to assess and compare the platelet quality and activation of the platelet concentrate prepared from fresh whole blood (within 8 hours from collection) and overnight hold of whole blood at room temperature. In this study, 23 units of PC were prepared freshly from whole blood (i.e., within 8 hours of collection) and another 23 units were prepared after 24 hours of storage at 20–24 ºC. The following parameters of each unit of PC were assessed: pH, total white blood cell (TWBC) count, platelet count, presence of swirling, and platelet activation. When the parameters were compared between groups, no significant difference in platelet activation rate was found on sampling days 1, 3, and 5. pH and TWBC count for both groups were within the quality requirements of the National Blood Centre (> 75% units tested fall within the standard), but not all of the samples complied with the standard requirement for platelet count. All units of PC prepared after 24 hours showed the presence of swirling, whereas one unit of PC in the fresh group did not show swirling activity after 3 days of storage. Delaying whole blood processing for up to 24 hours does not significantly affect certain in vitro quality or activation parameters as compared with freshly prepared PC. Â

In vitro analysis of quercetin-like compounds from mistletoe Dendrophthoe pentandra (L.) Miq as a potential antiviral agent for Newcastle disease [version 5; peer review: 1 approved, 2 approved with reservations]

Background Recent evidence suggests that some flavonoid compounds obtained from crude methanol extract of mistletoe leaves (Dendrophthoe pentandra L. Miq), also known as Benalu Duku (BD), have antimicrobial effects. Thus, the plant has the potential to eliminate viruses that may cause outbreaks in chicken farms. This study aimed to prove the in vitro ability of flavonoid compounds, namely quercetin-like compounds (QLCs), to eliminate field viruses, specifically the Newcastle disease virus (NDV). Methods This research was performed in two stages. An in vitro test was used with a post-test of the control groups designed at a significance of 0.05. BD leaves (5 kg) were extracted using a maceration method with methanol and then separated into hexane, chloroform, ethyl acetate, and methanol fractions. The final extracted products were separated using semi-preparative high-performance liquid chromatography (HPLC) to obtain QLCs. The QLCs were identified and compared with quercetin using HPLC, proton and carbon nuclear magnetic resonance spectrometry, Fourier transform infrared spectrophotometry, and ultra-performance liquid chromatography–mass spectrometry. The activity of QLCs was tested in vitro against the NDV at a virulence titer of 10−5 Tissue Culture Infectious Dose 50% (TCID50) in chicken kidney cell culture. Results Solutions of 0.05% (w/v) QLCs were discovered to have antiviral activity against NDVs, with an average cytopathogenic effect antigenicity at a 10−5 dilution (p<0.05). Conclusions QLCs from flavonoids from the leaves of BD have in vitro antiviral bioactivity against NDV at a virulence titer of 10-5 Tissue Culture Infectious Dose 50% (TCID50) in chicken kidney cell culture. QLCs may have the potential to be developed as medicinal compounds for the treatment of other human or animal viral infections

Anti-cancer effects of Vernonia amygdalina: A systematic review

Purpose: To systematically review all the studies that have addressed the anti-cancer activities of the VA leaf extract in vitro to determine the strength of evidence of its anti-cancer effects and whether it can be used as an effective cancer therapy.Methods: The databases of Scopus, Science Direct, PubMed, Springer, and Directory of Open Access Journals were searched for relevant articles. Only articles published in the English language from January 2000 to November 2018 were selected for full-text retrieval and review, before being included in the final review.Results: From a total of 28 articles identified for full-text retrieval, only 17 fulfilled the inclusion criteria. The papers reviewed showed that VA decreases cell viability, inhibits DNA synthesis and causes DNA damage in cancer cells. VA also induces apoptosis and cell cycle arrest in cancer cells via gene regulation. All in all, there is evidence showing that VA possesses time- and concentration-dependent anti-cancer activity.Conclusion: The VA leaf extract has the potential to be developed into cancer therapeutics. However, more research is needed on its effect on normal cells before VA is developed into a cancer therapeutic. Keywords: Vernonia amygdalina, Anti-cancer effect, DNA damage, Apoptosi

In vitro analysis of quercetin-like compounds from mistletoe Dendrophthoe pentandra (L.) Miq as a potential antiviral agent for Newcastle disease [version 6; peer review: 1 approved, 2 approved with reservations]

Background Recent evidence suggests that some flavonoid compounds obtained from crude methanol extract of mistletoe leaves (Dendrophthoe pentandra L. Miq), also known as Benalu Duku (BD), have antimicrobial effects. Thus, the plant has the potential to eliminate viruses that may cause outbreaks in chicken farms. This study aimed to prove the in vitro ability of flavonoid compounds, namely quercetin-like compounds (QLCs), to eliminate field viruses, specifically the Newcastle disease virus (NDV). Methods This research was performed in two stages. An in vitro test was used with a post-test of the control groups designed at a significance of 0.05. BD leaves (5 kg) were extracted using a maceration method with methanol and then separated into hexane, chloroform, ethyl acetate, and methanol fractions. The final extracted products were separated using semi-preparative high-performance liquid chromatography (HPLC) to obtain QLCs. The QLCs were identified and compared with quercetin using HPLC, proton and carbon nuclear magnetic resonance spectrometry, Fourier transform infrared spectrophotometry and ultra-performance liquid chromatography-mass spectrometry. The activity of QLCs was tested in vitro against the NDV at a virulence titter of 10−5 Tissue Culture Infectious Dose 50% (TCID50) in chicken kidney cell culture. Results Solutions of 0.05% (w/v) QLCs were discovered to have antiviral activity against NDVs, with an average cytopathogenic effect antigenicity at a 10−5 dilution (p<0.05). Conclusions QLCs from flavonoids from the leaves of BD have in vitro antiviral bioactivity against NDV at a virulence titter of 10-5 Tissue Culture Infectious Dose 50% (TCID50) in chicken kidney cell culture. QLCs may have the potential to be developed as medicinal compounds for the treatment of other human or animal viral infections

Human wharton’s jelly-derived mesenchymal stem cells minimally improve the growth kinetics and cardiomyocyte differentiation of aged murine cardiac c-kit cells in in vitro without rejuvenating effect

Cardiac c-kit cells show promise in regenerating an injured heart. While heart disease commonly affects elderly patients, it is unclear if autologous cardiac c-kit cells are functionally competent and applicable to these patients. This study characterised cardiac c-kit cells (CCs) from aged mice and studied the effects of human Wharton’s Jelly-derived mesenchymal stem cells (MSCs) on the growth kinetics and cardiac differentiation of aged CCs in vitro. CCs were isolated from 4-week- and 18-month-old C57/BL6N mice and were directly co-cultured with MSCs or separated by transwell insert. Clonogenically expanded aged CCs showed comparable telomere length to young CCs. However, these cells showed lower Gata4, Nkx2.5, and Sox2 gene expressions, with changes of 2.4, 3767.0, and 4.9 folds, respectively. Direct co-culture of both cells increased aged CC migration, which repopulated 54.6 ± 4.4% of the gap area as compared to aged CCs with MSCs in transwell (42.9 ± 2.6%) and CCs without MSCs (44.7 ± 2.5%). Both direct and transwell co-culture improved proliferation in aged CCs by 15.0% and 16.4%, respectively, as traced using carboxyfluorescein succinimidyl ester (CFSE) for three days. These data suggest that MSCs can improve the growth kinetics of aged CCs. CCs retaining intact telomere are present in old hearts and could be obtained based on their self-renewing capability. Although these aged CCs with reduced growth kinetics are improved by MSCs via cell–cell contact, the effect is minimal

Enhancing the Anticancer Activity of Squamocin for Breast Cancer Treatment Using Nanodiamond Nanoparticles: An In Vivo Study

Squamocin is one of the annonaceous acetogenins produced by the Annonaceae family and displays potent anti-cancer activity against cancer cell lines. This study aimed to investigate the growth inhibition activity of squamocin coupled with nanodiamond on rats (Rattus norvegicus)-induced breast cancer. Twenty-five female R. norvegicus were divided into five groups (n = 5), including normal control (without any treatment), negative control, group treated with nanodiamond only (ND), group treated with squamocin only (SQ), and the group treated with squamocin coupled with nanodiamond (NDSQ). All of the animal models were induced for breast cancer, except for the normal control group. Breast cancer induction was performed using two doses of N-nitroso-N-methylurea (NMU) injection (50 and 30 mg/kg body weight) intraperitoneally and waited for 22 weeks until the tumor was detected to formed. Nanodiamond coupled with squamocin were administered by intraperitoneal injection (1.5 mg/kg body weight) for 5 weeks, one injection per 3 days. This study showed that the treatment with squamocin coupled with nanodiamond (NDSQ) significantly reduced the proliferation (Ki-67) and induced apoptosis (Caspase-3) of breast cancer cells, corresponding to the reduction of the thickness of the mammary ductal epithelium (p&lt;0.001) and the lower level of CA-153 in serum. In addition, the treatment significantly reduced the malondioldehyde (MDA) and PI3KCA and increased the p53 level significantly. Altogether, in this study, we are the first to report the anti-cancer activity of squamocin in rat-induced breast cancer and the potency of nanodiamond as a carrier of squamocin to increase its anti-cancer activity

Annonacin and Squamocin Conjugation with Nanodiamond Alters Metastatic Marker Expression in Breast Cancer Cell Line

Breast cancer can perform metastasis to distant organs and cause more than 90% of malignancy-related deaths. The anti-metastasis potency of nanodiamond-conjugated annonacin and squamocin against MCF-7 cells is currently studied. First, IC50 determination of both free annonacin and squamocin to evaluate their potency as cytotoxic agents. Upon getting the IC50 value, both compounds are conjugated into nanodiamonds. Drug loading efficiencies of nanodiamond-conjugated annonacin and squamocin are 88.9% and 89.1%, respectively. Meanwhile, the ND-annonacin and ND-squamocin complex size is 150-300 nm based on SEM imaging. Subsequently, cell viability assessment of MCF-7 was performed with six cohort designs, namely, K (control cell), AN (annonacin), SQ (squamocin), NDAN (nanodiamond-conjugated annonacin), and NDSQ (nanodiamond-conjugated squamocin). Both IC50 and cell viability are assessed by MTT assay after 24 h incubation. All cohorts also underwent gene expression analysis subject to the metastasis markers CTNND1 (catenin delta 1), NOTCH4, and C-JUN. Here, the IC50 of both free annonacin (4.52 µg/ml) and squamocin (10.03 µg/ml) are more than IC50 of potent anticancer (&lt; 4 µg/ml) for pure compounds. However, nanodiamond conjugation to both compounds can decrease cell viability better than free compounds. Compared to K, nanodiamond-conjugated annonacin and squamocin significantly decreases cell viability after 24 h incubation. Bioinformatics analysis confirmed significant pro-metastasis (C-JUN and NOTCH4) upregulation and anti-metastasis (CTNND1) downregulation in tumors compared to normal. Recent findings demonstrated that nanodiamond-conjugated annonacin can significantly upregulate CTNND1 and significantly downregulate C-JUN and NOTCH4. Even so, nanodiamond-conjugated squamocin upregulate CTNND1 but not significantly and significantly downregulate C-JUN and NOTCH4