Alcohol is the most socially accepted addictive drug. Alcohol consumption is associated with some health problems such as neurological, cognitive, behavioral deficits, cancer, heart and liver disease. Mechanisms of alcohol-induced toxicity are presently not yet clear. One of the mechanisms underlying alcohol toxicity has to do with its interaction with amino acid-homocysteine (Hcy), which has been linked with brain neurotoxicity. Elevated homocysteine (Hcy) impairs with various physiological mechanisms in the body, especially metabolic pathways. Hcy metabolism is predominantly controlled by epigenetic regulation such as DNA methylation, histone modifications, and acetylation. An alteration in these processes leads to epigenetic modification. Therefore, in this review, we summarize the role of Hcy metabolism abnormalities in alcohol-induced toxicity with epigenetic adaptation and their influences on cerebrovascular pathology.

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition characterized by painful nodules which suppurate and later develop into scar tissues followed by the development of hypodermal tracts. Although the mechanisms behind HS are not fully understood, it is known that dietary factors play important roles in flare frequency and severity. We hypothesize that the high fat diet (HFD) causes dysbiosis, systemic inflammation, and hyperhomocysteinemia (HHcy) in susceptible individuals, which subsequently elevate inflammatory cytokines such as IL-1β, IL-6, IL-17, and tumor necrosis factor alpha (TNF-α). This increase in dysbiosis-led inflammation coupled with a dysregulation of the 1-carbon metabolism results in an increase in matrix metalloproteinases MMP-2, MMP-8, and MMP-9 along with tissue matrix remodeling in the development and maintenance of the lesions and tracts. This manuscript weaves together the potential roles played by the gut microbiome, HHcy, MMPs, and the 1-carbon metabolism toward HS disease causation in susceptible individuals.

Periodontal disease is one of the most common conditions resulting from poor oral hygiene and is characterized by a destructive process in the periodontium which essentially include gingiva, alveolar mucosa, cementum, periodontal ligament, and the alveolar bone. Notably, the destructive event in the alveolar bone has been linked to homocysteine (Hcy) metabolism however; it has not yet been fully investigated. Therefore; the implication of Hcy towards initiation, progression, and maintenance of the periodontal disease remains incompletely understood. Our research has led to the discovery that hyperhomocysteinemia (HHcy) causes changes in the periodontal tissues as well as it leads to an increase in the angiogenesis‐related proteins, potentially indicating a faster onset of periodontal disease in the susceptible individuals. To study periodontal tissue status and angiogenesis‐related protein levels, we compared wild‐type C57BL/6J (WT) and CBS+/− (HHcy) mice strains. The distance between cementoenamel junction, and the alveolar bone crest (CEJ‐BC) were measured histomorphometrically using histological preparations (Hematoxylin and Eosin; H&E, and the Masson’s Trichrome staining). Serum angiogenesis‐related levels namely the angiogenin, angiopoietin‐1, endostatin/collagen XVIII, FGF acid, IGFBP‐1, IGFBP‐2, MMP‐9 (pro and active forms), PDGF‐AA, PDGF‐AB/PDGF‐BB, pentraxin‐3 were measured using the Proteome ProfilerTM Array Kit specific for the mouse. The data suggest an increase in the distance between cementoenamel junction, and the alveolar bone crest. Levels of the angiogenesis‐related proteins in CBS+/− mouse strain were also significantly increased in comparison to the WT control mice. Interestingly, some of these angiogenesis‐related proteins have been shown to be upregulated during the periodontal disease. Our findings thus underscore the importance of Hcy metabolism towards the loss of periodontal tissue homeostasis, and the causation of the periodontal disease indicating that regulating Hcy metabolism can help prevent periodontal tissue damage, and the periodontal disease in people who suffer from chronic metabolic disorders such as hyperhomocysteinemia. Support or Funding Information Funding from the National Institutes of Health (NIH): HL139047, AR071789, HL74815, HL107640, HL139047, and DK116591.

Hidradenitis Suppurativa (HS) is a chronic inflammatory condition about which little is known. HS results from occlusion of the apocrine sweat glands of the skin. The blocked follicles will become inflamed, swell, and burst, leaving scar tissue after lesional skin heals. As the disease progresses, tracts develop beneath the skin, which connect lesional areas to new regions. MMP activity is elevated in lesional, perilesional, and tract biopsies. Obesity is known to exacerbate the condition, while the mechanism is unknown. A High Fat Diet (HFD) causes gut dysbiosis and we hypothesize that this shift in the microbiome leads to an increase in circulating inflammatory cytokines and inflammation in the mammary gland (MG), a modified apocrine gland. Mice fed a HFD showed elevated inflammatory cytokines in serum and MG tissue. MMP activity was increased in mice fed a HFD compared to normal diet (ND), but was mitigated when given probiotic (PB). MMP inhibitors such as TIMP‐3 were significantly over expressed in the HFD+PB group. Administration of probiotic and restoration of the gut microflora has a protective effect against inflammation caused by a HFD. Support or Funding Information Research supported by NIH grants HL74185, HL139047, and AR‐71789.

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