The Pathology of Methanogenic Archaea in Human Gastrointestinal Tract Disease

Methane-producing archaea have recently been associated with disorders of the gastrointestinal tract and dysbiosis of the resident microbiota. Some of these conditions include inflammatory bowel disease (Crohn’s disease (CD) and ulcerative colitis (UC)), chronic constipation, small intestinal bacterial overgrowth, gastrointestinal cancer, anorexia, and obesity. The causal relationship and the putative mechanism by which archaea may be associated with human disease are poorly understood, as are the strategies to alter methanogen populations in humans. It is estimated that 30–62% of humans produce methane detectable in exhaled breath and in the gastrointestinal tract. However, it is not yet known what portion of the human population have detectable methanogenic archaea. Hydrogen and methane are often measured in the breath as clinical indicators of intolerance to lactose and other carbohydrates. Breath gas analysis is also employed to diagnose suspected small intestinal bacterial overgrowth and irritable bowel syndrome, although standards are lacking. The diagnostic value for breath gas measurement in human disease is evolving; therefore, standardized breath gas measurements combined with ever-improving molecular methodologies could provide novel strategies to prevent, diagnose, or manage numerous colonic disorders. In cases where methanogens are potentially pathogenic, more data are required to develop therapeutic antimicrobials or other mitigation strategies

Photodynamic inactivation of Klebsiella pneumoniae biofilms and planktonic cells by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester

The treatment of Klebsiella pneumoniae, particularly extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae, is currently a great challenge. Photodynamic antimicrobial chemotherapy is a promising approach for killing antibiotic-resistant bacteria. The aim of this study was to evaluate the capacity of 5-aminolevulinic acid (5-ALA) and its derivative 5-ALA methyl ester (MAL) in the presence of white light to cause photodynamic inactivation (PDI) of K. pneumoniae planktonic and biofilm cells. In the presence of white light, 5-ALA and MAL inactivated planktonic cells in a concentration-dependent manner. Biofilms were also sensitive to 5-ALA and MAL-mediated PDI. The mechanisms by which 5-ALA and MAL caused PDI of ESBL-producing K. pneumonia were also investigated. Exposure of K. pneumonia to light in the presence of either 5-ALA or MAL induced cleavage of genomic DNA and the rapid release of intracellular biopolymers. Intensely denatured cytoplasmic contents and aggregated ribosomes were also detected by transmission electron microscopy. Scanning electron microscopy showed that PDI of biofilms caused aggregated bacteria to detach and that the bacterial cell envelope was damaged. This study provides insights into 5-ALA and MAL-mediated PDI of ESBL-producing K. pneumoniae

Boronic Acid Derivatives Targeting HIV-1

A series of novel boronic acid derivatives containing either a pyrimidine or purine base was synthesized. The preparation involved the condensation of 4-bromobutyl boronic acid with the appropriate base. These acyclic nucleosides were designed as potential antiviral agents especially targeting the human immunodeficiency virus. Two analogues, 6-chloro-9-(4-dihydroxyborylbutyl)purine and 2,6-dichloro-9-(4-dihydroxyborylbutyl)purine, exhibited EC50 values of 7.7 µM and 0.99 µM, respectively, in an HIV-1 syncytial plaque reduction assay

Experiences of newly diagnosed oral cancer patients during the first wave of the COVID-19 pandemic: A qualitative study from Pakistan

The COVID-19 pandemic has resulted in the scaling back or postponement of non-emergency hospital services, including care of cancer patients. The present qualitative study explored the experiences of newly diagnosed oral cancer patients during the first wave of the COVID-19 pandemic in Pakistan. Patients who attended the Department of Maxillofacial Surgery, Khyber College of Dentistry in July 2020 were selected using a maximum variation purposive sampling method. Seventeen semi-structured interviews were conducted in Pashto, the local language of Khyber Pakhtunkhwa. All interviews were audiotaped, transcribed verbatim, and translated into English. Thematic content analysis yielded eight major themes: pain and generalised physical weakness, shock at diagnosis, psychological distress of the COVID-19 pandemic, faith and religion, double hit loss of employment, social isolation, social support from caregivers, and lack of support from health care professionals. In conclusion, the COVID-19 pandemic has a clear impact on the life experiences of newly diagnosed oral cancer patients. Distress due to delay in accessing health care and lack of support from health care providers are a matter of great concern. Appropriate interventions should be introduced to ensure psychological and social support strategies are in place for patients during interruptions of health care services

Cellular Models of Aggregation-Dependent Template-Directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer's Disease

Copyright © 2015, The American Society for Biochemistry and Molecular Biology. Acknowledgements-We thank Drs Timo Rager and Rolf Hilfiker (Solvias, Switzerland) for polymorph analyses.Peer reviewedPublisher PD

Steamed broccoli sprouts alleviate DSS-induced inflammation and retain gut microbial biogeography in mice

Inflammatory bowel diseases (IBDs) are devastating conditions of the gastrointestinal tract with limited treatments, and dietary intervention may be effective and affordable for managing symptoms. Glucosinolate compounds are highly concentrated in broccoli sprouts, especially glucoraphanin (GLR), and can be metabolized by certain mammalian gut bacteria into antiinflammatory isothiocyanates, such as sulforaphane. Gut microbiota exhibit biogeographic patterns, but it is unknown if colitis alters these or whether the location of glucoraphanin-metabolizing bacteria affects antiinflammatory benefits. We fed specific pathogen-free C57BL/6 mice either a control diet or a 10% steamed broccoli sprout diet and gave a three-cycle regimen of 2.5% dextran sodium sulfate (DSS) in drinking water over a 34-day experiment to simulate chronic, relapsing ulcerative colitis (UC). We monitored body weight, fecal characteristics, lipocalin, serum cytokines, and bacterial communities from the luminal- and mucosal-associated populations in the jejunum, cecum, and colon. Mice fed the broccoli sprout diet with DSS treatment performed better than mice fed the control diet with DSS, and had significantly more weight gain, lower Disease Activity Index scores, lower plasma lipocalin and proinflammatory cytokines, and higher bacterial richness in all gut locations. Bacterial communities were assorted by gut location but were more homogenous across locations in the control diet + DSS mice. Importantly, our results showed that broccoli sprout feeding abrogated the effects of DSS on gut microbiota, as bacterial richness and biogeography were similar between mice receiving broccoli sprouts with and without DSS. Collectively, these results support the protective effect of steamed broccoli sprouts against dysbiosis and colitis induced by DSS

Conductive Carbon Microfibers Derived from Wet-Spun Lignin/Nanocellulose Hydrogels

We introduce an eco-friendly process to dramatically simplify carbon microfiber fabrication from biobased materials. The microfibers are first produced by wet-spinning in aqueous calcium chloride solution, which provides rapid coagulation of the hydrogel precursors comprising wood-derived lignin and 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO)-oxidized cellulose nanofibrils (TOCNF). The thermomechanical performance of the obtained lignin/TOCNF filaments is investigated as a function of cellulose nanofibril orientation (wide angle X-ray scattering (WAXS)), morphology (scanning electron microscopy (SEM)), and density. Following direct carbonization of the filaments at 900 degrees C, carbon microfibers (CMFs) are obtained with remarkably high yield, up to 41%, at lignin loadings of 70 wt % in the precursor microfibers (compared to 23% yield for those produced in the absence of lignin). Without any thermal stabilization or graphitization steps, the morphology, strength, and flexibility of the CMFs are retained to a large degree compared to those of the respective precursors. The electrical conductivity of the CMFs reach values as high as 103 S cm(-1), making them suitable for microelectrodes, fiber-shaped supercapacitors, and wearable electronics. Overall, the cellulose nanofibrils act as structural elements for fast, inexpensive, and environmentally sound wet-spinning while lignin endows CMFs with high carbon yield and electrical conductivity

Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease

Crohn’s disease (CD) is a presentation of inflammatory bowel disease (IBD) that manifests in childhood and adolescence and involves chronic and severe enterocolitis, immune and gut microbial dysregulation, and other complications. Diet and gut-microbiota-produced metabolites are sources of anti-inflammatories that could ameliorate symptoms. However, questions remain on how IBD influences biogeographic patterns of microbial location and function in the gut, how early life transitional gut communities are affected by IBD and diet interventions, and how disruption to biogeography alters disease mediation by diet components or microbial metabolites. Many studies on diet and IBD use a chemically induced ulcerative colitis model, despite the availability of an immune-modulated CD model. Interleukin-10-knockout (IL-10-KO) mice on a C57BL/6 background, beginning at age 4 or 7 weeks, were fed a control diet or one containing 10% (wt/wt) raw broccoli sprouts, which was high in the sprout-sourced anti-inflammatory sulforaphane. Diets began 7 days prior to, and for 2 weeks after inoculation with Helicobacter hepaticus, which triggers Crohn’s-like symptoms in these immune-impaired mice. The broccoli sprout diet increased sulforaphane in plasma; decreased weight stagnation, fecal blood, and diarrhea associated; and increased microbiota richness in the gut, especially in younger mice. Sprout diets resulted in some anatomically specific bacteria in younger mice and reduced the prevalence and abundance of pathobiont bacteria which trigger inflammation in the IL-10-KO mouse, for example, Escherichia coli and Helicobacter. Overall, the IL-10-KO mouse model is responsive to a raw broccoli sprout diet and represents an opportunity for more diet-host-microbiome research

Self-compacting geopolymer concrete with spend garnet as sand replacement

Garnets being the waste spin-off of surface treatment operations remain a major environmental concern worldwide. Robust engineering properties of these waste garnets offer the opportunity to get efficient construction materials via their appropriate recycling. In this spirit, we evaluate the capacity of spent garnets as sand replacement for achieving self-compacting geopolymer concrete (SCGPC). Such SCGPC specimens are prepared using ground granulated blast furnace slag (GGBFS) wherein the river sand is replaced by spent garnet at varying contents (0–100%) under constant Liquid/Binder (L/B) mass ratio of 0.4. Performance evaluations of the developed SCGPC samples are made using several tests including durability, workability, flexural, compressive, splitting tensile strength conforming the EFNARC standard. Test results revealed an enhancement in the workability of the proposed SCGPC specimen with the increase of spent garnet contents. Furthermore, other strengths are discerned to be lower compared to the control sample at all stages of replacement. It is established that the spent garnet is prospective candidate for sand replacement up to 25% in terms of environmental amiability, cost effectiveness and conservation of natural resources

Framing the discussion of microorganisms as a facet of social equity in human health

What do “microbes” have to do with social equity? These microorganisms are integral to our health, that of our natural environment, and even the “health” of the environments we build. The loss, gain, and retention of microorganisms—their flow between humans and the environment—can greatly impact our health. It is well-known that inequalities in access to perinatal care, healthy foods, quality housing, and the natural environment can create and arise from social inequality. Here, we focus on the argument that access to beneficial microorganisms is a facet of public health, and health inequality may be compounded by inequitable microbial exposure