Biosynthesis of lactobionic acid: a systematic review.

Lactobionic acid is a comparatively less explored lactose derivative with impressive biofunctional qualities, and is currently being used by the advanced chemical and pharmaceutical research industries. It is an aldonic acid with probiotics, antimicrobial, antioxidant, calcium chelating activity. In dairy and food products, it can be used to improve flavor, texture, yield and shelf life with additional health benefits. The biochemical method for producing lactobionic acid makes it safe for humans to consume as food or medicine. This systematic review describes the various bioproduction methods of lactobionic acid. This study emphasizes the production method, conversion rate, and specific yield of various microorganisms and enzymes employed in biosynthesis of lactobionic acid. Scopus advanced search is used for database mining. Original, traceable peer-reviewed research articles directly related to lactobionic acid are selected for this systematic review. The selected articles are grouped for ease of discussion and understanding. In the last 75 years, several bioproduction methods of lactobionic acid have been developed. By fine-tuning the microbial incubation conditions, the productivity of lactobionic acid can be significantly improved. The oxidoreductase enzymes responsible for the conversion of lactose can be purified from the system by advanced membrane technology. In the presence of a suitable redox mediator and regenerative enzyme, an efficient continuous lactobionic acid production system can be developed. To date, several methods are available for the complete conversion of lactose to lactobionic acid with an impressive specific production rate. This review will help researchers and industries to have better insights and understanding of the bioproduction of lactobionic acid.

An assessment of the intact casein content in natural cheddar cheese to determine its suitability in processed cheeses with desired properties.

As compared to age, intact casein in the natural cheddar cheese is a better index of selection for manufacturing processed cheese. In view of this, the present investigation was designed to establish relation between intact casein of the natural cheese with desirable properties of the processed cheese so that the most desirable intact casein in the natural cheddar cheese can be selected on the basis of required properties of the processed cheese. Processed cheese was prepared by using natural cheddar cheese of different intact casein content (ICC) and analysed for meltability, oiling off and hardness. Multiple linear regression was used for prediction of ICC using meltability, oiling off and hardness and it was observed that the all the independent variables significantly affected ICC. Adjusted R2 value of 0.952 and root mean square error of 1.04 suggested a good fit and validation of the developed equation.

NCYM, a Cis-antisense gene of MYCN, encodes a de novo evolved protein that inhibits GSK3ß resulting in the stabilization of MYCN in human neuroblastomas.

The rearrangement of pre-existing genes has long been thought of as the major mode of new gene generation. Recently, de novo gene birth from non-genic DNA was found to be an alternative mechanism to generate novel protein-coding genes. However, its functional role in human disease remains largely unknown. Here we show that NCYM, a cis-antisense gene of the MYCN oncogene, initially thought to be a large non-coding RNA, encodes a de novo evolved protein regulating the pathogenesis of human cancers, particularly neuroblastoma. The NCYM gene is evolutionally conserved only in the taxonomic group containing humans and chimpanzees. In primary human neuroblastomas, NCYM is 100% co-amplified and co-expressed with MYCN, and NCYM mRNA expression is associated with poor clinical outcome. MYCN directly transactivates both NCYM and MYCN mRNA, whereas NCYM stabilizes MYCN protein by inhibiting the activity of GSK3ß, a kinase that promotes MYCN degradation. In contrast to MYCN transgenic mice, neuroblastomas in MYCN/NCYM double transgenic mice were frequently accompanied by distant metastases, behavior reminiscent of human neuroblastomas with MYCN amplification. The NCYM protein also interacts with GSK3ß, thereby stabilizing the MYCN protein in the tumors of the MYCN/NCYM double transgenic mice. Thus, these results suggest that GSK3ß inhibition by NCYM stabilizes the MYCN protein both in vitro and in vivo. Furthermore, the survival of MYCN transgenic mice bearing neuroblastoma was improved by treatment with NVP-BEZ235, a dual PI3K/mTOR inhibitor shown to destabilize MYCN via GSK3ß activation. In contrast, tumors caused in MYCN/NCYM double transgenic mice showed chemo-resistance to the drug. Collectively, our results show that NCYM is the first de novo evolved protein known to act as an oncopromoting factor in human cancer, and suggest that de novo evolved proteins may functionally characterize human disease.

Induction of interleukin-1ß by activated microglia is a prerequisite for immunologically induced fatigue.

We previously reported that an intraperitoneal (i.p.) injection of synthetic double-stranded RNA, polyriboinosinic:polyribocytidylic acid (poly-I:C), produced prolonged fatigue in rats, which might serve as a model for chronic fatigue syndrome. The poly-I:C-induced fatigue was associated with serotonin transporter (5-HTT) overexpression in the prefrontal cortex (PFC), a brain region that has been suggested to be critical for fatigue sensation. In the present study, we demonstrated that microglial activation in the PFC was important for poly-I:C-induced fatigue in rats, as pretreatment with minocycline, an inhibitor of microglial activation, prevented the decrease in running wheel activity. Poly-I:C injection increased the microglial interleukin (IL)-1ß expression in the PFC. An intracerebroventricular (i.c.v.) injection of IL-1ß neutralising antibody limited the poly-I:C-induced decrease in activity, whereas IL-1ß (i.c.v.) reduced the activity in a dose-dependent manner. 5-HTT expression was enhanced by IL-1ß in primary cultured astrocytes but not in microglia. Poly-I:C injection (i.p.) caused an increase in 5-HTT expression in astrocytes in the PFC of the rat, which was inhibited by pretreatment with minocycline (i.p.) and rat recombinant IL-1 receptor antagonist (i.c.v.). Poly-I:C injection (i.p.) led to a breakdown of the blood-brain barrier and enhanced Toll-like receptor 3 signaling in the brain. Furthermore, direct application of poly-I:C enhanced IL-1ß expression in primary microglia. We therefore propose that poly-I:C-induced microglial activation, which may be at least partly caused by a direct action of poly-I:C, enhances IL-1ß expression. Then, IL-1ß induces 5-HTT expression in astrocytes, resulting in the immunologically induced fatigue.

Free distribution of insecticidal bed nets improves possession and preferential use by households and is equitable: findings from two cross-sectional surveys in thirteen malaria endemic districts of Bangladesh.

BACKGROUND: BRAC, an indigenous non-governmental development organization (NGO), has been implementing a programme to prevent and control malaria in the 13 malaria-endemic districts of Bangladesh since 2007. One of the critical preventive interventions is the distribution of insecticidal bed nets (long-lasting insecticide-treated nets, LLINs and insecticide-treated ordinary nets, ITNs) to the community free of cost. This study aimed to assess progress in the possession, preferential use, and knowledge on use of the LLIN/ITNs including the programme's avowed pro-poor inclination one and three and half years after intervention began. METHODS: A convenient sampling strategy based on malaria endemicity in the districts was adopted. First, thirty upazila (sub-district, with a population around 250,000)s were selected at random, with high prevalent districts contributing more upazilas; second, from each upazila, one (2008) to two (2011) villages (covered by insecticidal bed net distribution programme) were selected. From each village, households that had either one under-five child and/or a pregnant woman were included in the survey, one household being included only once. Data were collected using a pre-tested structured questionnaire. RESULTS: In all, 3,760 households in 2008 and 7,895 households in 2011 were surveyed for collecting relevant information. Proportion of households with at least one LLIN, and at least one LLIN/ITN increased (22-59 to 62-67% and 22-64% to 74-76% respectively) over time, including increase in the mean number of LLIN/ITNs per household (≤ 1 to 1 +). The programme achieved > 80% coverage in sleeping under an LLIN/ITN in the case of under-five children and pregnant women, especially in the high-endemic districts. Knowledge regarding critical time of hanging the net also increased over time (7-22 to 44-54%), but remained low. The pro-poor inclination of the programme is reflected in the status of relevant indicators according to self-rated poverty status of the households. CONCLUSIONS: There has been a substantial improvement in possession and usage of insecticidal bed nets especially for the two most vulnerable groups (under-five children and pregnant women), including a reduction of gaps between the high and low endemic districts, and the deficit and non-deficit households during the study period.

COVID-19 Vaccine Hesitancy among Temporary Foreign Workers from Bangladesh.

The COVID-19 pandemic poses an extraordinary threat to the health, safety, and freedom of temporary foreign workers (TFWs). Highly effective vaccines against COVID-19 may hold an outsized benefit for TFWs, particularly those living in congregate settings where protective measures such as social distancing are not possible. While some studies of migrant destination countries have included migrants, no study to date has sought to understand variations in vaccine hesitancy among individuals in a single migrant source population across different destinations. Such a design is critical for understanding how the context of immigration affects levels of hesitancy among migrants from similar conditions of origin. This observational study leverages longitudinal data from an ongoing monthly rapid-response survey of TFWs from Bangladesh (n = 360). Overall vaccine hesitancy was 25%, with significant variation by host country. Multivariate analyses confirmed that immigration system factors and threat perception are the strongest predictors of COVID-19 vaccine hesitancy for TFWs. The predicted probability of hesitancy for an undocumented TFW was 0.405, while the predicted probability for those with valid visas was 0.207 (p < .01). The probability of being hesitant for TFWs who were worried about getting COVID-19 was 0.129 compared to 0.305 (p < .01) for those who were not worried. Results reveal low vaccine hesitancy among TFWs from Bangladesh with differences in location, undocumented status, COVID-19 threat perception, and level of worry about side effects. There could be relatively high returns for targeting vaccine access and distribution to TFWs because of their high levels of vaccine acceptance.

ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma.

Human anaplastic lymphoma kinase (ALK) has been identified as an oncogene that is mutated or amplified in NBLs. To obtain a better understanding of the molecular events associated with ALK in the pathogenesis of NBL, it is necessary to clarify how ALK gene contributes to NBL progression. In the present study, we found that ALK expression was significantly high in NBL clinical samples with amplified MYCN (n = 126, P < 0.01) and in developing tumors of MYCN-transgenic mice. Indeed, promoter analysis revealed that ALK is a direct transcriptional target of MYCN. Overexpression and knockdown of ALK demonstrated its function in cell proliferation, migration and invasion. Moreover, treatment with an ALK inhibitor, TAE-684, efficiently suppressed such biological effects in MYCN amplified cells and tumor growth of the xenograft in mice. Our present findings explore the fundamental understanding of ALK in order to develop novel therapeutic tools by targeting ALK for aggressive NBL treatment.

NLRR1 enhances EGF-mediated MYCN induction in neuroblastoma and accelerates tumor growth in vivo.

Neuronal leucine-rich repeat protein-1 (NLRR1), a type-1 transmembrane protein highly expressed in unfavorable neuroblastoma, is a target gene of MYCN that is predominately expressed in primary neuroblastomas with MYCN amplification. However, the precise biological role of NLRR1 in cell proliferation and tumor progression remains unknown. To investigate its functional importance, we examined the role of NLRR1 in EGF and insulin growth factor-1 (IGF-1)-mediated cell viability. We found that NLRR1 positively regulated cell proliferation through activation of extracellular signal-regulated kinase mediated by EGF and IGF-1. Interestingly, EGF stimulation induced endogenous MYCN expression through Sp1 recruitment to the MYCN promoter region, which was accelerated in NLRR1-expressing cells. The Sp1-binding site was identified on the promoter region for MYCN induction, and phosphorylation of Sp1 was important for EGF-mediated MYCN regulation. In vivo studies confirmed the proliferation-promoting activity of NLRR1 and established an association between NLRR1 expression and poor prognosis in neuroblastoma. Together, our findings indicate that NLRR1 plays an important role in the development of neuroblastoma and therefore may represent an attractive therapeutic target for cancer treatment.