Medical Science

Permanent URI for this communityhttps://hdl.handle.net/10413/14008

Browse

Now showing 1 - 8 of 8

An investigation into kojic acid-associated mitochondrial toxicity and inflammation in melanoma cells (SK-MEL-1) = Uphenyo ku-esidi yekojiki ehlobaniswa nokukhinyabezeka kwemayithokhondriya nokuvuvukala ezinhlayiyeni zemelanoma (SK-MEL-1).
(2023) Suritham, Tamzin Kimera.; Chuturgoon, Anil Amichund.; Ghazi, Terisha.
ojic acid (KA), 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one, is used in agriculture, food, and cosmetics. KA is known to have antimicrobial, antifungal, antioxidant, and anti-inflammatory properties. The cosmetic industry's increasing interest in KA is due to its ability to inhibit tyrosinase activity resulting in skin lightening. The mitochondria play a key role in maintaining homeostasis and ensuring efficient melanin production. Therefore, mitochondrial dysfunction has severe effects on the skin. This study investigates mitochondrial stress, antioxidant responses, protein kinase signalling and inflammation in human melanoma (SK-MEL-1) cells. The mitochondria are important in processing metabolites and supplying the cell with energy in the form of ATP. KA interacts with key mitochondrial homeostasis proteins. Our results found an increase in macromolecule damage specifically lipid peroxidation and protein oxidation. Due to oxidative conditions, increased Nrf2 expression was observed. LON protease is ATP-dependent and regulated by Sirtuin 3 expression. Mitochondrial function was affected illustrated by decreased ATP production leading to decreased LON protease and Sirtuin 3 protein expression. Following increased oxidative stress, KA suppressed the expression of protein kinases but increased inflammatory mediators. There was decreased expression of phospho-Akt, Akt, phospho-GSK3β, p38 and ERK1/2. The mediation of the NLRP3 inflammasome involves priming and activation. At concentrations with high proliferation, NFκB gene and protein expression was activated. The protein kinase signalling pathways are known as mediators of inflammation; however, protein and gene expression of inflammatory mediators was increased following KA treatment. The inflammasome was subsequently activated as shown by an increase in intracellular caspase 1 levels as well as NLRP3, ILβ and IL-6 expression. KA induced mitochondrial stress and suppressed mitochondrial homeostasis proteins. The increased Nrf2 expression could have further downregulated LON protease expression and increased macromolecule damage. Oxidative conditions could have activated the inflammasome pathway independent of protein kinase signalling. In conclusion, KA displayed mitochondrial toxicity following acute exposure by suppressing mitochondrial homeostasis, protein kinase pathways and initiating inflammation. Iqoqa. I-esidi yeKojic (KA), 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4- eyodwa, iyasetshenziswa kwezolimo, ekudleni nasezimonyweni. I-KA yaziwa ngokuba ne-antimicrobial, antifungal, antioxidant, nezinto ezibanga ukuvuvukala. Luyakhula uthando lwezimboni zezimonyo ekuthandeni i-KA ngenxa yobukhona bayo ukuphazamisa ukusebenza kwetyrosinase okuholela ekutheni isikhumba sibe mhlophe. Kunokumqoka kakhulu okwenziwa imayithokhondriya ekugcineni usimamisoluzinzo lobunjalomzimba nokuqinisekisa ukukhiqizwa okwanele kwemvikelambala, imelanin. Ngakho ke, ukungasebenzi kwemayithokhondriya kunemithelela emibi esikhunjeni. Lolu cwaningo luphenya ngengcindezi yemayithokhondriya, ukusebenza kwe-antioxidant, ukukhombisa iphrotheyini khinasi nokuvuvukala kwezinhlayiya (SK-MEL-1) zemelanoma yomuntu. Imayithokhondriya ibalulekile ekuqhubeni umsebenzi wokugaya ukudla nokunika inhlayiya amandla ayisimo se-ATP. I-KA iyahlangana namaphrotheyini asemqoka osimamisoluzinzo lobunjalomzimba bemayithokhondriya. Imiphumela yethu yathola kukhula ukulimala emolekhiyulini enkulu okuyiliphidi iphreroksideyishini nokuncipha kwezinhlayiyabugesi ezihambayo zamaphrotheyini. Ngenxa yezimo zokuncipha kwezinhlayiyabugesi ezihambayo, kwabhekwa ukukhula kokuziveza kweNrf2. Okubalulekile empilweni nasekusebenzeni kwezinhlayiya, kuyi-LON, I-LON phrothizi kuncike kuyi-ATP futhi kulawulwa ukuziveza kweSirtuin 3. Umsebenzi wemayithokhondriya kwaphazamiseka kwaboniswa ukuncipha komkhiqizo we-ATP okwaholela ekuncipheni kweLON phrothizi nokuziveza kwephrotheyini iSirtuin 3. Ukulandela ukukhula kwengcindezi yokuncipha kwezinhlayiyabugesi zamaphrotheyini, i-KA yacindezela ukuziveza kwephrotheyini yekinases kodwa kwakhulisa ukuvuvukala kwezixhumanisi zengxube ezihlanganisayo. Kwaba nokuncipha kokuziveza kwephospho-Akt, i-Akt, i-phospho-GSK3β, i-p38 a ne-ERK1/2. Isihlanganisi seNLRP3 inflammasome sibandakanya ukulungiselela nokukhuthaza. Kusilinganisobungako esineproliferation ephezulu, ukuziveza kofuzo lweNFκB kanye nephrotheyini kwakhuthazeka. Ukukhombisa izindlela kwephrotheyini ikinase kwaziwa ngokuthi ukuvuvukala kwezixhumanisi; nokho, ukuziveza kwezixhumanisi zamaphrotheyini nawofuzo avuvukele kwakhula kulandela ukwelashwa kweKA. I-inflammasome yakhuthazwa njengoba yayiboniswa ngokukhula kwamazinga loku-1 lezinhlayiya zokufanayo kwecaspase nokuziveza kweNLRP3, i--β ne- IL-6. I-KA iletha ingcindezi yemayithokhondriya ibuye icindezele amaphrotheyini osimamisoluzinzo lobunjalomzimba bemayithokhondriya. Ukukhula kokuziveza kweNrf2 bekungeza ukwehlisa ukulawulwa kokuziveza kweLON phrothizi nokukhula kokulimala kwemolekhiyuli enkulu. Izimo zokuncipha kwezinhlayiyabugesi ezihambayo ngabe kukhuthaze izindlela ze-inflammasome ezizimele ezikhombisa iphrotheyini yekhinasi. Ucwaningo lwaphetha ngokuthi i-KA yabonisa ubuthi bemayithokhondriya kulandela ukungavimbeki kwabo okunamandla ngokuthi bucindezele usimamisoluzinzo lobunjalomzimba lwemayithokhondriya, izindlela zephrotheyini khinasi nokuqala kokuvuvukala.
Drug transporter expression and genetic polymorphisms in HIV endemic settings = Indlela yokuthutheka kwemithi emzimbeni nesakhiwo esingxube sofuzo ezimweni zokubhebhetheka kwesandulela ngculazi.
(2023) Zondo, Nomusa Margaret.; Archary, Derseree.; Sobia, Parveen.
Pre-exposure prophylaxis (PrEP) in the form of oral Truvada® remains the standard of care for HIV prevention in South Africa. Despite the availability of PrEP, HIV infections continue in young women significantly more than in men. Clinical trials testing antiretrovirals containing tenofovir as topical or oral PrEP formulations in African women, produced inconsistent patterns of efficacies against HIV. Effectiveness of oral and topical PrEP is dependent on adequate drug delivery and availability to cells and tissues targeted by HIV. Our study, therefore, focused on how different biological factors: drug transporter expression, single nucleotide polymorphisms (SNPs) in drug transporter genes and genital inflammation modulate PrEP disposition in African women. We characterized drug transporter mRNA expression in two compartments, the female genital tract (FGT) and blood, at baseline, 3 and 6 months in 45 women taking oral PrEP-Truvada®. Additionally, the impact of SNPs in 393 women and genital inflammation in 45 women on circulating tenofovir and drug transporter mRNA expression were determined. SNPs in drug transporter genes: ABCB1 3435G>A; ABCC1 198217T>C; ABCC2 1249G>A; ABCC4 3463T>C; ABCC4 4131A>C and ABCC4 4976A>G were evaluated using real-time PCR. mRNA expression of efflux P-gp, MRP-2, MRP-4, MATE-1 and influx OAT-1 and OAT-3 drug transporters was evaluated using quantitative real-time PCR. Genital inflammation was measured in cervicovaginal specimens using a 28-cytokine multiplexed platform. Results showed that ABCC4 4976A>G and ABCC4 3463T>C SNPs alter circulating tenofovir differently. While the ABCC4 4976A>G SNP significantly increased the mRNA expression of the ABCC4 gene (p=0.0132), there was inverse association with circulating tenofovir (p=0.018). In contrast, although the ABCC4 3463T>C SNP did not significantly impact mRNA expression of the ABCC4 gene, it was significantly and directly associated with circulating tenofovir (p<0.05). Correlation analyses showed moderately significant associations between the mRNA expression of the influx drug transporter OAT-1 in the FGT and blood pre- and post- PrEP exposure (rs<1, p<0.05). In contrast efflux drug transporters P-gp, MATE-1, MRP-2 and MRP-4 showed significance after PrEP initiation (3 and 6 months) (rs<1, p<0.05). For pro-inflammatory cytokines, linear mixed models showed negatively correlated trends between IL-1β and MCP-1 and influx drug transporter OAT-1 and OAT-3 (p<0.1), while IL1Rα and TNF-α showed these correlations with efflux drug transporters MRP-2 and MRP-4 (p<0.1). Collectively our results suggested that PrEP disposition can be modified through a convergence of host genetics and different biological factors: drug transporter expression, SNPs in drug transporter genes and inflammation. Findings from such studies may be used to better understand PrEP pharmacokinetics and aid in the implementation of optimal PrEP dosages. This 14 will ultimately inform on effective and safe PrEP for HIV prevention especially in vulnerable and at-risk African women. Iqoqa. ENingizimu Afrika ipre-exposure prophylaxis (PrEP) oral-Truvada® kuseyiyona ndlela yokunakekela ekuvimbeleni isandulela ngculazi, i-HIV. Kodwa ukutheleleka nge-HIV kuyaqhubeka kakhulu kwabesifazane abasebancane. Ukuvivinywa kwemithi lapho kuhlolwa i-PrEP egcotshwayo/neyasemlonyeni kulabo besifazane abangama-Afrika kuveza izimo ezingazinzile ekulweni ne-HIV. Ukuphumelela kwale mithi egcotshwayo/neyasemlonyeni kuncike kakhulu ekuhambisekeni komuthi okwanele nasebukhoneni bama-cells aqondwe ngqo yi-HIV; izinto ezihambisana nomzimba ezibalulekile zibonakele ekulawuleni ukusebenza kwe-PrEP ezindaweni ezithelelekile. Lolu cwaningo, lwabheka ukuthi izimo zomzimba: indlela yokuthuthwa komuthi emzimbeni, isakhiwo esisodwa ekuthuthweni komuthi emzimbeni isingle nucleotide polymorphisms (SNPs) kanye nokuvuvukala kwezitho zangasese kunomthelela muni ekusebenzeni kwePrEP kwabesifazane abangama-Afrika. Kwakhethwa isithuthi semithi i-mRNA-expression ngezindlela ezimbili: umgudu wezitho zangasese kwabesifazane, ifemale genital tract (FGT) kanye negazi, ekuqaleni kocwaningo, izinyanga ezi-3 neziyi- 6 kwabesifazane abangama-N=45 abathatha i-PrEP-Truvada® ngomlomo. Kwabe sekubhekwa i-mRNA-expression ye-P-gp, MRP-2, MRP-4, MATE-1 kanye ne-OAT-1 kanye ne-OAT-3 okuyizithuthi zemithi ezahlolwa kusetshenziswa ucwaningozibalo lwereal-time-PCR. Umthelela we-SNPs (N=393) kanye nokuvuvukala kwezitho zangasese (N=45) ekuzungeziseni i-tenofovir kanye nesithuthimithi i-mRNA-expression kwabonakala. Ukubonakala kwe-SNPs kwizithuthimithi zofuzo: ABCB1[3435G>A]; ABCC1[198217T>C]; ABCC2[1249G>A]; ABCC4[3463T>C]; ABCC4[4131A>C] kanye ne-ABCC4[4976A>G] kwahlolwa kusetshenziswa ireal-time-PCR. Ukuvuvukala kwezitho zangasese kwakalwa kumasampula ayethathwe ebuntwini babesifazane kusetshenziswa indlela ye-28-cytokine-multiplexed platform. Imiphumela yakhombisa ukuthi i-ABCC4[4976A>G] kanye ne-ABCC4[3463T>C] SNP ishintsha ukuzungeza kwetenofovir ngendlela ehlukile. I-ABCC4[4976A>G] SNP yakhulisa kakhulu i-mRNA-expression ye-ABCC4 gene (p=0.0132), kodwa yanomthelela ophambene ekuzungezeni kwetenofovir (p=0.018). Uma kuqhathaniswa, yize i-ABCC4[3463T>C] SNP ingabanga namthelela otheni kwi-mRNA-expression yofuzo i-ABCC4, yayamana kakhulu nokukhula ekuzungeziseni itenofovir (p<0.05). Ukuhlaziya kwalokhu kuhlobana kwakhombisa ukuhambisana okubalulekile phakathi kwe-mRNA-expression ye-OAT-1 kwiFGT kanye negazi ngaphambi nangemuva kokusetshenziswa kwe-PrEP. Kanti i-P-gp, MATE-1, MRP-2 kanye ne-MRP-4 kwakhombisa ukubaluleka emuva kokuqalwa kwe-PrEP ezinyangeni ezi-3 kuya kweziyi-6 (rs<1, p<0.05). Ekuvuvukaleni kwezitho zangasese, izindlela eziqondile ezingxube zakhombisa ukungahlobani phakathi kwe-IL-1β kanye ne-MCP-1 ene-OAT-1 kanye ne-OAT-3; IL-1Rα kanye ne-TNF-α ene-MRP-2 kanye ne-MRP-4 (p<0.1). Seyihlangene yonke le miphumela yakhombisa ukuthi ukusebenza kwe-PrEP kuyashintshashintsha ngokubambisana kwezimo ezahlukene emzimbeni: yindlela umuthi othutheka ngayo, ama-SNPs, kanye nokuvuvukala kwezitho zangasese. Imiphumela yalolu cwaningo ingasetshenziselwa ukuba kuqondwe kangcono amandla okusebenza kwe-PrEP kanye nokuqalwa kokukala ubungako bomuthi we-PrEP ngendlela efanele. Ngaleyo ndlela, kungaba nokusebenziseka ngempumelelo nangendlela ephephile kwe-PrEP ukuze kunqandwe isandulela ngculazi kwabesifazane bama-Afrika abasengcupheni.
An exploration of binge drinking and coping behaviour during covid-19 among students in a major tertiary institution in KwaZulu-Natal.
(2023) Faborode, Joy Adebowale.; Kathree, Tasneem.
Background: The COVID-19 pandemic has profoundly impacted human lives. At the emergence of the novel disease, several restrictive measures, including lockdowns, were implemented to mitigate the spread of COVID-19. These measures created stressful challenges that affected people’s mental wellbeing, including that of tertiary students. There is a dearth of information on the strategies students use to cope with COVID-19-related stress. This study aimed to understand how students experienced and coped with changes attributed to the lockdowns in South Africa, including factors that influenced alcohol use among students at a major tertiary institution in KwaZulu Natal during the COVID-19 lockdown. Method: A qualitative approach was used. Twenty students were recruited from two campuses at the University of KwaZulu-Natal (UKZN), Durban, South Africa, using purposive sampling. Individual indepth interviews were conducted using a semi-structured interview guide comprising open-ended questions. The NVivo software program was used for analysis. Results: The majority (60%) of participants were male and ranged from 20 to 36 years old. The results of this study indicate drinking patterns among the study sample. Results indicate that despite implementing an alcohol sale ban during the COVID-19 lockdowns, alcohol use was not eliminated, but there was some reduction in the intake of alcohol. Apart from alcohol restrictions, some factors influencing drinking included drinking location and people with whom participants consumed alcohol. Many participants also indicated that they preferred to consume alcohol with friends because it helped them to bond with their friends and improved their social interactions. In addition, over 50% of the students stated that they drank alcohol because they felt happy, socialized with others, had fun, and that they enjoyed the taste. In contrast, only a few (four) reported drinking as a coping mechanism. Respondents were also aware of the negative consequences of drinking alcohol, especially when it is in large quantities. Results also indicate that half of the participants felt stressed, depressed, anxious and sad during the lock down. In addition, they also experienced problems related to eating and sleeping. The study highlighted the various coping mechanisms participants used to deal with stress. These included emotion-based coping strategies such as social support, sleeping, exercise, reading, watching television, listening to music, and maintaining a positive attitude, problem-based coping strategies (e.g., positive thinking and planning), as well as avoidance forms of coping (such as ignoring the situation). Conclusion: This study found that alcohol misuse was common in this sample of university students prior to the onset of COVID-19, and they experienced some distress during the COVID-19 lockdown. Factors that influenced alcohol use were also identified in this study sample which provided insight into how they experienced and coped with changes directly caused by the lockdowns in South Africa. 11 Despite these findings, sampling students from only one tertiary institution in KwaZulu Natal and being unable to interview students in their home language or the language of fluency if this was not English are identified as limitations. This study recommends that health promotion and education on alcohol use and coping strategies should be encouraged at tertiary institutions to curb alcohol misuse and improve students’ wellbeing.
Molecular epidemiology of Antibiotic-Resistant Escherichia coli from companion animals attending veterinary practices in Durban, KwaZulu-Natal, South Africa.
(2023) Ntuli, Nondumiso Lungile.; Essack, Sabiha Yusuf.; Mbanga, Joshua.; Abia Akebe, Luther King.
Background: Companion animals are globally documented to harbour antibiotic-resistant E. coli. This study aimed to investigate the molecular epidemiology of antibiotic-resistant E. coli from companion animals presenting at veterinary practices in Durban, KwaZulu-Natal, South Africa. Methods: E. coli were isolated on selective media from rectal swabs sampled from dogs and cats attending veterinary practices in Durban, KwaZulu-Natal, South Africa. All isolates were confirmed using real-time polymerase chain reaction (PCR) of the uidA gene. Antibiotic susceptibility testing was done against 20 antibiotics using the Kirby-Bauer disk diffusion method. Selected antibiotic-resistance genes (ARGs) that confer resistance to third-generation cephalosporins (blaTEM, blaSHV, and blaCTX-M), tetracycline (tetA, and tetB), and tigecycline (tetX/X2, tetX3, and tetX4), were detected using conventional PCR. PCR amplicons were confirmed by DNA sequencing and bioinformatics analysis. Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR) was carried out to determine the clonality of E. coli (101) isolates that showed resistance to at least one antibiotic. Results: A total of 330 E. coli isolates from dogs (234) and cats (96) formed the study sample. Overall resistance was high in tetracycline (24.2%), ampicillin (18.8%), trimethoprim-sulfamethoxazole (14%), cephalexin (11.2%) and nalidixic acid (9.7%). Whilst lower resistance was observed in amikacin (0.3%), ceftazidime (0.3%), and piperacillin-tazobactam (0.6%). Third-generation cephalosporin-resistant E. coli retrieved from cats (26%) was more prevalent compared to dogs (9.8%). E. coli from dogs (2.1%) and cats (2%) were resistant to forth-generational cephalosporins. E. coli (3%) retrieved from dogs was resistant to tigecycline, which is regarded as a medically important antimicrobial (MIA) in human medicine. No resistance was observed against carbapenems. Thirty-five (10.6%) E. coli were multidrug-resistant (MDR) and exhibited twenty-two different phenotypic patterns. Amongst the E. coli that were not susceptible to third-generation cephalosporin, and tetracycline, it was observed that the blaCTX-M-15 (8%), and tetA (24%) were the most prevalent resistance genes. Thirty-one (9.3%) isolates were non-susceptible to third-generation cephalosporins and had the corresponding extended-spectrum beta-lactamase (ESBL) genes. The blaCTX-M-15 type gene was prevalent in all 25 E. coli isolates that tested positive for the blaCTX-M. The blaTEM-1 (17) was the second most prevalent β-lactamase gene. A total of 80/330 (24%) isolates were phenotypically not susceptible to tetracycline and carried either one, or both of tetA and tetB resistance genes. Only one tetracycline-resistant E. coli isolate did not harbour either tetA, or tetB genes. The blaSHV, tetX/X2, tetX3, and tetX4 were not detected in all the isolates. Using a 75% similarity cut-off, forty-eight clusters with isolates from both dogs and cats were identified. The ERIC-PCR types depicted a variety of clusters within veterinary practices in Durban, indicating that a high diversity of E. coli is in circulation in Durban, South Africa. Conclusion: Companion animals are reservoirs of antibiotic-resistant E. coli and ARGs. However, there was no evidence of transmission of antibiotic-resistant E. coli in Durban, South Africa. Resistance of E. coli from companion animals to MIA for humans is of particular concern and requires measures to control the spread of antibiotic-resistant bacteria, and ARGs between companion animals, veterinary practice personnel, and owners.
Mortality trends during the first three waves of the covid- 19 pandemic at an urban district hospital in KwaZulu-Natal.
(2023) Hirachund, Omishka.; Naidoo, Mergan.
Introduction Severe Acute Respiratory Syndrome Corona Virus 2 (SARS COV 2) is the virus responsible for the COVID -19 (C19) pandemic. South Africa (SA) experienced multiple periods of increased transmission during which tertiary, regional and central hospitals were overwhelmed, resulting in a low acceptance rate of referrals from district hospitals (DHs). Thus, many severely ill, complex patients were managed at DHs while awaiting an Intensive Care Unit (ICU) bed. This study aims to describe mortality trends in a comparative analysis of the first three C19 waves at Wentworth Hospital (WWH). Literature Review Known risk factors for mortality are older age; male sex; Black African, Coloured and Indian compared to white race; admission in the public sector; comorbid diseases and obesity. Waves 2 and 3 had higher mortality rates compared to wave 1. Methods The study is a single-centre retrospective analysis of WWH’s clinical records and included all patients infected with C19 (based on clinical, biochemical or radiological features suggestive of infection) who were admitted and subsequently demised in-hospital during the defined waves. Data was collected using a pre-piloted data extraction tool. Demographic and presenting features of the patients along with investigations and management strategies were compared by the primary investigator across the three waves. Results Wave one, two and three yielded case fatality rates of 14.5%, 27.6% and 6.3%, respectively, and crude fatality rates of 16.7%, 33.0% and 12.2%, respectively. Black Africans were less likely to demise during the third wave (odds ratio (OR) 0.54; 95% confidence interval (CI) 0.31 to 0.94). Obesity was most prevalent in the second wave (OR 1.87; CI 1.01 to 3.46). Patients in the second wave had clinical frailty scores of less than five (OR 2.51; CI 1.56 to 4.03). Severe ground glass appearance on chest radiographs was most common during the second wave (OR 2.37; CI 1.49 to 3.77). Conclusion The beta variant dominated the second wave and was the most virulent, as highlighted by the highest case- and crude fatality rates. This study identified the need to understand if case fatality 2 rates and mortality trends at a DH were significantly higher than those at regional or tertiary hospitals. It is hoped that this study will provide clinical and hospital managers, and provincial and national healthcare policy makers with insight into challenges faced in the health system in the public health sector and allow implementation of improved public health and planning strategies for future pandemics.
Strategic application of in silico drug discovery approaches to discover novel TB drugs = Ukusetshenziswa komqondosu womuthi wokwelapha i-in silico ngezindlelakwenza ukuze kutholakale imithi yokwelapha i-TB emisha.
(2023) Kisten, Kimona.; Mhlongo, Ndumiso Nhlakanipho.; Kumalo, Hezekiel Mathambo.
Tuberculosis is one of the major causes of mortality worldwide due to the onset of bacterial infection. It remains a continuous field of study as a result of the emergence of drug resistant strains whereby first- and second-line drugs are ineffective. Variations associated with proteins in the bacteria, Mycobacterium tuberculosis, can be attributed largely to poor compliance of patients and the existence of co-morbidities within a person, inevitably leading to coinfections and a diminished immune response. This evolution of the bacteria therefore calls for extensive research to be carried out on enhanced drug design and development techniques. Re-evaluation of previously identified drug targets, determination of newly viable drug targets and the identification and design of small molecule inhibitors form a basis on the forefront of this research. Computer aided drug design techniques provide a novel method exponentially gaining popularity. Molecular modelling utilizing in silico developed methods, paired with drug repurposing, pose a viable, cost effective and efficient solution for drug design strategies. The use of chemical interaction data associated with small molecules forming complexes with drug targets of interest help understand the behaviour and mechanism of a protein before graduating to wet method techniques. Using the fundamentals of docking, molecular dynamics and virtual screening, various small molecules with the potential to provide extensive inhibition capability can be identified. This study investigates three major drug targets of Mycobacterium tuberculosis (Mtb): Enoyl-[acyl-carrier-protein] reductase (inhA), β-ketoacyl ACP synthase (KasA), and Dihydropteroate synthase (DHPS/folP1) involved in the mycolic acid and folate pathways. Various tools inclusive of gene ontology, network-based inference, virtual screening and tailored pharmacophore as a function of molecular modelling and drug repurposing were used to identify potential potent inhibitors and comprehend the understanding of the structural changes, conformations and interactions associated with the protein and the response to suggested drug hits with the potential to affect an overall protein structure in consideration with the formation of a complex. This approach can potentially serve as a platform to the development and discovery of novel drugs against a wide range of drug targets. Iqoqa. Isifo sofuba singezinye zezimbangela ezinkulu zokushona emhlabeni jikelele ngenxa yokuthathelwana kwezifo zamagciwane. Silokhu siqhubeka nokuba wumkhakha ocwaningwayo ngenxa yokuqubuka kwezinhlobo ezingezweli emithini yokwelapha lapho imithi esetshenziswe ezingeni lokuqala nelesibili ingasebenzi. Umehluko ohlobene nezakhamzimba amaphrotheyni asegciwaneni iMycobacterium tuberculosis, kungahlotshaniswa kakhulu nokuhambisana okungekuhle kweziguli nobukhona bezinye izifo kumuntu, okuholela ekuthelelekeni ngokuningi nokwenza izinga lamasosha omzimba ehle. Le nguqukomumo yegciwane ibiza ukuba kube nocwaningo olunzulu okumele lwenziwe ngohlelo lwemithi ephuculiwe namasu okuluphucula. Ukuhlola kabusha kwemithi ebihlonzwe esikhathini esedlule ukuhlonzwa kokuhloswe ngemithi yokwelapha nesakhiwo sezivimbi zamamolekhyuli amancane kuyisisekelo esiphambili kulolu cwaningo. Amasukhono emithi ehlanganiswe ngokwekhompyutha ahlinzeka indlela esazanywa enokuthandwa okukhula kakhulu. Ukuqondisa amamolekhyuli asetshenziswa ezindleleni ezakhelwe i-in silico, ahambelaniswa nokusetshenziselwa ezinye izifo kwemithi, okuqhamuka isixazululo esinezindleko eziphansi nezisebenza ngezindlela zamasu okwakha imithi. Ukusetshenziswa kwemininingo yokuxutshwa kwamakhemikhali okuhlobene namamolekhyuli amancane kwakha izinhlanganisela zemithi okusoshwe ukusiza ukuqonda insebenzo kanye nendlela yephrotheyni ngaphambi kokuba kwedlulelwe emaswini ayizindlela zokumanzisa. Kusetshenziswa izingqikithi zokuzimelelisa, amadayinamikhi amamolekhyuli nokuskrina ungekho endaweni, amamolekhyuli amancane ayizinhlobo ezehlukene ezingakwazi ukuhlinzeka ukukwazi ukuvimbela okusezingeni elikhulu okungahlonzwa. Lolu cwaningo luphenya izinhlobo ezintathu zemithi esoshelwe ukusetshenziselwa i-Mycobacterium tuberculosis (Mtb): i-Enoyl-[acyl-carrier-protein] reductase (inhA), i-β-ketoacyl ACP synthase (KasA), neDihydropteroate synthase (DHPS/folP1) efakwe emigudwini yemycolic acid nefolate. Amathuluzi ehlukene ezinsizakusebenza ezisuselwa ekucwaningeni ngobunjalobukhona bofuzo, ukuqagulwa okususelwa ebuxhakaxhakeni, ukuskrina ungekho lapho kusetshenzelwa khona nensebenzomithi ehleliwe njengokomgomo wokwakhiwa kwamamolekhyuli nokusetshenziswa ngendlela entsha kwemithi kwenziwelwa ukuhlonza izivimbinsebenzobuthi ezikhona nokuzwa ukuqonda ushintsho lokomumo, okuhambelana nokuxhumana okuhambelana namaphrotheyni nempendulo yemithi ephakanyisiwe engaba nomthelela emumweni ophelele wephrotheyni uma kubhekwa isakhiwo senkimbingxube. Leli su lingakwazi ukuba yinkundla yentuthuko nokuthola imithi esazanywa esetshenziselwa izinhloso ezehlukene zokwelapha.
Type I, II, and III interferon responses in the female genital tract.
(2024) Ngubane, Slindile Brilliant Lyzeth.; Sivro, Aida.
Abstract available in PDF.
Waist circumference, waist-to height ratio, or body mass index: which is the better predictor of hypertension in patients living with diabetes mellitus in low-to-middle-income countries?
(2022) Konar, Kylie Divashnee.; Pillay, Somasundram.
Background Hypertension (HPT) in low and middle-income countries (LMICs) remains a leading preventable factor for death and disability. Approximately 20-60% of patients living with diabetes (PLWD) have HPT which doubles the mortality risk and accelerates the progression of complications. Obesity is a well-known preventable risk factor for HPT. Despite this, countries in Sub-Saharan Africa (SSA) faces an increasing challenge of obesity. Current evidence on anthropometric indices as a predictor for HPT in PLWD remain unclear. Methods A scoping review was performed to determine the association between anthropometry and HPT in PLWD in LMICs in SSA, by using PubMed, Google, Scopus and Cochrane between 2011- 2021. A total of 4590 records were identified. The associations between body mass index (BMI), waist circumference (WC) or waist-to-height ratio (WTHR) in PLWD and HPT in LMICs in SSA were assessed. Results We analyzed 21 studies with 11 057 patients included in this review. BMI was the most common anthropometric index used with more than 80% of studies suggesting a positive association with HPT. Varying associations between other anthropometric indices and HPT were found. Conclusions Our scoping review highlighted a positive association between HPT and anthropometry in most studies. Limited data was available comparing the different anthropometric indices. We found that additional studies are warranted to evaluate anthropometric indices in PLWD.

Browse

Browsing Medical Science by SDG "SDG3"