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Herein, the aim is to discuss the current knowledge of microbiome and periodontal diseases. Current treatment strategies include mechanical therapy such as root planing, scaling, deep pocket debridement and antimicrobial chemotherapy as an adjuvant therapy. Among promising therapeutic strategies, dental probiotics and oral microbiome transplantation have gained attention, and may be used to treat bacterial imbalances by competing with pathogenic bacteria for nutrients and adhesion surfaces, as well as probiotics targeting the gut microbiome. Development of strategies to prevent and treat periodontal diseases are warranted as both are highly prevalent and can affect human health. Further studies are necessary to better comprehend the microbiome in order to develop innovative preventative measures as well as efficacious therapies against periodontal diseases.

Sea cucumbers are worm-like, leathery bodied, benthic, marine organisms with a branched gonad. There are over 900 species, and these organisms are capable of changing their mechanical state, regenerating their small appendages, and digestive tract. Additionally, sea cucumbers possess both commercial and therapeutical value. Furthermore, it is thought that the metabolites these organisms possess may give rise to their therapeutical value. The use of sea cucumbers in therapy can be traced back to the Ming dynasty, where they were eaten for their tonic properties against constipation, hypertension, and rheumatism. A plethora of studies have been conducted, whereby different metabolites were extracted from sea cucumbers and tested for different therapeutic properties. Herein, we review and discuss the anti-cancer, anti-microbial, anti-coagulant, anti-diabetic, antioxidant, and anti-inflammatory properties of the sea cucumber by assessing literature on PubMed and Google Scholar. Furthermore, the genome and epigenome of these remarkable species is discussed. With the immense data supporting the therapeutic properties of sea cucumbers, further studies are warranted, in order to develop novel and innovative therapeutic compounds for the benefit of human health from these fascinating marine organisms.

Given the opportunity and access, pathogenic protists (Balamuthia mandrillaris and Naegleria fowleri) can produce fatal infections involving the central nervous system. In the absence of effective treatments, there is a need to either develop new antimicrobials or enhance the efficacy of existing compounds. Nanocarriers as drug delivery systems are gaining increasing attention in the treatment of parasitic infections. In this study, novel nanocarriers conjugated with amphotericin B and curcumin were evaluated for anti-amoebic efficacy against B. mandrillaris and N. fowleri. The results showed that nanocarrier conjugated amphotericin B exhibited enhanced cidal properties against both amoebae tested compared with the drug alone. Similarly, nanocarrier conjugated curcumin exhibited up to 75% cidal effects versus approx. 50% cidal effects for curcumin alone. Cytopathogenicity assays revealed that the pre-treatment of both parasites with nanoformulated-drugs reduced parasite-mediated host cellular death compared with the drugs alone. Importantly, the cytotoxic effects of amphotericin B on human cells alone were reduced when conjugated with nanocarriers. These are promising findings and further suggest the need to explore nanocarriers as a means to deliver medicine against parasitic infections.

Colorectal cancer is the third most diagnosed cancer worldwide and the second most prevalent cause of cancer-related mortality. It is believed that alterations within the gut microbiome may impact the development and progression of cancer. Additionally, the diet an individual maintains and the amount of alcohol consumed can alter the microbiome, thus impacting the development of colorectal cancer. A diet focused on fiber intake is considered beneficial, as it contains short-chain fatty acids such as butyrate, which have antitumor properties. Furthermore, current treatment strategies, such as chemotherapy, have various side effects. In this review, we discuss the role of the gut microbiome and oral bacteria in relation to colorectal cancer. We also deliberate on the role of diet and alcohol consumption in the development of colorectal cancer. Moreover, the influence of the various metabolites within the gut and the importance of gut inflammation in the development of colorectal cancer are explained. Finally, potential therapies such as fecal microbiota transfer and post/prebiotics are elaborated on. To further comprehend risk factors in the development of colorectal cancer, future studies are warranted to determine the precise mechanisms of action between the gut microbiome and carcinogenesis in order to develop therapies that may target gut microbial dysbiosis.

Naegleria fowleri (N. fowleri) is a free-living, unicellular, opportunistic protist responsible for the fatal central nervous system infection, primary amoebic meningoencephalitis (PAM). Given the increase in temperatures due to global warming and climate change, it is estimated that the cases of PAM are on the rise. However, there is a current lack of awareness and effective drugs, meaning there is an urgent need to develop new therapeutic drugs. In this study, the target compounds were synthesized and tested for their anti-amoebic properties against N. fowleri. Most compounds exhibited significant amoebicidal effects against N. fowleri; for example, 1h, 1j, and 1q reduced N. fowleri’s viability to 15.14%, 17.45% and 28.78%, respectively. Furthermore, the majority of the compounds showed reductions in amoeba-mediated host death. Of interest are the compounds 1f, 1k, and 1v, as they were capable of reducing the amoeba-mediated host cell death to 52.3%, 51%, and 56.9% from 100%, respectively. Additionally, these compounds exhibit amoebicidal properties as well; they were found to decrease N. fowleri’s viability to 26.41%, 27.39%, and 24.13% from 100%, respectively. Moreover, the MIC50 values for 1e, 1f, and 1h were determined to be 48.45 µM, 60.87 µM, and 50.96 µM, respectively. Additionally, the majority of compounds were found to exhibit limited cytotoxicity, except for 1l, 1o, 1p, 1m, 1c, 1b, 1zb, 1z, 1y, and 1x, which exhibited negligible toxicity. It is anticipated that these compounds may be developed further as effective treatments against these devastating infections due to brain-eating amoebae.

Naegleria fowleri and Balamuthia mandrillaris are opportunistic protists, responsible for fatal central nervous system infections such as primary amoebic meningoencephalitis (PAM) and granulomatous amoebic encephalitis (GAE) with mortality rates higher than 90%. Threatening a rise in cases is the increase in temperature due to global warming. No effective treatment is currently available. Herein, nanotechnology was used to conjugate Zinc oxide with Ampicillin, Ceftrixon, Naringin, Amphotericin B, and Quericitin, and the amoebicidal activity and host cell cytotoxicity of these resulting compounds were investigated. The compounds ZnO-CD-AMPi, ZnO-CD-CFT, ZnO-CD-Nar, ZnO-CD-AMB, and ZnO-CD-QT were found to reduce N. fowleri viability to 35.5%, 39.6%, 52.0%, 50.8%, 35.9%, and 69.9%, respectively, and B. mandrillaris viability to 40.9%, 48.2%, 51.6%, 43.8%, and 62.4%, respectively, when compared with their corresponding controls. Furthermore, the compounds reduced N. fowleri-mediated and B. mandrillaris-mediated host cell death significantly. Additionally, the compounds showed limited cytotoxicity against human cells; cell toxicity was 35.5%, 36.4%, 30.9%, 36.6%, and 35.6%, respectively, for the compounds ZnO-CD-AMPi, ZnO-CD-CFT, ZnO-CD-Nar, ZnO-CD-AMB, and ZnO-CD-QT. Furthermore, the minimum inhibitory concentrations to inhibit amoeba growth by 50% were determined for N. fowleri and B. mandrillaris. The MIC50 for N. fowleri were determined to be 69.52 µg/mL, 82.05 µg/mL, 88.16 µg/mL, 95.61 µg/mL, and 85.69 µg/mL, respectively; the MIC50 of the compounds for B. mandrillaris were determined to be 113.9 µg/mL, 102.3 µg/mL, 106.9 µg/mL, 146.4 µg/mL, and 129.6 µg/mL, respectively. Translational research to further develop therapies based on these compounds is urgently warranted, given the lack of effective therapies currently available against these devastating infections.

The free-living amoeba Acanthamoeba castellanii is responsible for the central nervous infection granulomatous amoebic encephalitis and sight-threatening infection Acanthamoeba keratitis. Moreover, no effective treatment is currently present, and a combination drug therapy is used. In this study, twelve DNA minor groove binders (MGBs) were synthesized and tested for their antiamoebic activity via amoebicidal, encystation, excystation, and cytopathogenicity assays. It was found that the compounds MGB3, MGB6, MGB22, MGB24, and MGB16 significantly reduce amoeba viability to 76.20%, 59.45%, 66.5%, 39.32%, and 43.21%, respectively, in amoebicidal assays. Moreover, the compounds MGB6, MGB20, MGB22, MGB28, MGB30, MGB32, and MGB16 significantly inhibit Acanthamoeba cysts, leading to the development of only 46.3%, 39%, 30.3%, 29.6%, 27.8%, 41.5%, and 45.6% cysts. Additionally, the compounds MGB3, MGB4, MGB6, MGB22, MGB24, MGB28, MGB32, and MGB16 significantly reduce the re-emergence of cysts to trophozoites, with viable trophozoites being only 64.3%, 47.3%, 41.4%, 52.9%, 55.4%, 40.6%, 62.1%, and 51.7%. Moreover, the compounds MGB3, MGB4, and MGB6 exhibited the greatest reduction in amoeba-mediated host-cell death, with cell death reduced to 41.5%, 49.4%, and 49.5%. With the following determined, future in vivo studies can be carried out to understand the effect of the compounds on animal models such as mice.

Naegleria fowleri and Balamuthia mandrillaris are free-living, opportunistic protists, distributed widely in the environment. They are responsible for primary amoebic meningoencephalitis (PAM) and granulomatous amoebic encephalitis (GAE), the fatal central nervous infections with mortality rates exceeding 90%. With the rise of global warming and water shortages resulting in water storage in tanks (where these amoebae may reside), the risk of infection is increasing. Currently, as a result of a lack of awareness, many cases may be misdiagnosed. Furthermore, the high mortality rate indicates the lack of effective drugs available. In this study, secondary metabolites from the plants Rinorea vaundensis and Salvia triloba were tested for their anti-amoebic properties against N. fowleri and B. mandrillaris. Three of the nine compounds showed potent and significant anti-amoebic activities against both N. fowleri and B. mandrillaris: ursolic acid, betulinic acid, and betulin. Additionally, all compounds depicted limited or minimal toxicity to human cells and were capable of reducing amoeba-mediated host cell death. Moreover, the minimum inhibitory concentration required to inhibit 50% of amoebae growth, the half-maximal effective concentration, and the maximum non-toxic dose against human cells of the compounds were determined. These effective plant-derived compounds should be utilized as potential therapies against infections due to free-living amoebae, but future research is needed to realize these expectations.