The human microbiome is a rich environment consisting ofbacteria, fungi and other commensal microorganisms of thegut, mucosa and skin. The functional role of the gut microbiomeincludes facilitation in metabolism of macronutrients,maturation of the immune system, and production of pro- oranti-inflammatory signaling molecules and peptides. Theidentification of these resident organisms has brought abouta new understanding of disease processes. Nevertheless,more questions remain regarding the interactions within themicrobiome, its interactions with the host, and its contributionsto the pathophysiology of disease. The purpose of thisreview is to examine the existing medical literature to highlightthe role of the gut microbiome in human health, alsopaying attention to its role in several inflammatory skin diseases,namely atopic dermatitis, psoriasis, and rosacea.

An F-box protein, beta-TrCP recognizes substrate proteins and destabilizes them through ubiquitin-dependent proteolysis. It regulates the stability of diverse proteins and functions as either a tumor suppressor or an oncogene. Although the regulation by beta-TrCP has been widely studied, the regulation of beta-TrCP itself is not well understood yet. In this study, we found that the level of beta-TrCP1 is downregulated by various protein kinase inhibitors in triple-negative breast cancer (TNBC) cells. A PI3K/mTOR inhibitor PI-103 reduced the level of beta-TrCP1 in a wide range of TNBC cells in a proteasome-dependent manner. Concomitantly, the levels of c-Myc and cyclin E were also downregulated by PI-103. PI-103 reduced the phosphorylation of beta-TrCP1 prior to its degradation. In addition, knockdown of beta-TrCP1 inhibited the proliferation of TNBC cells. We further identified that pharmacological inhibition of mTORC2 was sufficient to reduce the beta-TrCP1 and c-Myc levels. These results suggest that mTORC2 regulates the stability of beta-TrCP1 in TNBC cells and targeting beta-TrCP1 is a potential approach to treat human TNBC.
Cell Line, Tumor ; Cell Proliferation ; Cell Survival/drug effects ; Cyclin E/genetics/metabolism ; Dose-Response Relationship, Drug ; Female ; Furans/pharmacology ; Gene Knockdown Techniques ; Humans ; Models, Biological ; Multiprotein Complexes/antagonists & inhibitors ; Phosphatidylinositol 3-Kinases/*antagonists & inhibitors ; Phosphorylation/drug effects ; Protein Kinase Inhibitors/*pharmacology ; Proteolysis/drug effects ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; Pyridines/pharmacology ; Pyrimidines/pharmacology ; TOR Serine-Threonine Kinases/*antagonists & inhibitors ; Triple Negative Breast Neoplasms/genetics/*metabolism ; beta-Transducin Repeat-Containing Proteins/genetics/*metabolism

Among the various sacral fixation techniques used to enhance the strength of fixation, S1 screw placement in the sacrum is the most common method. Ventrolateral S1 screw placement through the sacral ala has been used alone or in combination with a medially-directed screw in the S1 pedicle to enhance pull-out resistance. Although the anatomical safe zone was identified, there is a risk of neurovascular injury particularly when the enhancement of fixation strength requires bicortical purchase. The purpose of this cadaver study is to re-evaluate the previous anatomical safe zone when using an S1 screw laterally directed toward the sacral ala. After dissecting the lateral safe zone of sacral ala in 12 human cadavers, K-wires were intentionally inserted deep into this zone. Each "safe" angle to the center of the safe zone was measured and the degree of risk to neurovascular structures was recorded on the basis of the distance in millimeters from the tips of the penetrating K-wires. The results are as follows: the mean safe angle to the center of the anatomical safe zone was 33.5degrees+/-9.3(20-50). Between 20 and 50 degrees, the range of safe angle was too wide. The distance between the tip of the K-wire and the sacroiliac joint, lumbosacral trunk, obturator nerve was 4.8mm+/-1(4-7.5), 6.8mm+/-1(6-9.5) and 6.8mm+/-3.2(0-10) respectively, while the anterior height between sacral cortex and lumbosacral trunk, internal iliac vein was 0mm and 2.1mm+/-1.8(0-5) respectively. In 29% of cases, the iliolumbar artery, the first branch of the internal iliac artery, abnormally crossed the middle of the safe zone. The sacroiliac joint, lumbosacral trunk, internal iliac vein and iliolumbar artery were at risk from laterally-directed S1 screws. This study shows that bicortical placement of S1 screws into the sacral ala presents unnecessary risks to neurovascular structures. It is concluded that the previous anatomical safe zone for bicortical S1 screw placement into the sacral ala was not surgically safe, and when lumbosacral fixation surgery is planned, operative techniques other than bicortical screw placement should be considered.
Arteries ; Cadaver ; Humans ; Iliac Artery ; Iliac Vein ; Intention ; Obturator Nerve ; Sacroiliac Joint ; Sacrum

PURPOSE: To measure the hypermethylation of four genes in primary tumors and paired plasma samples to determine the feasibility of gene promoter hypermethylation markers for detecting breast cancer in the plasma. MATERIALS AND METHODS: DNA was extracted from the tumor tissues and peripheral blood plasma of 34 patients with invasive breast cancer, and the samples examined for aberrant hypermethylation in cyclin D2, retinoic acid receptor beta (RARbeta), twist and high in normal-1 (HIN-1) genes using methylation-specific PCR (MSP), and the results correlated with the clinicopathological parameters. RESULTS: Promoter hypermethylation was detected at high frequency in the primary tumors for cyclin D2 (53%), RARbeta (56%), twist (41%) and HIN-1 (77%). Thirty-three of the 34 (97%) primary tumors displayed promoter hypermethylation in at least one of the genes examined. The corresponding plasma samples showed hyperme thylation of the same genes, although at lower frequencies (6% for cyclin D2, 16% for RARbeta, 36% for twist, and 54% for HIN-1). Overall, 22 of the 33 (67%) primary tumors with hypermethylation of at least one of the four genes also had abnormally hypermethylated DNA in their matched plasma samples. No significant relationship was recognized between any of the clinical or pathological parameters (tumor size, axillary lymph node metastasis, stage, or Ki-67 labeling index) with the frequency of hypermethylated DNA in the primary tumor or plasma. CONCLUSION: The detection of aberrant promoter hypermethylation of cancer-related genes in the plasma may be a useful tool for the detection of breast cancer.
Breast Neoplasms* ; Breast* ; Cyclin D2 ; DNA ; Humans ; Lymph Nodes ; Methylation ; Neoplasm Metastasis ; Plasma* ; Polymerase Chain Reaction ; Receptors, Retinoic Acid

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a positive-sense singlestranded RNA (+ssRNA) that causes coronavirus disease 2019 (COVID-19). The viral genome encodes twelve genes for viral replication and infection. The third open reading frame is the spike (S) gene that encodes for the spike glycoprotein interacting with specific cell surface receptor – angiotensin converting enzyme 2 (ACE2) – on the host cell membrane. Most recent studies identified a single point mutation in S gene. A single point mutation in S gene leading to an amino acid substitution at codon 614 from an aspartic acid 614 into glycine (D614G) resulted in greater infectivity compared to the wild type SARS-CoV2. We were interested in investigating the mutation region of S gene of SARS-CoV2 from Korean COVID-19 patients. New mutation sites were found in the critical receptor binding domain (RBD) of S gene, which is adjacent to the aforementioned D614G mutation residue. This specific sequence data demonstrated the active progression of SARS-CoV2 by mutations in the RBD of S gene.The sequence information of new mutations is critical to the development of recombinant SARS-CoV2 spike antigens, which may be required to improve and advance the strategy against a wide range of possible SARS-CoV2 mutations.