B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role.

(1) Aim: Medulloblastoma is the most common aggressive pediatric cancer of the central nervous system. Improved therapies are necessary to improve life outcomes for medulloblastoma patients. Exosomes are a subset of extracellular vesicles that are excreted outside of the cell, and can transport nucleic acids and proteins from donor cells to nearby recipient cells of the same or dissimilar tissues. Few publications exist exploring the role that exosomes play in medulloblastoma pathogenesis. In this study, we found B7-H3, an immunosuppressive immune checkpoint, present in D283 cell-derived exosomes. (2) Methods: Utilizing mass spectrometry and immunoblotting, the presence of B7-H3 in D283 control and B7-H3 overexpressing exosomes was confirmed. Exosomes were isolated by Systems Biosciences from cultured cells as well as with an isolation kit that included ultracentrifugation steps. Overlay experiments were performed to determine mechanistic impact of exosomes on recipient cells by incubating isolated exosomes in serum-free media with target cells. Impact of D283 exosome incubation on endothelial and UW228 medulloblastoma cells was assessed by immunoblotting. Immunocytochemistry was employed to visualize exosome fusion with recipient cells. (3) Results: Overexpressing B7-H3 in D283 cells increases exosomal production and size distribution. Mass spectrometry revealed a host of novel, pathogenic molecules associated with B7-H3 in these exosomes including STAT3, CCL5, MMP9, and PI3K pathway molecules. Additionally, endothelial and UW228 cells incubated with D283-derived B7-H3-overexpressing exosomes induced B7-H3 expression while pSTAT1 levels decreased in UW228 cells. (4) Conclusions: In total, our results reveal a novel role in exosome production and packaging for B7-H3 that may contribute to medulloblastoma progression.

Targeting RGS4 Ablates Glioblastoma Proliferation.

Glioblastoma (GBM) is the most common type of adult primary brain tumor with a median survival rate of less than 15 months, regardless of the current standard of care. Cellular heterogeneity, self-renewal ability and tumorigenic glioma cancer stem cell (GSC) populations contribute to the difficulty in treating GBM. G-protein-coupled receptors (GPCRs) are the largest group of membrane proteins and mediate many cellular responses. Regulators of G-protein signaling 4 (RGS4) are negative regulators of G-protein signaling, and elevated levels of RGS4 are reportedly linked with several human diseases, including cancer. This study investigates the effect of silencing RGS4, resulting in inhibition of GSC growth, invasion and migration. Data obtained from The Cancer Genome Atlas (TCGA) demonstrated poor patient survival with high expression of RGS4. Immunohistochemistry and immunoblot analysis conducted on GBM patient biopsy specimens demonstrated increased RGS4 expression correlative with the TCGA data. RNA sequencing confirmed a significant decrease in the expression of markers involved in GSC invasion and migration, particularly matrix metalloproteinase-2 (MMP2) in knockout of RGS4 using CRISPR plasmid (ko-RGS4)-treated samples compared to parental controls. Gelatin zymography confirmed the reduced activity of MMP2 in ko-RGS4-treated samples. Silencing RGS4 further reduced the invasive and migratory abilities and induction of apoptosis of GSCs as evidenced by Matrigel plug assay, wound healing assay and human apoptosis array. Collectively, our results showed that the silencing of RGS4 plays an important role in regulating multiple cellular functions, and is an important therapeutic target in GBM.

Hand1 overexpression inhibits medulloblastoma metastasis.

Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Current treatment includes surgery, radiation and chemotherapy. However, ongoing treatment in patients is further classified according to the presence or absence of metastasis. Since metastatic medulloblastoma are refractory to current treatments, there is need to identify novel biomarkers that could be used to reduce metastatic potential, and more importantly be targeted therapeutically. Previously, we showed that ionizing radiation-induced uPAR overexpression is associated with increased accumulation of ß-catenin in the nucleus. We further demonstrated that uPAR protein act as cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand1. Among the histological subtypes classical and desmoplastic subtypes account for the majority while large cell/anaplastic variant is most commonly associated with metastatic disease. In this present study using immunohistochemical approach and patient data mining for the first time, we demonstrated that Hand1 expression is observed to be downregulated in all the subtypes of medulloblastoma. Previously we showed that Hand1 overexpression regulated medulloblastoma angiogenesis and here we investigated the role of Hand1 in the context of Epithelial-Mesenchymal Transition (EMT). Moreover, UW228 and D283 cells overexpressing Hand1 demonstrated decreased-expression of mesenchymal markers (N-cadherin, ß-catenin and SOX2); metastatic marker (SMA); and increased expression of epithelial marker (E-cadherin). Strikingly, human pluripotent stem cell antibody array showed that Hand1 overexpression resulted in substantial decrease in pluripotency markers (Nanog, Oct3/4, Otx2, Flk1) suggesting that Hand1 expression may be essential to attenuate the EMT and our findings underscore a novel role for Hand1 in medulloblastoma metastasis.

Targeting DUSPs in glioblastomas - wielding a double-edged sword?

Several dual-specificity phosphatases (DUSPs) that play key roles in the direct or indirect inactivation of different MAP kinases (MAPKs) have been implicated in human cancers over the past decade. This has led to a growing interest in identifying DUSPs and their specific inhibitors for further testing and validation as therapeutic targets in human cancers. However, the lack of understanding of the complex regulatory mechanisms and cross-talks between MAPK signaling pathways, combined with the fact that DUSPs can act as a double-edged sword in cancer progression, calls for a more careful and thorough investigation. Among the various types of brain cancer, glioblastoma multiforme (GBM) is notorious for its aggressiveness and resistance to current treatment modalities. This has led to the search for new molecular targets, particularly those involving various signaling pathways. DUSPs appear to be a promising target, but much more information on DUSP targets and their effects on GBM is needed before potential therapies can be developed, tested, and validated. This review identifies and summarize the specific roles of DUSP1, DUSP4, DUSP6 and DUSP26 that have been implicated in GBM.

Galectin inhibitors and nanoparticles as a novel therapeutic strategy for glioblastoma multiforme.

Over the past two decades, the gold standard of glioblastoma multiforme (GBM) treatment is unchanged and adjunctive therapy has offered little to prolong both quality and quantity of life. To improve pharmacotherapy for GBM, galectins are being studied provided their positive correlation with the malignancy and disease severity. Despite the use of galectin inhibitors and literature displaying the ability of the lectin proteins to decrease tumor burden and decrease mortality within various malignancies, galectin inhibitors have not been studied for GBM therapy. Interestingly, anti-galectin siRNA delivered in nanoparticle capsules, assisting in blood brain barrier penetrance, is well studied for GBM, and has demonstrated a remarkable ability to attenuate both galectin and tumor count. Provided that the two therapies have an analogous anti-galectin effect, it is hypothesized that galectin inhibitors encapsuled within nanoparticles will likely have a similar anti-galectin effect in GBM cells and further correlate to a repressed tumor burden.

PCR and electrospray ionization mass spectrometry for detection of persistent enterococcus faecalis in cerebrospinal fluid following treatment of postoperative ventriculitis.

We describe the use of PCR and electrospray ionization followed by mass spectrometry (PCR/ESI-MS) to evaluate "culture-negative" cerebrospinal fluid (CSF) from a 67-year-old man who developed postoperative bacterial ventriculitis following a suboccipital craniotomy for resection of an ependymoma in the 4th ventricle. CSF samples were obtained on seven occasions, beginning in the operating room at the time of insertion of a right ventriculoperitoneal shunt (VPS) and continuing until his death, 6 weeks later. During the course of the illness, two initial CSF specimens taken before the initiation of antimicrobial treatment were notable for growth of Enterococcus faecalis. Once antimicrobial treatment was initiated, all CSF cultures were negative. PCR/ESI-MS detected genetic evidence of E. faecalis in all CSF samples, but the level of detection (LOD) decreased once antimicrobial treatment was initiated. When our patient returned with symptoms of meningitis 3 days after the completion of antibiotic treatment, CSF cultures remained negative, but PCR/ESI-MS again found genetic evidence for E. faecalis at levels comparable to the pretreatment levels seen initially. This unique case and these findings suggest that determination of CSF LOD by PCR/ESI-MS may be a very sensitive indicator of persistent infection in patients on antibiotic therapy for complex CNS infections and may have relevance for treatment duration and assessment of persistent or recurrent infection at the completion of therapy.

Single-Stage Titanium Mesh Cranioplasty for the Treatment of Depressed Skull Fractures.

BACKGROUND: Historically, depressed skull fractures that warranted surgery were treated in 2 stages: the first stage involved debridement and craniectomy, followed by the second stage of delayed cranioplasty. More recently, single-stage autologous cranioplasty has been proven to be safe. However, there is a paucity of literature regarding single-stage titanium mesh cranioplasty when autologous repair is not possible. METHODS: A retrospective review identified 22 patients who underwent single-stage titanium mesh cranioplasty for the acute treatment of comminuted depressed skull fractures. Fracture location, fracture etiology, timing of surgery, neurologic complications, infection, and cosmetic deformity were recorded. Average follow-up was 9 months. RESULTS: The mean age of the patients was 34 years (range: 3-77); 83% were male. Seventeen (77%) involved the frontal bone, with 7 (32%) involving the frontal sinus. Eighteen (82%) had open defects at presentation. Sixteen (73%) were neurologically normal. Average time from presentation to repair was 11 hours (range: 1-28 hours). There were no neurologic worsening, seizures, or infections postoperatively. Antibiotic prophylaxis was prescribed in 13 cases (57%). One patient required revision surgery for persistent cosmetic deformity. CONCLUSIONS: Autologous cranioplasty for depressed skull fractures is not always possible especially in cases of significant comminution. From our case series, single-stage titanium mesh cranioplasty appears to be a safe option.

Demystifying neuroblastoma malignancy through fractal dimension, entropy, and lacunarity.

PURPOSE: Neuroblastoma is a pediatric solid tumor with a prognosis associated with histology and age of the patient, which are the parameters of the well-established current classification (Shimada classification). Despite the development of new treatment options, the prognosis of high-risk neuroblastoma patients is still poor. Therefore, there is a continuous need to stratify the children suffering from this tumor. A mathematical and computational approach is proposed to enable automatic and precise cancer diagnosis on the histological slide. METHODS: We targeted the complexity of neuroblastoma by calculating its image entropy (S), fractal dimension (FD), and lacunarity (λ) in a combined mathematical code. First, we tested the proposed method for patient-derived glioma images. It allowed distinguishing between normal brain tissue, grade II, and grade III glioma, which harbor different outcomes. RESULTS: In neuroblastoma, our analysis of image's FD, S, and λ combined with a machine learning algorithm automatically predicted tumor malignancy with a receiver operating characteristic curve of 0.82. FD, S, and λ distinguish between neuroblastoma and ganglioneuroma, but they only partially differentiate between the normal samples and the other classes. Ganglioneuroma, the most differentiated form, and poorly-differentiated neuroblastoma display different values of FD, S, and λ. CONCLUSIONS: FD, S, and λ of imaging recognize groups in neuroblastic tumors. We suggest that future studies including these features may challenge the current Shimada classification of neuroblastoma with categories of favorable and unfavorable histology. It is expected that this methodology could trigger multicenter studies and potentially find practical use in the clinical setting of children's hospitals worldwide.

uPAR and cathepsin B downregulation induces apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma.

Cathepsin B and urokinase plasminogen activator receptor (uPAR) are postulated to play key roles in glioma invasion. Calcineurin is one of the key regulators of mitochondrial-dependent apoptosis, but its mechanism is poorly understood. Hence, we studied subcellular localization of calcineurin after transcriptional downregulation of uPAR and cathepsin B in glioma. In the present study, efficient downregulation of uPAR and cathepsin B increased the translocation of calcineurin A from the mitochondria to the cytosol, decreased pBAD (S136) expression and its interaction with 14-3-3ζ and increased the interaction of BAD with Bcl-xl. Co-depletion of uPAR and cathepsin B induced mitochondrial translocation of BAD, activation of caspase 3 as well as PARP and cytochrome c and SMAC release. These effects were inhibited by FK506 (10 µM), a specific inhibitor of calcineurin. Calcineurin A was co-localized and also co-immunoprecipitated with Bcl-2. This interaction decreased with co-depletion of uPAR and cathepsin B and also with Bcl-2 inhibitor, HA 14-1 (20 µg/ml). Altered localization and interaction of calcineurin A with Bcl-2 was also observed in vivo when uPAR and cathepsin B were downregulated. In conclusion, downregulation of uPAR and cathepsin B induced apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma.

Galectin-1 activates carbonic anhydrase IX and modulates glioma metabolism.

Galectins are a family of ß-galactose-specific binding proteins residing within the cytosol or nucleus, with a highly conserved carbohydrate recognition domain across many species. Accumulating evidence shows that Galectin 1 (Gal-1) plays an essential role in cancer, and its expression correlates with tumor aggressiveness and progression. Our preliminary data showed Gal-1 promotes glioma stem cell (GSC) growth via increased Warburg effect. mRNA expression and clinical data were obtained from The Cancer Genome Atlas database. The immunoblot analysis conducted using our cohort of human glioblastoma patient specimens (hGBM), confirmed Gal-1 upregulation in GBM. GC/MS analysis to evaluate the effects of Gal-1 depletion showed elevated levels of α-ketoglutaric acid, and citric acid with a concomitant reduction in lactic acid levels. Using Biolog microplate-1 mitochondrial functional assay, we confirmed that the depletion of Gal-1 increases the expression levels of the enzymes from the TCA cycle, suggesting a reversal of the Warburg phenotype. Manipulation of Gal-1 using RNA interference showed reduced ATP, lactate levels, cell viability, colony-forming abilities, and increased expression levels of genes implicated in the induction of apoptosis. Gal-1 exerts its metabolic role via regulating the expression of carbonic anhydrase IX (CA-IX), a surrogate marker for hypoxia. CA-IX functions downstream to Gal-1, and co-immunoprecipitation experiments along with proximity ligation assays confirm that Gal-1 physically associates with CA-IX to regulate its expression. Further, silencing of Gal-1 in mice models showed reduced tumor burden and increased survival compared to the mice implanted with GSC controls. Further investigation of Gal-1 in GSC progression and metabolic reprogramming is warranted.

Use of balloon-assisted nasal access to augment endoscopic endonasal transsphenoidal approach: illustrative case.

BACKGROUND: Pituitary adenoma is a neurosurgical pathology commonly resected via endoscopic endonasal approach. Septal and nasal passage anatomy can affect the surgical corridor and may require septoplasty or other techniques for expansion. OBSERVATIONS: The authors presented a case of pituitary macroadenoma with septal deviation with use of balloon-assisted nasal access for surgery. LESSONS: This technique enhanced surgical width of field and instrument maneuverability via septal medialization for successful tumor resection.

TERT expression increases with tumor grade in a cohort of IDH-mutant gliomas.

The molecular mechanisms underlying progression from astrocytoma to secondary glioblastoma are poorly understood. Telomerase reverse transcriptase (TERT), a gene encoding for the catalytic subunit of telomerase, is upregulated in various cancers. Upregulation of TERT is a likely mechanism by which malignant cells delay senescence and evade cell death. TERT activity is also the primary mechanism by which malignant cells replenish telomeres, with the other means of telomere replacement being the alternative lengthening of the telomeres (ALT) system. The ALT system is known to be upregulated in tumors harboring loss of function mutations in ATRX. This study analyzed aggregate data on TERT and ATRX expression in astrocytoma, anaplastic astrocytoma, and secondary glioblastoma and then supplemented the data with our findings. In data obtained from Oncomine, significantly higher TERT expression is seen in astrocytomas and secondary glioblastomas compared to normal brain tissue. Additionally, The Cancer Genome Atlas data shows that TERT expression is a significant predictor of overall survival in low-grade gliomas. However, studies comparing the expression of TERT across all grades of astrocytomas had not been performed to date. Using immunohistochemical staining, we showed that controlling for ATRX and IDH mutational status, TERT expression increased with tumor grade in a cohort of patient-derived astrocytoma, anaplastic astrocytoma, and secondary glioblastoma samples. These findings indicate that TERT expression increases as astrocytomas become more aggressive tumors, and probably plays a role in their progression.

Cerebellar glioblastoma: a retrospective review of 21 patients at a single institution.

Primary cerebellar glioblastoma (CGB) comprises only 0.4-3.4% of all intracranial glioblastoma. The impact of surgical resection on survival and the efficacy of adjuvant therapies are uncertain as CGB is underrepresented in most studies. To elucidate prognostic factors we performed a single-institutional review of the largest series to date of CGB. The University of Texas MD Anderson Cancer Center database was reviewed from 1990 to 2010. Twenty-one consecutive patients met criteria for inclusion. The Kaplan-Meier product limit method was used to estimate overall survival (OS) and progression-free survival (PFS); groups were compared using the log-rank statistic. The multivariate Cox proportional hazards models were fitted to examine the association of resection with OS and PFS adjusted for other clinical variables. The median age was 39.9 years, and Karnofsky performance status (KPS) was ≥ 80 in 61.5% of patients. The mean extent of resection for contrast enhancement (EOR-CE) was 93.8% (SD = 10.4%; median = 100%), and the median follow-up was 18.4 months (range 1.5-116.1 months). There was no significant association of EOR with OS or PFS. On univariate analysis the presence of leptomeningeal disease (LMD) was associated with a worse OS (6.1 vs. 24.1 months; P = 0.0001) and PFS (3.3 vs. 9 months; P = 0.019). Patients who had adjuvant chemotherapy (CT) had extended PFS (10.1 vs. 2.8 months; P < 0.0001). Adjustment for the presence of leptomeningeal disease (LMD) tended toward an increased risk of progression (HR = 3.46; 95% confidence interval [CI], 0.83-14.5; P = 0.09) and was associated with a significantly increased risk of death (HR = 15.2; 95% CI, 1.3-180; P = 0.03). Having received adjuvant chemotherapy was associated with a decreased risk of progression (HR = 0.02; 95% CI, 0-0.26; P = 0.003). The presence of LMD is a critical factor in the clinical behavior of CGB resulting in markedly decreased OS and PFS. Adjuvant CT resulted in increased PFS but did not significantly affect OS. This was due to a lack of a sizable cohort who did not receive chemotherapy. Furthermore, three of the CT-naïve patients received CT at first progression. In the context of the high EOR in this study, an OS of 18.4 months was achieved.

Beyond glucose: alternative sources of energy in glioblastoma.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. With a designation of WHO Grade IV, it is also the most lethal primary brain tumor with a median survival of just 15 months. This is often despite aggressive treatment that includes surgical resection, radiation therapy, and chemotherapy. Based on the poor outcomes and prevalence of the tumor, the demand for innovative therapies continues to represent a pressing issue for clinicians and researchers. In terms of therapies targeting metabolism, the prevalence of the Warburg effect has led to a focus on targeting glucose metabolism to halt tumor progression. While glucose is the dominant source of growth substrate in GBM, a number of unique metabolic pathways are exploited in GBM to meet the increased demand for replication and progression. In this review we aim to explore how metabolites from fatty acid oxidation, the urea cycle, the glutamate-glutamine cycle, and one-carbon metabolism are shunted toward energy producing pathways to meet the high energy demand in GBM. We will also explore how the process of autophagy provides a reservoir of nutrients to support viable tumor cells. By so doing, we aim to establish a foundation of implicated metabolic mechanisms supporting growth and tumorigenesis of GBM within the literature. With the sparse number of therapeutic interventions specifically targeting metabolic pathways in GBM, we hope that this review expands further insight into the development of novel treatment modalities.

PAD Inhibitors as a Potential Treatment for SARS-CoV-2 Immunothrombosis.

Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, the virus's dynamicity has resulted in the evolution of various variants, including the delta variant and the more novel mu variant. With a multitude of mutant strains posing as challenges to vaccine efficacy, it is critical that researchers embrace the development of pharmacotherapeutics specific to SARS-CoV-2 pathophysiology. Neutrophil extracellular traps and their constituents, including citrullinated histones, display a linear connection with thrombotic manifestations in COVID-19 patients. Peptidylarginine deiminases (PADs) are a group of enzymes involved in the modification of histone arginine residues by citrullination, allowing for the formation of NETs. PAD inhibitors, specifically PAD-4 inhibitors, offer extensive pharmacotherapeutic potential across a broad range of inflammatory diseases such as COVID-19, through mediating NETs formation. Although numerous PAD-4 inhibitors exist, current literature has not explored the depth of utilizing these inhibitors clinically to treat thrombotic complications in COVID-19 patients. This review article offers the clinical significance of PAD-4 inhibitors in reducing thrombotic complications across various inflammatory disorders like COVID-19 and suggests that these inhibitors may be valuable in treating the origin of SARS-CoV-2 immunothrombosis.

[Retracted] Oncogenic role of p53 is suppressed by si­RNA bicistronic construct of uPA, uPAR and cathepsin­B in meningiomas both in vitro and in vivo.

Following the publication of the above paper, we were contacted by the University of Illinois at Chicago, to request the retraction of the above article. Following a formal institutional investigation, the investigation panel concluded that the images in question had falsifying elements. Regarding the above study, the specific allegations that were investigated were that of falsifying elements of Fig. 1B, bottom panel, columns 2 and 3; Fig. 4A, top panel, columns 4, 5 and 6, and middle panel, columns 1, 2 and 3; and Fig. 7D, row 1, column 1 and row 2, column 1.
Following a review of this paper conducted independently by the Editor of International Journal of Oncology, the Editor concurred with the conclusions of the investigation panel, and therefore the above paper has been retracted from the publication. We also tried to contact the authors, but did not receive a reply. The Editor apologizes to the readership for the inconvenience caused. [the original article was published in International Journal of Oncology 38: 973­983, 2011; DOI: 10.3892/ijo.2011.934]

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Immunopathology of galectin-3: an increasingly promising target in COVID-19.

The pandemic brought on by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has become a global health crisis, with over 22 million confirmed cases and 777,000 fatalities due to coronavirus disease 2019 (COVID-19) reported worldwide. The major cause of fatality in infected patients, now referred to as the "Cytokine Storm Syndrome" (CSS), is a direct result of aberrant immune activation following SARS-CoV2 infection and results in excess release of inflammatory cytokines, such as interleukin (IL)-1, tumor necrosis factor α (TNF-α), and IL-6, by macrophages, monocytes, and dendritic cells. Single cell analysis has also shown significantly elevated levels of galectin 3 (Gal-3) in macrophages, monocytes, and dendritic cells in patients with severe COVID-19 as compared to mild disease. Inhibition of Gal-3 reduces the release of IL-1, IL-6, and TNF-α from macrophages in vitro, and as such may hold promise in reducing the incidence of CSS. In addition, Gal-3 inhibition shows promise in reducing transforming growth factor ß (TGF-ß) mediated pulmonary fibrosis, likely to be a major consequence in survivors of severe COVID-19. Finally, a key domain in the spike protein of SARS-CoV2 has been shown to bind N-acetylneuraminic acid (Neu5Ac), a process that may be essential to cell entry by the virus. This Neu5Ac-binding domain shares striking morphological, sequence, and functional similarities with human Gal-3. Here we provide an updated review of the literature linking Gal-3 to COVID-19 pathogenesis. Dually targeting galectins and the Neu5Ac-binding domain of SARS-CoV2 shows tentative promise in several stages of the disease: preventing viral entry, modulating the host immune response, and reducing the post-infectious incidence of pulmonary fibrosis.

A potential role for Galectin-3 inhibitors in the treatment of COVID-19.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of coronavirus disease 2019 (COVID-19), has been declared a global pandemic by the World Health Organization. With no standard of care for the treatment of COVID-19, there is an urgent need to identify therapies that may be effective in treatment. Recent evidence has implicated the development of cytokine release syndrome as the major cause of fatality in COVID-19 patients, with elevated levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) observed in patients. Galectin-3 (Gal-3) is an animal lectin that has been implicated in the disease process of a variety of inflammatory conditions. Inhibitors of the small molecule Gal-3 have been shown to reduce the levels of both IL-6 and TNF-α in vitro and have shown anti-inflammatory effects in vivo. Additionally, a key domain in the spike protein of ß-coronaviridae, a genus which includes SARS-CoV2, is nearly identical in morphology to human Gal-3. These spike proteins are critical for the virus' entry into host cells. Here we provide a systematic review of the available literature and an impetus for further research on the use of Gal-3 inhibitors in the treatment of COVID-19. Further, we propose a dual mechanism by which Gal-3 inhibition may be beneficial in the treatment of COVID-19, both suppressing the host inflammatory response and impeding viral attachment to host cells.

Human umbilical cord blood stem cells upregulate matrix metalloproteinase-2 in rats after spinal cord injury.

Matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes involved in inflammation, wound healing and other pathological processes after neurological disorders. MMP-2 promotes functional recovery after spinal cord injury (SCI) by regulating the formation of a glial scar. In the present study, we aimed to investigate the expression and/or activity of several MMPs, after SCI and human umbilical cord blood mesenchymal stem cell (hUCB) treatment in rats with a special emphasis on MMP-2. Treatment with hUCB after SCI altered the expression of several MMPs in rats. MMP-2 is upregulated after hUCB treatment in spinal cord injured rats and in spinal neurons injured either with staurosporine or hydrogen peroxide. Further, hUCB induced upregulation of MMP-2 reduced formation of the glial scar at the site of injury along with reduced immunoreactivity to chondroitin sulfate proteoglycans. Blockade of MMP-2 activity in hUCB cocultured injured spinal neurons reduced the protection offered by hUCB which indicated the involvement of MMP-2 in the neuroprotection offered by hUCB. Based on these results, we conclude that hUCB treatment after SCI upregulates MMP-2 levels and reduces the formation of the glial scar thereby creating an environment suitable for endogenous repair mechanisms.