Review: Anti-Oxidant and Anti-Aging Properties of Equol in Prostate Health (BPH)

Benign prostatic hyperplasia (BPH) is the pathological cellular progression of glandular proliferation associated with aging. The primary changes in prostate disorders are mediated by the conversion of the principle androgen, testosterone, to its more potent metabolite, 5α-dihydrotestosterone (5α-DHT). However, recent evidence suggests that estrogen hormonal actions via estrogen receptor subtypes also play an important role in BPH. Current pharmaceutical options for BPH have advantages, limitations and adverse effects. Complementary and Alternative Medicine (CAM) treatments for BPH include botanicals such as polyphenols and isoflavones. Equol is a polyphenolic/isoflavonoid molecule derived from intestinal metabolism, dairy and dietary plant sources. Equol has potent anti-oxidant and anti-aging properties to decrease prostatic irritation and potentially neoplastic growth. It has the unique characteristic to bind specifically 5α-DHT by sequestering 5α-DHT from the androgen receptor (AR), thus decreasing androgen hormone actions to improve prostate health by acting as a selective androgen modulator (SAM). It also has affinity for estrogen related receptor gamma (ERR-γ) and estrogen receptor beta (ER-β) within the prostate that is known to improve male health via selective estrogen receptor modulatory (SERM) activities to decrease inflammation, cellular proliferation and carcinogenesis. The possible clinical efficacy of equol on the symptoms associated with BPH is presented and the reviewed findings suggest that equol may provide a well-tolerated and rapid beneficial therapy for BPH that can be used alone or in combination with current pharmaceutical therapies. The beneficial clinical efficacy of equol observed may be due to the multiple positive biological actions that are not present in current pharmaceutical treatments.

Severe &Moderate BPH Symptoms in Mid-Aged Men Improve with Isoflavonoid-Equol Treatment: Pilot Intervention Study

Benign prostatic hyperplasia (BPH) is the pathological cellular progression of glandular proliferation associated with aging. Current available treatment options for BPH have limitations and various adverse effects. Equol is a polyphenolic/isoflavonoid molecule derived from intestinal metabolism, dairy and dietary plant sources. It has the unique characteristic to bind specifically 5α-dihydrotestosterone (5α-DHT) by sequestering 5α-DHT from the androgen receptor, thus decreasing androgen hormone actions to improve prostate health by acting as a selective androgen modulator (SAM). It also has affinity for estrogen related receptor gamma (ERR-γ) and estrogen receptor beta (ER-β) within the prostate that is known to improve male health via selective estrogen receptor modulatory (SERM) activities to decrease inflammation, cellular proliferation and carcinogenesis. We investigated the possible clinical efficacy of equol on the symptoms associated with benign prostatic hyperplasia (BPH) in this study. Materials and Methods: We performed a pilot intervention study evaluating the effects of low dose oral equol supplement (6 mg, twice a day with meals) for 4 weeks in a total of 18 men (49 - 60 years old) with moderate or severe BPH. Subjects included in the study: gave informed consent, underwent a physical examination and verified their BPH symptoms as measured by the International Prostate Symptom Scores (IPSS) and then were assigned to the moderate or severe BPH groups based upon their total IPSS index. All adverse events were reported. The primary efficacy measure was the IPSS parameters comparing baseline to 2 and 4 week IPSS indices. Blood samples were collected at the baseline and 4th week visits that served as secondary efficacy parameters that included testosterone, 5α-DHT and general blood chemistries along with cardiac and hepatic function panels. Results: Low dose equol positively improved moderate to severe BPH symptoms according to the IPSS indices. In moderately symptomatic men (n = 10) 5 out of 7 of the IPSS parameters significantly improved by 4 weeks of equol treatment. In severely symptomatic men (n = 8) all 7 of the IPSS parameters significantly improved with 4 weeks of equol treatment. There were no significant changes in androgen levels, general blood chemistries or cardiac and hepatic function parameters. Although, 5α-DHT levels declined by 21% in severely symptomatic men (from baseline vs. 4 week values). Conclusion: These findings suggest that equol may provide a well tolerated and rapid beneficial therapy for BPH that can be used alone or in combination with current pharmaceutical therapies. The beneficial clinical efficacy of equol observed in this study may be due to the multiple positive biological actions that are not present in current pharmaceutical treatments.

TK1 Membrane Expression May Play a Role in the Invasion Potential of A549 Lung Cancer Cells

Thymidine kinase 1 (TK1) is a well-studied cancer biomarker. It is commonly found upregulated in the serum of cancer patients, and its levels correlate with stage and grade, disease progression, and prognosis. It has recently been reported that TK1 localizes on the plasma cell membrane of hematological and solid malignancies, and not on the membrane of normal healthy cells, and while on the membrane, TK1 has enzymatic activity. However, the function of TK1 on the surface membrane is not well understood. Here, we hypothesize that it may have a role in tumor invasion and migration. It has been shown that TK1 expression levels positively correlate with epithelia to mesenchymal transition (EMT) markers in patients with breast cancer as they progress from HER2+ to triple negative breast cancer. In this study, we silenced TK1 expression by siRNA and show that TK1’s membrane expression is significantly downregulated at 60 hours post transfection. Using a Matrigel-based quantitative invasion assay, we measured cell invasion potential in cells either expressing or lacking TK1 on their membrane and found that cells that lack TK1 on their membrane exhibit decreased invasion potential. These results suggest that TK1’s presence on the membrane may play a role in invasion and cell migration in cancer.

Ex vivo expansion of hematopoietic stem cells

Ex vivo expansion of hematopoietic stem cells(HSCs) would benefit clinical applications in several aspects, to improve patient survival, utilize cord blood stem cells for adult applications, and selectively propagate stem cell populations after genetic manipulation. In this review we summarize and discuss recent advances in the culture systems of mouse and human HSCs, which include stroma/HSC co-culture, continuous perfusion and fed-batch cultures, and those supplemented with extrinsic ligands, membrane transportable transcription factors, complement components, protein modification enzymes, metabolites, or small molecule chemicals. Some of the expansion systems have been tested in clinical trials. The optimal condition for ex vivo expansion of the primitive and functional human HSCs is still under development. An improved understanding of the mechanisms for HSC cell fate determination and the HSC culture characteristics will guide development of new strategies to overcome difficulties. In the future, development of a combination treatment regimen with agents that enhance self-renewal, block differentiation, and improve homing will be critical. Methods to enhance yields and lower cost during collection and processing should be employed. The employment of an efficient system for ex vivo expansion of HSCs will facilitate the further development of novel strategies for cell and gene therapies including genome editing.

Inhibitory leukocyte immunoglobulin-like receptors in cancer development

Inhibitory leukocyte immunoglobulin-like receptors(LILRB1-5) signal through immunoreceptor tyrosine-based inhibitory motifs(ITIMs) in their intracellular domains and recruit phosphatases protein tyrosine phosphatase, non-receptor type 6(PTPN6, SHP-1), protein tyrosine phosphatase, non-receptor type 6(PTPN6, SHP-2), or Src homology 2 domain containing inositol phosphatase(SHIP) to negatively regulate immune cell activation. These receptors are known to play important regulatory roles in immune and neuronal functions. Recent studies demonstrated that several of these receptors are expressed by cancer cells. Importantly, they may directly regulate development, drug resistance, and relapse of cancer, and the activity of cancer stem cells. Although counterintuitive, these findings are consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system. This review focuses on the ligands, expression pattern, signaling, and function of LILRB family in the context of cancer development. Because inhibition of the signaling of certain LILRBs directly blocks cancer growth and stimulates immunity that may suppress tumorigenesis, but does not disturb normal development, LILRB signaling pathways may represent ideal targets for treating hematological malignancies and perhaps other tumors.