Osteoporosis is one of the most important but often neglected bone disease associated with aging and postmenopausal condition leading to bone loss and fragility. Probiotics have been associated with various immunomodulatory properties and have the potential to ameliorate several inflammatory conditions including osteoporosis. Lactobacillus acidophilus (LA) was selected as probiotic of choice in our present study due its common availability and established immunomodulatory properties. In the present study, we report for the first time that administration of LA in ovariectomized (ovx) mice enhances both trabecular and cortical bone microarchitecture along with increasing the mineral density and heterogeneity of bones. This effect of LA administration is due to its immunomodulatory effect on host immune system. LA thus skews the Treg-Th17 cell balance by inhibiting osteoclastogenic Th17 cells and promoting anti-osteoclastogenic Treg cells in ovx mice. LA administration also suppressed expression of osteoclastogenic factors (IL-6, IL-17, TNF-α and RANKL) and increased expression of anti-osteoclastogenic factors (IL-10, IFN-γ). Taken together the present study for the first time clearly demonstrates the therapeutic potential of LA as an osteo-protective agent in enhancing bone health (via tweaking Treg-Th17 cell balance) in postmenopausal osteoporosis.

Garlic (Allium sativum), a popular food spice and flavoring agent, has also been used traditionally to treat various ailments especially bacterial infections for centuries in various cultures around the world. The principal phytochemicals that exhibit antibacterial activity are oil-soluble organosulfur compounds that include allicin, ajoenes, and allyl sulfides. The organosulfur compounds of garlic exhibit a range of antibacterial properties such as bactericidal, antibiofilm, antitoxin, and anti-quorum sensing activity against a wide range of bacteria including multi-drug resistant (MDR) strains. The reactive organosulfur compounds form disulfide bonds with free sulfhydryl groups of enzymes and compromise the integrity of the bacterial membrane. The World Health Organization (WHO) has recognized the development of antibiotic resistance as a global health concern and emphasizes antibiotic stewardship along with the urgent need to develop novel antibiotics. Multiple antibacterial effects of organosulfur compounds provide an excellent framework to develop them into novel antibiotics. The review provides a focused and comprehensive portrait of the status of garlic and its compounds as antibacterial agents. In addition, the emerging role of new technologies to harness the potential of garlic as a novel antibacterial agent is discussed.

The T box transcription antitermination system is a riboswitch found primarily in Gram-positive bacteria which monitors the aminoacylation of the cognate tRNA and regulates a variety of amino acid-related genes. Novel 4,5-disubstituted oxazolidinones were identified as high affinity RNA molecular effectors that modulate the transcription antitermination function of the T box riboswitch.Identifying RNA ligands that modulate transcription regulation is an important area for drug discovery that has been only minimally explored to date. One potential therapeutic target is the T box transcription antitermination mechanism. This mechanism regulates many amino acid-related genes, including aminoacyl-tRNA synthetase genes, and is found predominantly in Gram-positive bacteria. 1 The T box RNAs are members of the "riboswitch" family in which nascent RNAs directly sense effector molecules to control gene expression. 2-4 The T box genes contain a complex set of structural elements within the 5′ untranslated region of their mRNAs (the "leader region"). These elements include a transcription termination signal that abrogates synthesis of the full-length mRNA and a competing antiterminator element. Readthrough of the terminator, and expression of the downstream gene, is dependent on binding of a specific uncharged tRNA to the nascent RNA transcript; each gene in the T box family responds independently to the cognate uncharged tRNA. 5 The T box antitermination mechanism can function in the absence of additional cellular factors, 6 and the antiterminator RNA element is a critical component of the mechanism. 5 The leader RNA-tRNA interaction stabilizes the antiterminator element, thereby preventing formation of the competing terminator element (Figure 1). The antiterminator element is highly conserved and has been extensively characterized by genetic, biochemical and structural biology approaches. 7-9 A significant challenge in rational ligand design for RNA structure-specific binding is to achieve both high affinity and excellent tertiary structure specificity. Aminoglycosides, the most widely studied RNA ligands, bind primarily in divalent cation binding sites. 10-12 The electrostatic attraction between the multiple protonated amino groups and the negatively charged RNA phosphate backbone leads to very high affinities. However, due to the ubiquitous presence of divalent cation binding sites in RNA, primarily for tertiary fold stabilization, 13 the aminoglycosides readily bind many RNAs 14 thus reducing their utility for RNA structurespecific ligand design. A variety of other RNA ligands have been investigated, 15-21 but few Correspondence to: Jennifer V. Hines. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the produ...

Osteoporosis is associated with reduced density and quality of bone leading to weakened skeleton thereby increasing the risk of fractures responsible for increased morbidity and mortality. Due to preference for western food style the consumption of salt intake in our diets has increased many folds. High dietary salt intake has recently been linked with induction of Th17 cells along with impairment of Treg cells. Also, Th17 cells have been one of major players in the pathophysiology of various bone pathologies including osteoporosis. We thus hypothesized that high salt diet (HSD) intake would lead to enhanced bone loss by modulating Th17-Treg cell balance. In the present study, we report for the first time that HSD intake in male mice impairs both trabecular and cortical bone microarchitecture along with decreasing the mineral density and heterogeneity of bones. The HSD modulates host immune system and skews Treg-Th17 balance by promoting osteoclastogenic Th17 cells and inhibiting development of anti-osteoclastogenic Treg cells in mice. HSD also enhanced expression of proinflammatory cytokines (IL-6, TNF-α, RANKL and IL-17) and decreased the expression of anti-inflammatory cytokines (IL-10, IFN-γ). Taken together the present study for the first time establishes a strong correlation between high dietary salt intake and bone health via interplay between Th17-Treg cells.

Human T-lymphotrophic virus type-1 (HTLV-1) infects approximately 15 to 20 million people worldwide, with endemic areas in Japan, the Caribbean, and Africa. The virus is spread through contact with bodily fluids containing infected cells, most often from mother to child through breast milk or via blood transfusion. After prolonged latency periods, approximately 3 to 5% of HTLV-1 infected individuals will develop either adult T-cell leukemia/lymphoma (ATL), or other lymphocyte-mediated disorders such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The genome of this complex retrovirus contains typical gag, pol, and env genes, but also unique nonstructural proteins encoded from the pX region. These nonstructural genes encode the Tax and Rex regulatory proteins, as well as novel proteins essential for viral spread in vivo such as, p30, p12, p13 and the antisense encoded HBZ. While progress has been made in the understanding of viral determinants of cell transformation and host immune responses, host and viral determinants of HTLV-1 transmission and spread during the early phases of infection are unclear. Improvements in the molecular tools to test these viral determinants in cellular and animal models have provided new insights into the early events of HTLV-1 infection. This review will focus on studies that test HTLV-1 determinants in context to full length infectious clones of the virus providing insights into the mechanisms of transmission and spread of HTLV-1.