Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson’s disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann–Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.

Garcinia celebica (G. celebica), an aromatic plant which is domestically planted for fruits and ornamental purposes, is exceptionally rich in important phytochemicals that may contribute to its medicinal properties. The mechanistic basis of cytotoxic action of G. celebica essential oil (EO-GC) in MCF-7, MCF-7/TAMR-1, and MCF-10A cell cultures was explored in this study. The study findings showed that the EO-GC potently inhibited the proliferation of the MCF-7 and MCF-7/TAMR-1 cells by 50% at 37.5 µg/mL and 18.8 µg/mL concentrations, respectively. In contrast, a higher concentration (77.5 µg/mL) of the essential oil was needed to inhibit the MCF-10A cells. These findings demonstrated that the EO-GC possesses selective cytotoxic effects by two-fold and four-fold towards the MCF-7 and MCF-7/TAMR-1 cells, respectively, than the MCF-10A cells. Flow cytometric analysis has proven that the EO-GC can effectively induce apoptotic cell death in the cultured MCF-7 and MCF-7/TAMR-1 cells, while having minimal effect on the MCF-10A cells. Therefore, these preliminary findings may add novel scientific data related to the potential therapeutic efficacy of the ethereal oil derived from G. celebica leaves.

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious threat to the global healthcare system. Ineffective and resistance to antibiotic treatments have increased morbidity and mortality rates worldwide.New and effective antibiotics are needed to combat against bacterial resistance. Endophytic fungi are crucial reservoirs of novel bioactive metabolites. In particular, the secondary metabolites show promising therapeutic potential, notably, antibacterial. This review discussed the emerging potential of endophytic fungi as anti-MRSA agents. The ecological sources of endophytic fungi were discussed with the synthesis of bioactive metabolites.The mode of antibacterial actions was elucidated to give a better understanding of the mechanisms involved. This review may serve as an important reference for future discovery and developments of anti-MRSA agents from endophytic fungi.

Humans ; United States ; Internship and Residency ; COVID-19 ; Emergency Medicine/education* ; Curriculum

Aims: This research was conducted to develop and characterize polyvinyl alcohol (PVA)/montmorillonite (MONT) clay incorporated with carvacrol (Carva) nanocomposite film as a potential material in wound dressing. Methodology and results: Organophilic MONT clay, which was initially modified from commercial MONT clay by cetyltrimethylammonium bromide (CTAB), was used in the polymerization process using PVA. The synthesized nanocomposites were visualized via transmission electron microscopy (TEM). The developed film (PVA/MONT/Carva nanocomposite film) was characterized via Fourier transform infrared (FTIR). The investigation on mechanical property and antimicrobial activity of the film was also performed. All nanocomposites are spherical, with a size of 92.8 ± 22.1 nm. The -OH stretch, C-H stretch, aromatic group, SiO stretch, and C-O from acetyl group were identified in the PVA/MONT/Carva nanocomposite films. During the chemical release test, carvacrol attained a plateau at 24 h, with a total release of 62.3%. This nanocomposite exhibited a severe detrimental influence on the growth of Gram-bacteria and yeasts, which represented a broad spectrum of antimicrobial agents. All test microorganisms showed approximately up to 82% reduction of microbial growth during the Hohenstein challenge test. Physically, the nanocomposite films were yellowish and apparent. The film was sturdy, flexible, elastic and consisted of excellent water holding capacity. Conclusion, significance and impact of study PVA/MONT/Carva nanocomposite film may have a useful potential to be merged in the pharmaceutical application, especially in wound dressing production.
Polyvinyl Alcohol ; Bentonite ; Wound Healing

Aims: Endophytic fungi are organisms that colonize living plant tissues without causing significant symptoms of diseases. They are known as the repository of bioactive compounds. This study was aimed to isolate endophytic fungi associated with Aloe vera and to assess their antimicrobial activity against the diabetic wound pathogens that result to lower limb amputations. Methodology and results: In this study, 84 endophytic fungi were isolated from A. vera by using 5% sodium hypochlorite and 70% ethanol as surface sterilants. On preliminary antimicrobial screening by agar plug assay, 12 (14.3%) isolates showed significant antagonistic activity on the test microorganisms. Two of the endophytes were identified as Aspergillus flavus and Colletotrichum gloeosporioides through morphological and molecular techniques. The fungal cultures fermented in shake flask were extracted subsequently with hexane, dichloromethane, ethyl acetate, and n-butanol. Ethyl acetate and dichloromethane extracts of A. flavus and C. gloeosporioides inhibited all test bacteria. The compounds in the extracts were seemed to be semi-polar in nature. On broth microdilution assay, minimal inhibitory and minimal lethality concentration of ethyl acetate extracts of the fungi were found in the range of 0.63−2.50 and 1.25−5.00 mg/mL, respectively. Conclusion, significance and impact of study This study reveals that A. vera harbours a wide diversity of endophytic fungi. A. flavus and C. gloeosporioides showing broad spectrum antimicrobial activity on wound pathogens may be potential sources of bioactive compounds. Further investigations should be conducted to isolate and identify the antimicrobial compound produced by these fungal isolates.
Endophytes--isolation & ; purification ; Aloe

Microbial wound infection prolonged the hospitalization and increase the cost for wound management. Silver is commonly used as antimicrobial wound dressing. However, it causes several adverse side effects. Hence, this study was aimed to evaluate the antimicrobial efficiency of Swietenia macrophylla seed extract on clinical wound pathogens. Besides, the bioactive constituents of the seed extract were also determined. S. macrophylla seeds were extracted with methanol by maceration method. The seed extract inhibited 5 test bacteria and 1 yeast on disc diffusion assay. The antibacterial activity was broad spectrum, as the extract inhibited both Gram positive and Gram negative bacteria. On kill curve analysis, the antibacterial activity of the seed extract was concentration-dependent, the increase of extract concentration resulted in more reduction of bacterial growth. The extract also caused 99.9% growth reduction of Bacillus subtilis relative to control. A total of 21 compounds were detected in gas chromatography-mass spectrometry analysis. The predominant compounds present in the extract were oleic acid (18.56%) and linoleic acid (17.72%). In conclusion, the methanolic extract of S. macrophylla seeds exhibited significant antimicrobial activity on clinical wound pathogens. Further investigations should be conducted to purify other bioactive compounds from the seeds of S. macrophylla.
Bacillus subtilis ; Bacteria ; Bandages ; Diffusion ; Gas Chromatography-Mass Spectrometry ; Gram-Negative Bacteria ; Hospitalization ; Linoleic Acid ; Meliaceae ; Methanol ; Methods ; Oleic Acid ; Silver ; Wound Infection ; Wounds and Injuries ; Yeasts

Aims: Diabetic patients with foot ulcer showed 150-fold increased risk of amputation, which is primarily caused by microbial infection. Silver ions are commonly incorporated into wound dressing to enhance the antimicrobial property. However, concerns have been expressed about the development of bacterial resistance to heavy metals. In this study, we extracted the nano-cellulose from medical cotton and reinforced with gelatin to develop a film for wound dressing. Methodology and results: Garcinia mangostana L pericarp extract was incorporated into the nano-cellulose film as antimicrobial finishing. The efficacy of the developed nano-cellulose film was evaluated on diabetic wound microorganisms. We observed cellulose nano crystals with an average length of 133.71 nm under transmission electron microscope. The developed film showed gradual release of the extract over a period of 48 h and no burst effect was observed. The film exhibited significant inhibitory activity on three Gram positive bacteria, three Gram negative and all filamentous fungi tested. On Hohenstein challenge test, all test microorganisms showed significant growth reduction, with the treatment of the film. We also noticed that the antimicrobial activity of the film sustained even after 20 washes. Conclusion, significance and impact of study Our results indicate that the G. mangostana L pericarp extract loaded nano-cellulose films exhibited significant inhibitory activity on diabetic wound microorganisms. The developed film can be potentially used to prevent foot ulcer infection among diabetic patients.

Helminthostachys zeylanica is a rare plant grows in lightly shaded areas. The fern was traditionally used as antipyretic and antiphlogistic agents. This study was aimed to evaluate the antibacterial potential of H. zeylanica on foodborne Bacillus cereus. The chemical composition of its ethanolic extract was also determined. The plant samples were collected at Kampung Kebun Relong, Kedah, Malaysia. The ethanolic extract showed significant inhibitory activity on B. cereus with a sizeable clear zone detected on disc diffusion assay. On broth microdilution assay, the MIC of the extract on B. cereus was 6.25 mg/ml and the MBC was 12.5 mg/ml. The inhibitory activity of the extract on B. cereus was bactericidal. In the growth dynamic study, the antibacterial efficacy of the extract was concentration dependent, where a lower colony forming unit count was obtained with increased extract concentration. The SEM micrograph of extract treated B. cereus cells showed invaginations of cell wall. The bacterial cell structure collapsed after 24 h exposure to the extract. The GCMS analysis of the extract showed that the major constituents of the extract were phenol (36.26%) and quercetin (29.70%). This study is important as it shows the potential use of H. zeylanica as an effective agent to control B. cereus related infections.
Bacillus cereus ; Bacillus ; Cell Wall ; Diffusion ; Ethanol ; Ferns ; Gas Chromatography-Mass Spectrometry ; Malaysia ; Phenol ; Plants ; Quercetin ; Stem Cells

The present study was undertaken to investigate the isolated compounds from the stem bark of Garcinia atroviridis as potential cholinesterase inhibitors and the ligand-enzyme interactions of selected bioactive compounds in silico. The in vitro cholinesterase results showed that quercetin (3) was the most active AChE inhibitor (12.65 ± 1.57 µg/ml) while garcinexanthone G (6) was the most active BChE inhibitor (18.86 ± 2.41 µg/ml). It is noteworthy to note that compound 6 was a selective inhibitor with the selectivity index of 11.82. Molecular insight from docking interaction further substantiate that orientation of compound 6 in the catalytic site which enhanced its binding affinity as compared to other xanthones. The nature of protein-ligand interactions of compound 6 is mainly hydrogen bonding, and the hydroxyl group of compound 6 at C-10 is vital in BChE inhibition activity. Therefore, compound 6 is a notable lead for further drug design and development of BChE selective inhibitor.
Butyrylcholinesterase ; Catalytic Domain ; Cholinesterase Inhibitors ; Cholinesterases ; Computer Simulation ; Drug Design ; Garcinia ; Hydrogen Bonding ; In Vitro Techniques ; Quercetin ; Xanthones