Complementary Medicine a Costly Risk in Management of Chronic Knee Osteoarthritis? A Case Report

@#Knee osteoarthritis is the commonest cause of knee pain in the elderly. It is characterized by unresolved pain, limitation of motion and reduced quality of life. Total knee arthroplasty (TKA) is a safe and effective method in treating chronic knee osteoarthritis. We report a rare case of a seventy-seven-year-old Chinese female with multiple comorbidities and bilateral degenerative osteoarthritis who had sought services of traditional and complementary medicine (TCM) for pain relief. The patient experienced unresolved pain and superficial skin scars following the unregulated procedure. This paper aims to outline the importance of awareness among surgeons regarding the unregulated practice of TCM that may exacerbate chronic osteoarthritis, joint synovitis, influence the surgical approach for future procedures with the presence of scars and prosthetic joint infection risk.

Computational drug screening against the SARS-CoV-2 Saudi Arabia isolates through a multiple-sequence alignment approach.

COVID-19 is a rapidly emerging infectious disease caused by the SARS-CoV-2 virus currently spreading throughout the world. To date, there are no specific drugs formulated for it, and researchers around the globe are racing against the clock to investigate potential drug candidates. The repurposing of existing drugs in the market represents an effective and economical strategy commonly utilized in such investigations. In this study, we used a multiple-sequence alignment approach for preliminary screening of commercially-available drugs on SARS-CoV sequences from the Kingdom of Saudi Arabia (KSA) isolates. The viral genomic sequences from KSA isolates were obtained from GISAID, an open access repository housing a wide variety of epidemic and pandemic virus data. A phylogenetic analysis of the present 164 sequences from the KSA provinces was carried out using the MEGA X software, which displayed high similarity (around 98%). The sequence was then analyzed using the VIGOR4 genome annotator to construct its genomic structure. Screening of existing drugs was carried out by mining data based on viral gene expressions from the ZINC database. A total of 73 hits were generated. The viral target orthologs were mapped to the SARS-CoV-2 KSA isolate sequence by multiple sequence alignment using CLUSTAL OMEGA, and a list of 29 orthologs with purchasable drug information was generated. The results showed that the SARS CoV replicase polyprotein 1a had the highest sequence similarity at 79.91%. Through ZINC data mining, tanshinones were found to have high binding affinities to this target. These compounds could be ideal candidates for SARS-CoV-2. Other matches ranged between 27 and 52%. The results of this study would serve as a significant endeavor towards drug discovery that would increase our chances of finding an effective treatment or prevention against COVID19.

Human Dental Pulp Stem Cells (DPSCs) Therapy in Rescuing Photoreceptors and Establishing a Sodium Iodate-Induced Retinal Degeneration Rat Model

BACKGROUND@#Different methods have been used to inject stem cells into the eye for research. We previously explored the intravitreal route. Here, we investigate the efficacy of intravenous and subretinal-transplanted human dental pulp stem cells (DPSCs) in rescuing the photoreceptors of a sodium iodate-induced retinal degeneration model. @*METHODS@#Three groups of Sprague Dawley rats were used: intervention, vehicle group and negative control groups (n = 6 in each). Intravenous injection of 60 mg/kg sodium iodate (day 0) induced retinal degeneration. On day 4 postinjection of sodium iodate, the rats in the intervention group received intravenous DPSC and subretinal DPSC in the right eye; rats in the vehicle group received subretinal Hank’s balance salt solution and intravenous normal saline; while negative control group received nothing. Electroretinogram (ERG) was performed to assess the retinal function at day 0 (baseline), day 4, day 11, day 18, day 26, and day 32. By the end of the study at day 32, the rats were euthanized, and both their enucleated eyes were sent for histology. @*RESULTS@#No significant difference in maximal ERG a-wave (p = 0.107) and b-wave, (p= 0.153) amplitude was seen amongst the experimental groups. However, photopic 30 Hz flicker amplitude of the study eye showed significant differences in the 3 groups (p = 0.032). Within the intervention group, there was an improvement in 30 Hz flicker ERG response of all 6 treated right eyes, which was injected with subretinal DPSC; while the 30 Hz flicker ERG of the nontreated left eyes remained flat. Histology showed improved outer nuclear layer thickness in intervention group; however, findings were not significant compared to the negative and vehicle groups. @*CONCLUSION@#Combination of subretinal and intravenous injection of DPSCs may have potential to rescue cone function from a NaIO3 -induced retinal injury model.

Antidiabetic potential and high synergistic antibacterial activity of silver nanoparticles synthesised with Musa Paradisiaca tepal extract

@#This work investigates the Musa Paradisiaca plant and its tepal extracts. The research findings show that the tepal extracts of M. Paradisiaca contain high phytochemical activity. Hence we can conclude that these plants have a number of beneficial properties. Phytochemical analysis concludes that the plant is rich in flavonoids, phenolic compounds, tannins, terpenoids, and phytosterol. In the current work, silver nanoparticles (AgNPs) have revealed the antioxidant properties of M. Paradisiaca. The results show that the methanolic extracts of these tepals exhibit antioxidant potential and are also sources of natural antioxidant compounds, though comparatively, AgNPs have shown the best antioxidant activity. This work investigates the link between the ethnopharmacological statements and the bioactive constituents found in M. Paradisiaca toward all probable markers for cervical cancer via in vivo studies and molecular docking, to form a pharmacophore setting for the active target. However, most of the mechanisms of action of herbal medicines are not in total agreement, and the information collected from their traditional remedies over the years must not be neglected. Hence, it is sensible to investigate the options available in herbal medicine for cancer progression. Biosynthesised AgNPs are principally spherical and nanosized. It was also found that tepalmediated AgNPs exhibit excellent antimicrobial efficacy against tested human pathogens. This green method can be used as a better alternative source than the chemical fabrication of nanomaterials and the biosynthesised nanoparticles can be used in antibacterial medicines. The methanolictepal extract of M. Paradisiaca with AgNPs displayed proficient antidiabetic properties in the diabetes rat model and so could have a possible development for medical use in the future

Human Dental Pulp Stem Cells (DPSCs) Therapy in Rescuing Photoreceptors and Establishing a Sodium Iodate-Induced Retinal Degeneration Rat Model

BACKGROUND@#Different methods have been used to inject stem cells into the eye for research. We previously explored the intravitreal route. Here, we investigate the efficacy of intravenous and subretinal-transplanted human dental pulp stem cells (DPSCs) in rescuing the photoreceptors of a sodium iodate-induced retinal degeneration model. @*METHODS@#Three groups of Sprague Dawley rats were used: intervention, vehicle group and negative control groups (n = 6 in each). Intravenous injection of 60 mg/kg sodium iodate (day 0) induced retinal degeneration. On day 4 postinjection of sodium iodate, the rats in the intervention group received intravenous DPSC and subretinal DPSC in the right eye; rats in the vehicle group received subretinal Hank’s balance salt solution and intravenous normal saline; while negative control group received nothing. Electroretinogram (ERG) was performed to assess the retinal function at day 0 (baseline), day 4, day 11, day 18, day 26, and day 32. By the end of the study at day 32, the rats were euthanized, and both their enucleated eyes were sent for histology. @*RESULTS@#No significant difference in maximal ERG a-wave (p = 0.107) and b-wave, (p= 0.153) amplitude was seen amongst the experimental groups. However, photopic 30 Hz flicker amplitude of the study eye showed significant differences in the 3 groups (p = 0.032). Within the intervention group, there was an improvement in 30 Hz flicker ERG response of all 6 treated right eyes, which was injected with subretinal DPSC; while the 30 Hz flicker ERG of the nontreated left eyes remained flat. Histology showed improved outer nuclear layer thickness in intervention group; however, findings were not significant compared to the negative and vehicle groups. @*CONCLUSION@#Combination of subretinal and intravenous injection of DPSCs may have potential to rescue cone function from a NaIO3 -induced retinal injury model.

In Vitro Assessment of Biofilm Formation by Streptococcus pyogenes Isolates From Invasive and Non-invasive Samples With Diverse emm Type Profiles

@#Introduction: Biofilm is one of the important virulence factors that is responsible for the severity and progression of the Streptococcus pyogenes diseases. M-protein is involved in the irreversible attachment of S. pyogenes to surfaces during biofilm development. This study aims to determine the propensity of S. pyogenes to form biofilms and the molecular epidemiology of S. pyogenes isolates by emm typing. Methods: We screened 45 S. pyogenes isolates for the biofilm formation by Congo red agar (CRA) and quantified the biofilms by crystal violet microtiter-plate methods (CVMtP). The emm typing of all isolates was performed by conventional PCR with established primers according to the CDC protocol. Results: Majorities of S. pyogenes were isolated from non-invasive, 27 (60.0%) than invasive sources, 18 (40.0%). Regardless of invasiveness, 40 (88.9%) S. pyogenes isolates formed black colonies on CRA, while 43 (95.6%) of the isolates demonstrated various degrees of biofilm formation by CVMtP method. A total of 30 different emm types and subtypes were identified. No new emm types/subtypes were detected. The predominant emm types/subtypes were emm1, emm63, emm18.21, emm91, and emm97.4 which each gene accounted for 7.0%. All emm types/subtypes of S. pyogenes produced biofilms by CVMtP method except emm17.2 and emm57 which were isolated from non-invasive sources. Conclusions: Biofilm-producing S. pyogenes strains of various sources are genetically diverse and biofilm phenotypes are inherent to individual characteristic rather than specific emm type. Nonetheless, higher propensity of GAS to form biofilms warrants better management strategies to avoid treatment failures in the future.

Mucoadhesive guargum hydrogel inter-connected chitosan-g-polycaprolactone micelles for rifampicin delivery.

Natural polymer guar gum has one of the highest viscosities in water solution and hence, these are significantly used in pharmaceutical applications. Guar gum inter-connected micelles as a new carrier has been developed for poor water soluble rifampicin drug. The hydrogel inter-connected micelle core was formulated as a hydrophilic inner and hydrophobic outer core by using guar gum/chitosan/polycaprolactone and the carrier interaction with rifampicin was confirmed by FT-IR. The morphological observations were carried out through TEM, SEM and AFM analysis. The encapsulation efficiency and in-vitro drug release behavior of prepared hydrogel based micelle system was analyzed by UV-vis spectrometry. The anti-bacterial activity against K. pneumoniae and S. aureus was studied by observing their ruptured surface by SEM. The cytotoxicity study reveals that the pure polymeric system has no toxic effect whereas drug loaded ones showed superior activity against THP-1 cells. From the cell apoptosis analyses, the apoptosis was carried out in a time dependent manner. The cell uptake behavior was also observed in THP-1 cells which indicate that the hydrogel based micelle system is an excellent material for the mucoadhesive on intracellular alveolar macrophage treatment.

Silver nanoparticle functionalized CS-g-(CA-MA-PZA) carrier for sustainable anti-tuberculosis drug delivery.

Recently, drug functionalized biodegradable polymers have been appreciated to be imperative to fabricate multi-drug delivery nanosystems for sustainable drug release. In this work, amphiphilic chitosan-grafted-(cetyl alcohol-maleic anhydride-pyrazinamide) (CS-g-(CA-MA-PZA)) was synthesized by multi-step reactions. The incorporation of rifampicin (RF) and entrapment of silver nanoparticles (Ag NPs) on CS-g-(CA-MA-PZA) polymer was carried out by dialysis technique. From the FT-IR experiment, the polymer modification, incorporation of drugs and the entrapment of Ag NPs on micelles were confirmed. The surface morphology of Ag NPs, polymeric system and drug loaded micelles was described by SEM, TEM and AFM techniques. In addition, the controlled release behaviour of CS-g-(CA-MA-PZA) micelles was studied by UV-Vis spectroscopy. In vitro cell viability, cell apoptosis and cellular uptake experiments shows that multi-drug delivery system could enhance the biocompatibility and higher the cytotoxicity effect on the cells. Since the prepared amphiphilic polymeric micelles exhibit spotty features and the system is a promising strategy for a novel candidate for immediate therapeutically effects for alveolar macrophages.

Anticancer potential of Alternanthera sessilis extract on HT-29 human colon cancer cells

Objective: To identify the bioactive extracts from Alternanthera sessilis and investigate its cytotoxicity potential against colon cancer cells, HT-29. Methods: This study examined the effects of three parts (aerial, leaf, stem) of whole plant on HT-29 colon cancer cell lines. Three different extracts from the plant parts were prepared by maceration technique using 80% ethanol. The anticancer activities were determined using MTT, clonogenic, cell motility and AOPI assay. The chemical composition profiling was analyzed by GC-MS. Results: Among three plant part extracts, leaf extract greatly suppressed the growth of colon cancer cells in time and dosage-dependent manner, followed by aerial and stem. The cytotoxicity results were rationalized with clonogenic, cell motility and AO/PI assay, where extract showed the most active activity compared to aerial and stem extracts. GC-MS analysis of leaf extract showed there were various recognized anti-cancer, anti-oxidant and anti-inflammatory compounds. Conclusions: Amid the screened extracts, the leaf extract exhibits the credible cytotoxic, anti-proliferative and apoptotic activity and hence, our findings call for additional research to conclude the active compounds and their mechanisms determining the apoptotic activity.

Nitric oxide participates in plant flowering repression by ascorbate.

In Oncidium, redox homeostasis involved in flowering is mainly due to ascorbic acid (AsA). Here, we discovered that Oncidium floral repression is caused by an increase in AsA-mediated NO levels, which is directed by the enzymatic activities of nitrate reductase (NaR) and nitrite reducatase (NiR). Through Solexa transcriptomic analysis of two libraries, 'pseudobulb with inflorescent bud' (PIB) and 'pseudobulb with axillary bud' (PAB), we identified differentially expressed genes related to NO metabolism. Subsequently, we showed a significant reduction of NaR enzymatic activities and NO levels during bolting and blooming stage, suggesting that NO controlled the phase transition and flowering process. Applying AsA to Oncidium PLB (protocorm-like bodies) significantly elevated the NO content and enzyme activities. Application of sodium nitroprusside (-NO donor) on Arabidopsis vtc1 mutant caused late flowering and expression level of flowering-associated genes (CO, FT and LFY) were reduced, suggesting NO signaling is vital for flowering repression. Conversely, the flowering time of noa1, an Arabidopsis NO-deficient mutant, was not altered after treatment with L-galacturonate, a precursor of AsA, suggesting AsA is required for NO-biosynthesis involved in the NO-mediated flowering-repression pathway. Altogether, Oncidium bolting is tightly regulated by AsA-mediated NO level and downregulation of transcriptional levels of NO metabolism genes.