Michael C Velarde

University of the Philippines | UPD · Institute of Biology

Metastasis is a systemic condition and the major challenge among cancer types, as it can lead to multiorgan vulnerability. Recently, attention has been drawn to cellular senescence, a complex stress response condition, as a factor implicated in metastatic dissemination and outgrowth. Here, we examine the current knowledge of the features required f...

Certain bacteria possess the ability to reduce anxiety- and stress-related behaviors through the gut microbiome-brain axis. Such bacteria are called psychobiotics, and can be used to improve mood and cognition. However, only a few bacteria have been characterized as psychobiotics, and their exact mechanism of action remains unclear. Hence, in this...

Metastasis is a systemic condition and the major challenge among cancer types, as it can lead to multiorgan vulnerability. Recently, attention has been drawn to cellular senescence, a complex stress response condition, as a factor implicated in metastatic dissemination and outgrowth. Here, we examine the current knowledge of the features required f...

With recent initiatives to ban bisphenol A (BPA) in certain commercial products, manufacturers shifted to the production and use of BPA analogues. However, some of these BPA alternatives still possess endocrine disruptive activities. Many fungal enzymes are known to biodegrade phenolic compounds, such as BPA. However, the activity of these enzymes...

BACKGROUND Advanced maternal age is associated with decreased oocyte quantity and quality as well as uterine and placental dysfunctions. These changes lead to infertility, pregnancy complications and birth defects in the offspring. As the mean age of giving birth is increasing worldwide, prevention of age-associated infertility and pregnancy compli...

Wound healing is impaired with advanced age and certain chronic conditions, such as diabetes and obesity. Moreover, common cancer treatments, including chemotherapy and radiation, can cause unintended tissue damage and impair wound healing. Available wound care treatments are not always effective, as some wounds fail to heal or recur after treatmen...

Several studies have reported exposure of humans to various endocrine disrupting chemicals (EDCs) worldwide. However, there is a lack of data regarding EDC exposures in humans living in Southeast Asian countries, such as the Philippines. Hence, this study measured levels of 41 EDCs in women residing in the Greater Manila Area, home to the second la...

The occurrence of per- and polyfluoroalkyl substances (PFAS) in water resources is an emerging concern because of their environmental persistence and bioaccumulation in humans. In Western countries, health advisories regarding PFAS exposure have been released to warn the public of its potential adverse effects. However, awareness regarding PFAS exp...

Purpose of Review Cellular senescence is implicated in aging and age-related diseases. Because mitochondrial stress is one of the triggers of cellular senescence, and senescence leads to the accumulation of abnormal mitochondria with impaired dynamics and hampered homeostasis, this review focuses on the therapeutic potential of targeting mitochondr...

High amount of copper is toxic to most organisms, but endophytic fungi can develop survival strategies to tolerate and respond to environmental stressors such as heavy metal contaminants. While high copper induces oxidative stress, it is still unclear which genes are associated with copper tolerance. Here, we performed a metatranscriptome analysis...

Metformin (MET) constitutes the first-line treatment against type 2 diabetes. Growing evidence linking insulin resistance and cancer risk has expanded the therapeutic potential of MET to several cancer types. However, the oncostatic mechanisms of MET are not well understood. MET has been shown to promote the expression of progesterone receptor (PGR...

The chemotherapy drug doxorubicin (DOX) is effective in treating many types of cancers. However, due to its pro-inflammatory and cardiotoxic side effects, other remedies have also been explored as alternative treatments. The plant Alangium longiflorum was reported to contain cytotoxic activity against cancer cells, but it is unclear whether this pl...

Cellular senescence entails an irreversible growth arrest that evolved in part to prevent cancer. Paradoxically, senescent cells secrete proinflammatory and growth-stimulatory molecules, termed the senescence-associated secretory phenotype (SASP), which is correlated with cancer cell proliferation in culture and xenograft models. However, at what t...

Breast cancer (BCa) is the leading cause of female cancer-related death worldwide. Luminal BCa accounts for at least 70% of all BCa and is characterized by its hormone dependence, particularly to estrogen. Endocrine disruptors may function to exert the pro-tumorigenic effects of estrogen in proxy following environmental exposure. Bisphenol A (BPA)...

Biobanking has become an indispensable tool for translational research and health innovations. While the field of biobanking has progressed and evolved globally, biobanking in developing Association of Southeast Asian Nations (ASEAN) countries such as the Philippines remains underrepresented because of several challenges often encountered in these...

Legumes are extensively cultivated around the globe for human consumption and may contain potential estrogenic activities that interfere with normal physiology and pathophysiology. However, different cultivars grown in different regions of the world have different activities that may provide different nutritional value. Hence, in this study, legume...

Renieramycin M (RM) is a KCN-stabilized tetrahydroisoquinoline purified from the blue sponge Xestospongia sp., with nanomolar IC50s against several cancer cell lines. Our goal is to evaluate its combination effects with doxorubicin (DOX) in estrogen receptor positive MCF-7 breast cancer cells. MCF-7 cells were treated simultaneously or sequentially...

Rapamycin, an inhibitor of mechanistic Target Of Rapamycin Complex 1 (mTORC1), extends lifespan and shows strong potential for the treatment of age-related diseases. However, rapamycin exerts metabolic and immunological side effects mediated by off-target inhibition of a second mTOR-containing complex, mTOR complex 2. Here, we report the identifica...

Milkfish is a major finfish product of the Philippines. But because the whole genome sequence of milkfish is still unknown, it is difficult to study the different molecular pathways involved in milkfish after bacterial exposure. Here, transcriptomic analyses by next-generation sequencing (NGS) were used to identify gene expression in milkfish liver...

Milkfish (Chanos chanos Forsskal) is an important aquaculture product and is the sole extant species of the family Chanidae (order Gonorynchiformes). While there are already several reports regarding milkfish aquaculture, studies on milkfish immunity and gene expression are very limited. In this study, we showed that Aeromonas hydrophila induces in...

Squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer, and has a high rate of recurrence and metastasis. Systemic genotoxic chemotherapeutic drugs such as doxorubicin (Doxo) can be used to treat SCC, but these agents can have deleterious long-term side effects, including fueling the development of more aggressive cancers....

Endometriosis is a chronic inflammatory condition that may cause pelvic pain, dysmenorrhea, and/or infertility in women of reproductive age. While treatments may include medical or surgical management, the majority of therapeutic options are non-curative, and women may experience longstanding pain and/or disability. In general, chronic diseases are...

Skin provides barrier protection for the body, but aging disrupts epidermal barrier function. Hu et al. show that disruption of the epidermal barrier increases serum cytokine levels partly because of increased cytokine production by the skin. They then show that restoring epidermal barrier function in aged mice reduces circulating levels of proinfl...

Successful pregnancy is regulated by several soluble factors that are differentially expressed throughout gestation. These factors are important to initiate and establish embryo implantation and parturition. Senescent cells, which undergo permanent cell proliferation arrest in response to stress, also produce several secreted factors, referred to a...

Cellular senescence is a phenomenon occurring when cells are no longer able to divide even after treatment with growth stimuli. Because senescent cells are typically associated with aging and age-related diseases, cellular senescence is hypothesized to contribute to the age-related decline in reproductive function. However, some data suggest that s...

Senescent cells are induced by a wide variety of stimuli. They accumulate in several tissues during aging, including the skin. Senescent cells secrete proinflammatory cytokines, chemokines, growth factors, and proteases, a phenomenon called senescence-associated secretory phenotype (SASP), which are thought to contribute to the functional decline o...

Aging is associated with the onset of several diseases in various organ systems; however, different tissues may age differently, rendering some of them dysfunctional sooner than others. Placental membranes (fetal amniochorionic membranes) protect the fetus throughout pregnancy, but their longevity is limited to the duration of pregnancy. The age-as...

Cellular senescence permanently arrests cell proliferation, often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). Loss of mitochondrial function can drive age-related declines in the function of many post-mitotic tissues, but little is known about how mitochondrial dysfunction affects mitotic tissues. We show here t...

Significance Mitochondrial damage can accelerate features of aging, including impaired tissue regeneration, but little is known about how aging and this damage interact to impair tissue renewal. We show that mitochondrial oxidative stress in the epidermis alters wound healing depending on age. Epidermal mitochondrial damage accelerated wound closur...

Krüppel-like factor (KLF) 13 and the closely-related KLF9 are members of the Sp/KLF family of transcription factors that have collectively emerged as essential regulators of tissue development, differentiation, proliferation, and programmed cell death. Steroid hormone-responsive tissues express multiple KLFs which are linked to progesterone recepto...

Human and mouse skin accumulate senescent cells in both the epidermis and dermis during aging. When chronically present, senescent cells are thought to enhance the age-dependent deterioration of the skin during extrinsic and intrinsic aging. However, when transiently present, senescent cells promote optimal wound healing. Here, we review recent stu...

Cellular senescence is a process that results from a variety of stresses, leading to a state of irreversible growth arrest. Senescent cells accumulate during aging and have been implicated in promoting a variety of age-related diseases. Mitochondrial stress is an effective inducer of cellular senescence, but the mechanisms by which mitochondria reg...

Decline in circulating sex steroid hormones accompanies several age-associated pathologies which may influence human healthspan. Mitochondria play important roles in biosynthesis of sex steroid hormones, and these hormones can also regulate mitochondrial function. Understanding the cross talk between mitochondria and sex steroid hormones may provid...

to the editor: This letter is a response to the commentary by Drs. Ralph J. Turner and Irwin J. Kerber ([7][1]) regarding my review article ([8][2]) in Physiological Genomics . I thank Drs. Turner and Kerber for their interest and encouraging remarks on the review article. I applaud their enthusiasm

Cancer is a devastating disease that increases exponentially with age. Cancer arises from cells that proliferate in an unregulated manner, an attribute that is countered by cellular senescence. Cellular senescence is a potent tumor-suppressive process that halts the proliferation, essentially irreversibly, of cells at risk for malignant transformat...

Estrogen provides many beneficial effects early in life by regulating normal tissue development and several physiological functions. While estrogen replacement therapy (ERT) in women was expected to rescue the health risks associated with the age-related decline in estrogen levels during menopause, ERT also resulted in increased progression to othe...

Endometriosis is characterized by progesterone resistance and associated with infertility. Krüppel-like factor 9 (KLF9) is a progesterone receptor (PGR)-interacting protein, and mice null for Klf9 are subfertile. Whether loss of KLF9 expression contributes to progesterone resistance of eutopic endometrium of women with endometriosis is unknown. The...

Cellular senescence arrests the proliferation of mammalian cells at risk for neoplastic transformation, and is also associated with aging. However, the factors that cause cellular senescence during aging are unclear. Excessive reactive oxygen species (ROS) have been shown to cause cellular senescence in culture, and accumulated molecular damage due...

Cellular senescence in human keratinocytes and skin fibroblasts treated with rotenone (A) Proliferation (number of population doubling in 4 days) of primary human skin fibroblasts (HCA2, green) and keratinocytes (AG21837, blue) treated with various doses of rotenone for 4 days. (B) Quantitation of the percentage of HCA2 and AG21837 cells with posit...

Inappropriate early exposure of the hormone-responsive uterus to estrogenic compounds is associated with increased risk for adult reproductive diseases including endometrial cancers. While the dysregulation of estrogen receptor-alpha (ESR1) signaling is well acknowledged to mediate early events in tumor initiation, mechanisms contributing to sustai...

Progesterone plays an important role in regulating multiple events in the uterus. It controls endometrial proliferation and differentiation, which are important for uterine function. Dysregulation of progesterone signaling leads to impaired physiological functions. Indeed, aberrant expression of progesterone-regulated genes in the endometrium has b...

Krüppel-like factors (KLFs), of which there are currently 17 known protein members, belong to the specificity protein (Sp) family of transcription factors and are characterized by the presence of Cys(2)/His(2) zinc finger motifs in their carboxy-terminal domains that confer preferential binding to GC/GT-rich sequences in gene promoter and enhancer...

Endometriosis is characterized by endometrial tissue growth outside the uterus, due primarily to survival, proliferation, and neoangiogenesis of eutopic endometrial cells and fragments refluxed into the peritoneal cavity during menses. Although various signaling molecules, including cAMP, regulate endometrial proliferation, survival, and embryonic...

Endometriosis is an estrogen-dependent disorder primarily associated with pelvic pain and infertility in up to 10% of women of reproductive age. Recent studies suggest that resistance to progesterone action may contribute to the development and pathophysiology of this disorder. In this study we examined the in vivo and in vitro expression and funct...

Estrogen, acting through its cognate receptor estrogen receptor-alpha (ESR1), is a critical regulator of uterine endometrial epithelial proliferation. Although the dynamic communication between endometrial stromal (ST) and epithelial cells is considered to be an important component in this process, key molecular players in particular compartments r...

Preterm and delayed labor conditions are devastating health problems with currently unknown etiologies. We previously showed that the transcription factor Krüppel-like factor 9 (KLF9) influences the expression and/or transcriptional activity of receptors for estrogen and progesterone in endometrial cells in vivo and in vitro. Given that estrogen an...

Estrogen and progesterone, acting through their respective receptors and other nuclear proteins, exhibit opposing activities in target cells. We previously reported that Krüppel-like factor 9 (KLF9) cooperates with progesterone receptor (PR) to facilitate P-dependent gene transcription in uterine epithelial cells. Here we evaluated whether KLF9 may...

The uterine endometrium undergoes dynamic changes in proliferation and differentiation in response to estrogen (E) and progesterone (P) during the estrous cycle and pregnancy. E and P exert their functions through their respective nuclear receptors, estrogen receptor (ESR) and progesterone receptor (PGR), which interact with specific nuclear protei...

The etiologies of pre-term and delayed labor are not well-understood and have been ascribed in part to uterine dysfunction. Clinical conditions of premature and delayed labor, with 8–12% frequencies in the United States, result in perinatal mortality and morbidity, with attendant significant emotional, social, and economic burdens. Given the ethica...

Krüppel-like factor 9 (Klf9), a zinc-finger transcription factor, is implicated in the control of cell proliferation, cell differentiation, and cell fate. Using Klf9-null mutant mice, we have investigated the involvement of Klf9 in intestine crypt-villus cell renewal and lineage determination. We report the predominant expression of Klf9 gene in sm...

Progesterone receptor (PR), a ligand-inducible transcription factor, mediates the physiological actions of progesterone (P) through two distinct isoforms, PR-A and PR-B, and numerous nuclear coregulators. We previously demonstrated that basic transcription element binding protein-1 (BTEB1), a transcription factor of the Krüppel-like family, is a fu...

Dietary soy intake is associated with protection from breast cancer, but questions persist on the potential risks of the major soy isoflavone genistein (GEN) on female reproductive health. Here, we evaluated intermediate markers of cancer risk in uteri of cycling, young adult Sprague-Dawley rats lifetime exposed to one of three AIN-93G semipurified...

Female mice null for the basic transcription element binding protein-1 (Bteb1) gene have reduced numbers of implanting embryos. We hypothesized that the implantation defect, resulting in subfertility, is a consequence of developmental asynchrony between the embryo and uterine endometrium at peri-implantation. To address this, endometrium from wild-...

We previously demonstrated that female Sprague-Dawley rats fed AIN-93G diets containing soy protein isolate (SPI+) had lower DMBA-induced mammary tumor incidence than those fed diets containing casein (CAS), due partly to altered Phase I metabolism with soy. Here, we evaluated the tumor protective effects of these same diets to the direct-acting ca...

The over-expression of epidermal growth factor receptor (EGFR) and its ligands, epidermal growth factor (EGF) and transforming growth factor-alpha, is a common feature of epithelial carcinomas and correlates with neoplastic progression. Secretory leukocyte protease inhibitor (SLPI), a member of the Kazal superfamily of serine anti-proteases, induce...

We have found that AIN-93G diets made with whey protein hydrolysate (WPH) reduce 7,12-dimethyl-benz[a]anthracene (DMBA)-induced tumor incidence in Sprague-Dawley (Harlan) rats relative to those fed a diet with casein (CAS). Herein, we replicated these findings in another Sprague-Dawley substrain (Charles River) and examined whether WPH protective e...