Systematic and meta-analysis of Mycobacterium avium subsp. paratuberculosis related type 1 and type 2 diabetes mellitus.

Global increase in diabetes (DM) prevalence necessitated the need to establish the association between DM and environmental triggers including MAP (Mycobacterium avium subsp. paratuberculosis) that have been postulated to play a role in DM etiopathology for effective management. The present investigation aimed to assess the odds ratio (OR) presenting the association between MAP and DM. MAP-related DM studies were systematically retrieved from 6 databases until 31 September 2021 according to PRISMA principles for data abstraction. The abstracted dataset was fitted to the fixed-effects (FE) and random-effects (RE) models using the Mantel-Haenszel approach. Sixteen studies involving 2072 participants (1152 DM patients (957 type 1 diabetes mellitus (T1DM) & 195 type 2 diabetes mellitus (T2DM)) and 920 healthy controls) met the inclusion criteria. Results revealed a significant association between anti-MAP antibodies (abs) seroprevalence and T1DM (FE: OR 7.47, 95% CI 5.50-10.14, p value < 0.0001; RE: OR 7.92, 95% CI 4.39-14.31, p < 0.0001) and MAP DNA with T1DM (FE: OR 4.70 (95% CI 3.10-7.13, p value < 0.0001), RE: OR 3.90 (95% CI 0.93-16.38, p value = 0.06)). Both anti-MAP abs and MAP DNA based meta-analyses had medium heterogeneity (I2 = 47.2-61.0%). Meanwhile, no significant association between MAP and T2DM (FE: OR 1.13, 95% CI 0.54-2.37, p value = 0.74; RE: OR 1.19; 95% CI 0.34-4.12, p value = 0.69), its OR magnitude exceeded 1 and prediction interval (0.09-15.29) suggest possibility of association between the duo in the future. The leave-one-out sensitivity analysis depicts a robust meta-analysis in all cases. In conclusion, the study manifests a positive association between MAP and T1DM, highlighting that MAP prevention and environmental control would indubitably revolutionize T1DM management. Also, its projects possible link between MAP and T2DM as more data becomes available. However, it remains elusive whether MAP triggers T1/T2DM or a mere comorbidity in T1/T2DM. Epidemiological activities to fill the global/regional data gaps on MAP-related T1DM and T2DM are advocated in order to assess the burden of MAP-related DM and improve their clinical management.

Systematic review and meta-analysis of Mycobacterium avium subsp. paratuberculosis as environmental trigger of multiple sclerosis.

Mycobacterium avium subsp. paratuberculosis (MAP) has been identified as one of the environmental agents that causes multiple sclerosis (MS). The global prevalence of MS has been upsurging over the years; however, efforts to divulge the role of MAP in MS have been limited. As a result, the present study aimed at assessing the odd ratios (ORs) associated MAP with the risk of MS. MAP-related MS data were obtained from 6 databases using the terms 'multiple sclerosis' or 'MS' and 'paratuberculosis' without regard for time or language restrictions following PRISMA standards. A total of 2,538 participants' data from 12 studies presenting anti-MAP antibodies and MAP DNA from 4 studies were fitted in random-effects (RE) and fixed-effects (FE) meta-analytic models. Furthermore, the between-study heterogeneity was measured using I2-values with a significant limit set at an I² > 75%. Analytical rigor and publication bias was determined using leave-one-out-analytics, Egger's tests, and p-curve analysis. In the FE and RE models, anti-MAP antibodies data significantly associated MS risk with MAP as 10.71 OR (95%-CI [7.78; 14.74], p-value < 0.0001) and 12.76 OR (95%-CI [8.13; 20.02], p-value < 0.0001) respectively, with an I2 value of 34.9% (95%-CI [0.0%; 67.2%]; p-value = 0.11). Similarly, the MAP DNA dataset in FE significantly present MS risk due to MAP as 5.53 OR (95%-CI [3.54; 8.66], p-value< 0.0001) while, RE showed 5.27 OR (95%-CI [3.22; 8.60], p = 0.0017), with an I2-value = 0.0% (95%-CI [0.0%; 84.7%]; p-value = 0.71). Eggers' test, on the other hand, found publication bias in anti-MAP antibodies data (intercept = 1.61, 95% CI: 0.45 - 2.77, t = 2.72, p = 0.021), but not in MAP DNA dataset (intercept = -5.57, 95% CI: -20.44 - 9.29, t = -0.74, p = 0.54). The robustness of the meta-analyses was demonstrated by all sensitivity analyses. In addition, there is no evidence of p-hacking observed (right-skewness test (PFull < 0.001, PHalf <0.001; statistical power ≥ 94% (95%-CI: 72.5%-99%)). In conclusion, the synthesis revealed a strong association between MAP and MS, indicating that MAP is a significant environmental agent that may trigger MS. Thus, early screening of MAP in MS cases may assist in the therapeutic approach to its management/treatment. Therefore, future studies should be tailored towards the role of MAP in the severity of MS phenotypes, as well as address global data gaps and low disease surveillance.

Aqueous extract of bay leaf (Laurus nobilis) ameliorates testicular toxicity induced by aluminum chloride in rats.

Background and Aim: Human exposure to aluminum is inevitable, and one of the most adverse health effects of aluminum is a decrease in male fertility rates. Therefore, this study investigated the ameliorative effects of an aqueous extract from Laurus nobilis-bay leaf (BL) on aluminum chloride (AlCl3)-induced testicular toxicity in rats. Materials and Methods: Twenty-four Wistar rats were divided into four groups (n = 6, each group): The control (group 1) received normal saline; Group 2 animals were intraperitoneally administered with 30 mg/kg body weight (BW) AlCl3; and Groups 3 and 4 were co-administered AlCl3 with 125 or 250 mg/kg BW of BL extract, respectively, for 21 days. Testes, epididymis, and blood samples were collected. Testicular plasma enzyme activity was measured using a spectrophotometric assay, while concentrations of inflammatory biomarkers were determined using enzyme-linked immunosorbent assay kits. Results: There was a significant increase (p < 0.05) in testicular enzyme activity in the group treated with AlCl3. However, there was no significant (p > 0.05) difference in testicular enzyme activity in groups co-administered AlCl3 and BL extract as compared with that in control. There was a significant (p < 0.05) increase in testicular nitrite concentration in the AlCl3-treated group, whereas the administration of BL extract significantly (p < 0.05) decreased nitrite concentration in Groups 3 and 4. Furthermore, the administration of BL extracts increased sperm count and improved the morphology of the testes in AlCl3-treated rats. Flavonoids, phenolic compounds, alkaloids, tannin, glycosides, saponin, anthraquinones, and steroids were identified in BL extract, with alkaloids and glycosides being the most abundant. Conclusion: Aqueous extract from BL ameliorated the toxic effect of AlCl3 and exhibited anti-inflammatory properties by inhibiting nitrite production while improving sperm count and morphology in AlCl3-treated rats. The bioactivity of the extract may be attributed to the presence of a wide range of phytochemicals. Therefore, BL aqueous extract could be a promising source of novel compounds with male fertility-promoting and anti-inflammatory properties.

Pleurotus ostreatus and Lentinus subnudus supplemented diets restore altered acetylcholinesterase and butyrylcholinesterase activities and improve antioxidant status in transgenic Drosophila melanogaster model.

Pleurotus ostreatus (P. ostreatus) and Lentinus subnudus (L. subnudus) have been used by the locals for the management of Alzheimer's disease (AD) but with scant scientific sources. The aim of this study is to assess the neuroprotective properties of P. ostreatus and L. subnudus using transgenic Drosophila melanogaster flies (TDMF). The activity of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), as well as the antioxidant status of TDMF raised on a diet supplemented with P. ostreatus and L. subnudus were determined. The flies were raised on a diet devoid of supplements or supplemented with P. ostreatus or L. subnudus (1% and 5% inclusion) for 7 days. Afterward, AChE and BChE activities, as well as catalase and total thiol level, were determined. The reactive oxygen species (ROS) and malondialdehyde (MDA) levels were also determined in the flies raised on a diet devoid of supplement and on supplemented diets. Meanwhile, flies raised on P. ostreatus- and L. subnudus-supplemented diets exhibited a significant reduction in the activity of AChE and BChE in comparison with the controls. Also, supplemented diets significantly (p < 0.05) enhance catalase activity and improve total thiol level, while ROS and MDA levels were observed to be reduced in all the flies raised on the supplemented diets in comparison with the controls. In summary, reduction in the activity of AChE and BChE, as well as improved antioxidant status in TDMF, could be some of the mechanisms through which P. ostreatus and L. subnudus exhibit anti-AD properties. Nevertheless, L. subnudus exhibits a better neuroprotective effect than P. ostreatus.

Studies on peroxidase production and detection of Sporotrichum thermophile-like catalase-peroxidase gene in a B acillus species isolated from Hogsback forest reserve, South Africa.

This study sought to determine the process conditions for optimum peroxidase production by a B acillus species (Bacillus sp. FALADE-1-KX640922) isolated from Hogsback forest reserve in South Africa and characterize the peroxidase gene in the bacteria. We optimized peroxidase production by manipulating the environmental and nutritional parameters under submerged fermentation. Subsequently, the gene encoding heme-peroxidase was determined through nested polymerase chain reaction and Sanger DNA sequencing. The studied bacteria had maximum peroxidase production at pH 8, 30 °C and 150 rpm. The addition of guaiacol to lignin fermentation medium enhanced peroxidase production by over 100 % in the studied bacteria. However, the other lignin monomers (veratryl alcohol, vanillin, vanillic acid and ferulic acid) repressed the enzyme activity. Modification of the fermentation medium with ammonium sulphate gave the maximum peroxidase yield (8.87 U mL-1). Under the predetermined culture conditions, Bacillus sp. FALADE-1 expressed maximum specific peroxidase activity at 48 h (8.32 U mg-1). Interestingly, a search of the sequenced gene in PeroxiBase showed 100% similarity to Sporotrichum thermophile catalase-peroxidase gene (katG), as well, the deduced protein sequence clustered with bacterial catalase-peroxidases and had a molecular weight of about 11.45 kDa with 7.01 as the estimated isoelectric point. Subsequently, the nucleotide sequence was deposited in the National Center for Biotechnology Information (NCBI) repository with the accession number MF407314. In conclusion, Bacillus sp. FALADE-1 is a promising candidate for improved peroxidase production.

Biochemical and molecular characterization of a novel dye-decolourizing peroxidase from Raoultella ornithinolytica OKOH-1.

The increase in industrial demand for peroxidases has necessitated the search for novel peroxidase with excellent industrial versatility. Raoultella ornithinolytica OKOH-1 is a new ligninolytic bacteria with peroxidase production potential. However, there is paucity of information on characterization of peroxidase from Raoultella species and its application potential in bioremediation. In this study, we characterized peroxidase from Raoultella ornithinolytica OKOH-1 (RaoPrx) for the first time using biochemical approach and bioinformatics; and as well investigated the dye-decolourization potential of the enzyme. RaoPrx oxidized various substrates, with pyrogallol giving the optimum activity. It had an optimum activity at pH 6 and was stable over a pH range of 5.0-7.0 with residual activity of above 40% after 120 min of incubation. The enzyme showed an optimum activity at 50 °C and was very stable at higher temperatures (50-70 °C) with residual activity of above 70% after 120 min. The enzyme was remarkably stable at 50 °C as it retained over 90% of its original activity after 120 min. The peroxidase activity was enhanced by Ag+, Cu2+, Zn2+and Fe2+, but was inhibited by Ca2+, Mg2+, Ba2+, Al3+, Co2+, NaN3 and EDTA. Furthermore, molecular characterization suggests RaoPrx as a novel dye-decolourizing peroxidase (DyP-type) family belonging to Class B, with estimated mo1ecular weight of 17.587 kDa and isoelectric point of 4.51, this is further confirmed by its remarkable dye-decolourizing activity on congo red and melanin in this study. This, therefore, indicates its application potential in textile dyes remediation and development of cosmetic agent.

Agrowastes utilization by Raoultella ornithinolytica for optimal extracellular peroxidase activity.

The industrial applications and prospects of microbial peroxidase are on the upwards trend, thus necessitating the search for sources with high turnaround time. Actinobacterial species have been a major source of peroxidase for the obvious reasons of having robust metabolite expression capabilities. However, other bacteria species have been underexplored for peroxidase production, hence the motivation for the investigation into the peroxidase production potential of Raoultella ornithinolytica OKOH-1 (KX640917). The bacteria expressed optimum specific peroxidase activity of 16.48 ± 0.89 U mg-1 , which is higher than those previously reported. The optimal fermentation conditions were pH 5 (3.44 ± 0.64 U mL-1 ), incubation temperature of 35 °C (5.25 ± 0.00 U mL-1 ), and agitation speed of 150 rpm (9.45 ± 2.57 U mL-1 ), with guaiacol and ammonium chloride as the best inducer and nitrogen supplement, respectively. On valorization of agrowastes as a sole carbon source for the secretion of peroxidase, sawdust gave the best peroxidase yield (15.21 ± 2.48 U mg-1 ) under solid-state fermentation. Also, a nonperoxide-dependent enzyme activity, which suggests probable laccase activity, was observed. The ability of the bacteria to utilize agrowastes is highly economical and as well a suitable waste management strategy. Consequently, R. ornithinolytica OKOH-1 is a promising industrial strain with dexterity for enhanced peroxidase production.

Ligninolytic enzymes: Versatile biocatalysts for the elimination of endocrine-disrupting chemicals in wastewater.

Direct municipal wastewater effluent discharge from treatment plants has been identified as the major source of endocrine-disrupting chemicals (EDC) in freshwaters. Consequently, efficient elimination of EDC in wastewater is significant to good water quality. However, conventional wastewater treatment approaches have been deficient in the complete removal of these contaminants. Hence, the exploration of new and more efficient methods for elimination of EDC in wastewater is imperative. Enzymatic treatment approach has been suggested as a suitable option. Nonetheless, ligninolytic enzymes seem to be the most promising group of enzymes for EDC elimination, perhaps, owing to their unique catalytic properties and characteristic high redox potentials for oxidation of a wide spectrum of organic compounds. Therefore, this paper discusses the potential of some ligninolytic enzymes (laccase, manganese peroxidase, and versatile peroxidase) in the elimination of EDC in wastewater and proposes a new scheme of wastewater treatment process for EDC removal.

Peroxidase production and ligninolytic potentials of fresh water bacteria Raoultella ornithinolytica and Ensifer adhaerens.

Interest in novel ligninolytic bacteria has remained topical due to, in part, the maneuverability of the bacterial genome. Conversely, the fungal genome lacks the dexterity for similar maneuverability thus, posing challenges in the fungal enzyme yield optimization process. Some impact of this situation includes the inability to commercialize the bio-catalytic process of lignin degradation by fungi. Consequently, this study assessed some fresh water bacteria isolates for ligninolytic and peroxidase properties through the utilization and degradation of model lignin compounds (guaiacol and veratryl alcohol) and the decolourization of selected ligninolytic indicator dyes; Azure B (AZB), Remazol Brilliant Blue R (RBBR) and Congo Red (CR). Bacterial strains with appreciable ligninolytic and peroxidase production potentials were identified through 16S rDNA sequence analysis and the nucleotide sequences deposited in the GenBank. About 5 isolates were positive for the degradation of both guaiacol (GA) and veratryl alcohol (VA) thus, accounting for about 17% of the test isolates. Similarly, AZB, RBBR and CR were respectively decolorized by 3, 2 and 5 bacterial strains thus, accounting for 10%, 7% and 17% of the test isolates. Two of the test bacterial strains were able to decolourize AZB, RBBR and CR respectively and these bacterial strains were identified as Raoultella ornithinolytica OKOH-1 and Ensifer adhaerens NWODO-2 with respective accession numbers as KX640917 and KX640918. Upon quantitation of the peroxidase activities; 5250 ± 0.00 U/L was recorded against Raoultella ornithinolytica OKOH-1 and 5833 ± 0.00 U/L against Ensifer adhaerens NWODO-2. The ligninolytic and dye decolourization properties of Raoultella ornithinolytica OKOH-1 and Ensifer adhaerens NWODO-2 marks for novelty particularly, as dyes with arene substituents were decolourized. Consequently, the potentials for the industrial applicability of these test bacterial strains abound as there is a dearth of information on organisms with such potentials.

Lignin peroxidase functionalities and prospective applications.

Ligninolytic extracellular enzymes, including lignin peroxidase, are topical owing to their high redox potential and prospective industrial applications. The prospective applications of lignin peroxidase span through sectors such as biorefinery, textile, energy, bioremediation, cosmetology, and dermatology industries. The litany of potentials attributed to lignin peroxidase is occasioned by its versatility in the degradation of xenobiotics and compounds with both phenolic and non-phenolic constituents. Over the years, ligninolytic enzymes have been studied however; research on lignin peroxidase seems to have been lagging when compared to other ligninolytic enzymes which are extracellular in nature including laccase and manganese peroxidase. This assertion becomes more pronounced when the application of lignin peroxidase is put into perspective. Consequently, a succinct documentation of the contemporary functionalities of lignin peroxidase and, some prospective applications of futuristic relevance has been advanced in this review. Some articulated applications include delignification of feedstock for ethanol production, textile effluent treatment and dye decolourization, coal depolymerization, treatment of hyperpigmentation, and skin-lightening through melanin oxidation. Prospective application of lignin peroxidase in skin-lightening functions through novel mechanisms, hence, it holds high value for the cosmetics sector where it may serve as suitable alternative to hydroquinone; a potent skin-lightening agent whose safety has generated lots of controversy and concern.