Non-coding RNAs (ncRNAs) including microRNAs (miRs) and long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in immune cells development and function. Their expression is altered in different physiological and disease conditions, hence making them attractive targets for the understanding of disease etiology and the development of adjunctive control strategies, especially within the current context of mitigated success of control measures deployed to eradicate these diseases. In this review, we summarize our current understanding of the role of ncRNAs in the etiology and control of major human tropical diseases including tuberculosis, HIV/AIDS and malaria, as well as neglected tropical diseases including leishmaniasis, African trypanosomiasis and leprosy. We highlight that several ncRNAs are involved at different stages of development of these diseases, for example miR-26-5p, miR-132-3p, miR-155-5p, miR-29-3p, miR-21-5p, miR-27b-3p, miR-99b-5p, miR-125-5p, miR-146a-5p, miR-223-3p, miR-20b-5p, miR-142-3p, miR-27a-5p, miR-144-5p, miR-889-5p and miR-582-5p in tuberculosis; miR-873, MALAT1, HEAL, LINC01426, LINC00173, NEAT1, NRON, GAS5 and lincRNA-p21 in HIV/AIDS; miR-451a, miR-let-7b and miR-106b in malaria; miR-210, miR-30A-5P, miR-294, miR-721 and lncRNA 7SL RNA in leishmaniasis; and miR-21, miR-181a, miR-146a in leprosy. We further report that several ncRNAs were investigated as diseases biomarkers and a number of them showed good potential for disease diagnosis, including miR-769-5p, miR-320a, miR-22-3p, miR-423-5p, miR-17-5p, miR-20b-5p and lncRNA LOC152742 in tuberculosis; miR-146b-5p, miR-223, miR-150, miR-16, miR-191 and lncRNA NEAT1 in HIV/AIDS; miR-451 and miR-16 in malaria; miR-361-3p, miR-193b, miR-671, lncRNA 7SL in leishmaniasis; miR-101, miR-196b, miR-27b and miR-29c in leprosy. Furthermore, some ncRNAs have emerged as potential therapeutic targets, some of which include lncRNAs NEAT1, NEAT2 and lnr6RNA, 152742 in tuberculosis; MALAT1, HEAL, SAF, lincRNA-p21, NEAT1, GAS5, NRON, LINC00173 in HIV/AIDS; miRNA-146a in malaria. Finally, miR-135 and miR-126 were proposed as potential targets for the development of therapeutic vaccine against leishmaniasis. We also identify and discuss knowledge gaps that warrant for increased research work. These include investigation of the role of ncRNAs in the etiology of African trypanosomiasis and the assessment of the diagnostic potential of ncRNAs for malaria, and African trypanosomiasis. The potential targeting of ncRNAs for adjunctive therapy against tuberculosis, leishmaniasis, African trypanosomiasis and leprosy, as well as their targeting in vaccine development against tuberculosis, HIV/AIDS, malaria, African trypanosomiasis and leprosy are also new avenues to explore.

Oxidative stress is a state in which oxidants are produced in excess in the body’s tissues and cells, resulting in a biological imbalance amid the generation of reactive oxygen and nitrogen species (RONS) from redox reactions. In case of insufficient antioxidants to balance, the immune system triggers signaling cascades to mount inflammatory responses. Oxidative stress can have deleterious effects on major macromolecules such as lipids, proteins, and nucleic acids, hence, Oxidative stress and inflammation are among the multiple factors contributing to the etiology of several disorders such as diabetes, cancers, and cardiovascular diseases. Non-coding RNAs (ncRNAs) which were once referred to as dark matter have been found to function as key regulators of gene expression through different mechanisms. They have dynamic roles in the onset and development of inflammatory and oxidative stress-related diseases, therefore, are potential targets for the control of those diseases. One way of controlling those diseases is through the use of natural products, a rich source of antioxidants that have drawn attention with several studies showing their involvement in combating chronic diseases given their enormous gains, low side effects, and toxicity. In this review, we highlighted the natural products that have been reported to target ncRNAs as mediators of their biological effects on oxidative stress and several inflammation-associated disorders. Those natural products include Baicalein, Tanshinone IIA, Geniposide, Carvacrol/Thymol, Triptolide, Oleacein, Curcumin, Resveratrol, Solarmargine, Allicin, aqueous extract or pulp of Açai, Quercetin, and Genistein. We also draw attention to some other compounds including Zanthoxylum bungeanum, Canna genus rhizome, Fuzi-ganjiang herb pair, Aronia melanocarpa, Peppermint, and Gingerol that are effective against oxidative stress and inflammation-related disorders, however, have no known effect on ncRNAs. Lastly, we touched on the many ncRNAs that were found to play a role in oxidative stress and inflammation-related disorders but have not yet been investigated as targets of a natural product. Shedding more light into these two last points of shadow will be of great interest in the valorization of natural compounds in the control and therapy of oxidative stress- and inflammation-associated disorders.

Gaps in early and accurate diagnosis, effective drug control, and treatment monitoring are hindering the global eradication effort of tuberculosis. This infectious disease has become the deadliest worldwide before the outbreak of Covid-19. The search for new molecular biomarkers of tuberculosis will help to reverse this trend. Long non-coding RNAs (lncRNAs) have emerged as important regulators of the host immune response to infection, hence their link with the etiology and diagnosis of tuberculosis has attracted some attention from the research community. However, very little is known about their potential for the monitoring of tuberculosis treatment. This study aimed at assessing the potential of two lncRNAs: p50-associated Cyclooxygenase-2 Extragenic RNA (PACER) and Long Non-coding RNA 13 (LNC13) in the monitoring of tuberculosis treatment. This was a cross-sectional study carried out in Douala, Cameroon from December 2020 to August 2021. A quantitative real-time polymerase chain reaction followed by Cq analysis using the Livak method were performed to measure the relative expression levels of PACER and LNC13 in whole blood of healthy controls, patients with active pulmonary tuberculosis at the initiation of treatment, after two, five, and six months into treatment. Receiver Operating Characteristic curves analysis was Frontiers in Tropical Diseases frontiersin.org 01

Early diagnosis is crucial in controlling tuberculosis globally and in developing countries with the emergence of drug-resistant Mycobacterium tuberculosis strains. Long non-coding RNAs (lncRNAs) are promising tuberculosis diagnostic biomarkers. Two lncRNA diagnostic markers, lncRNA THRIL and lincRNA-p21, were studied as tuberculosis diagnostic biomarkers. This cross-sectional study was conducted at the Center of Respiratory Diseases of LAQUINTINIE hospital and the National Veterinary Laboratory of Douala from December 2020 to August 2021. The ability of lncRNAs to distinguish between 19 healthy controls, 15 latent tuberculosis, and 21 active tuberculosis was estimated using quantitative polymerase chain reaction and Receiver Operating Characteristic curve analysis. Our analysis showed that lncRNA THRIL and lincRNA-p21 were significantly upregulated (P <0.05) in active and latent tuberculosis compared with healthy controls. LincRNA-p21 expression was significantly increased (P <0.05) in active tuberculosis compared with latent tuberculosis, whereas lncRNA THRIL was not significantly affected (P ≥0.05). Both lncRNA THRIL and lincRNA-p21 showed excellent performance in classifying latent tuberculosis and healthy controls (AUC = 92.86%). Furthermore, lncRNA THRIL was good at discriminating active tuberculosis from healthy controls (AUC = 89.79%), while lincRNA-p21 showed excellent discriminating performance (AUC = 100%). LncRNA THRIL was identified as a poor discriminator of latent tuberculosis from active tuberculosis (AUC = 64.28%), while lincRNA-p21 showed excellent diagnostic performance in this distinction (AUC = 92.86%). Our cross-sectional study suggests that lncRNA THRIL and lincRNA-p21 are promising tuberculosis diagnostic biomarkers that can differentiate between latent and active infection.