Gut matters in microgravity: potential link of gut microbiota and its metabolites to cardiovascular and musculoskeletal well-being.

The gut microbiota and its secreted metabolites play a significant role in cardiovascular and musculoskeletal health and diseases. The dysregulation of the intestinal microbiota poses a significant threat to cardiovascular and skeletal muscle well-being. Nonetheless, the precise molecular mechanisms underlying these changes remain unclear. Furthermore, microgravity presents several challenges to cardiovascular and musculoskeletal health compromising muscle strength, endothelial dysfunction, and metabolic changes. The purpose of this review is to critically examine the role of gut microbiota metabolites on cardiovascular and skeletal muscle functions and dysfunctions. It also explores the molecular mechanisms that drive microgravity-induced deconditioning in both cardiovascular and skeletal muscle. Key findings in this review highlight that several alterations in gut microbiota and secreted metabolites in microgravity mirror characteristics seen in cardiovascular and skeletal muscle diseases. Those alterations include increased levels of Firmicutes/Bacteroidetes (F/B) ratio, elevated lipopolysaccharide levels (LPS), increased in para-cresol (p-cresol) and secondary metabolites, along with reduction in bile acids and Akkermansia muciniphila bacteria. Highlighting the potential, modulating gut microbiota in microgravity conditions could play a significant role in mitigating cardiovascular and skeletal muscle diseases not only during space flight but also in prolonged bed rest scenarios here on Earth.

Serum multi-omics analysis in hindlimb unloading mice model: Insights into systemic molecular changes and potential diagnostic and therapeutic biomarkers.

Microgravity, in space travel and prolonged bed rest conditions, induces cardiovascular deconditioning along with skeletal muscle mass loss and weakness. The findings of microgravity research may also aid in the understanding and treatment of human health conditions on Earth such as muscle atrophy, and cardiovascular diseases. Due to the paucity of biomarkers and the unknown underlying mechanisms of cardiovascular and skeletal muscle deconditioning in these environments, there are insufficient diagnostic and preventative measures. In this study, we employed hindlimb unloading (HU) mouse model, which mimics astronauts in space and bedridden patients, to first evaluate cardiovascular and skeletal muscle function, followed by proteomics and metabolomics LC-MS/MS-based analysis using serum samples. Three weeks of unloading caused changes in the function of the cardiovascular system in c57/Bl6 mice, as seen by a decrease in mean arterial pressure and heart weight. Unloading for three weeks also changed skeletal muscle function, causing a loss in grip strength in HU mice and atrophy of skeletal muscle indicated by a reduction in muscle mass. These modifications were partially reversed by a two-week recovery period of reloading condition, emphasizing the significance of the recovery process. Proteomics analysis revealed 12 dysregulated proteins among the groups, such as phospholipid transfer protein, Carbonic anhydrase 3, Parvalbumin alpha, Major urinary protein 20 (Mup20), Thrombospondin-1, and Apolipoprotein C-IV. On the other hand, metabolomics analysis showed altered metabolites among the groups such as inosine, hypoxanthine, xanthosine, sphinganine, l-valine, 3,4-Dihydroxyphenylglycol, and l-Glutamic acid. The joint data analysis revealed that HU conditions mainly impacted pathways such as ABC transporters, complement and coagulation cascades, nitrogen metabolism, and purine metabolism. Overall, our results indicate that microgravity environment induces significant alterations in the function, proteins, and metabolites of these mice. These observations suggest the potential utilization of these proteins and metabolites as novel biomarkers for assessing and mitigating cardiovascular and skeletal muscle deconditioning associated with such conditions.

Unveiling the molecular Culprit of arterial stiffness in vitamin D deficiency and obesity: Potential for novel therapeutic targets.

Cardiovascular diseases (CVDs) are highly associated with both vitamin D deficiency and obesity, two prevalent health conditions worldwide. Arterial stiffness, an independent predictor of CVDs, is particularly elevated in both conditions, yet the molecular mechanisms underlying this phenomenon remain elusive, hindering effective management of CVDs in this population. We recruited 20 middle-aged Emiratis, including 9 individuals with vitamin D deficiency (Vit D level ≤20 ng) and obesity (BMI ≥30) and 11 individuals as control with Vit D level >20 ng and BMI <30. We measured arterial stiffness using pulse wave velocity (PWV) and performed whole transcriptome sequencing to identify differentially expressed genes (DEGs) and enriched pathways. We validated these findings using qRT-PCR, Western blot, and multiplex analysis. PWV was significantly higher in the vitamin D deficient and obese group relative to controls (p ≤ 0.05). The DEG analysis revealed that pathways related to interleukin 1 (IL-1), nitrogen metabolism, HIF-1 signaling, and MAPK signaling were over-activated in the vitamin D deficient and obese group. We found that HIF-1alpha, NOX-I, NOX-II, IL-1b, IL-8, IL-10, and VEGF were significantly upregulated in the vitamin D deficient and obese group (p < 0.05). Our study provides new insights into the molecular mechanisms of arterial stiffness in vitamin D deficiency and obesity, demonstrating the role of oxidative stress and inflammation in this process. Our findings suggest that these biomarkers may serve as potential therapeutic targets for early prevention of CVDs. Further studies are needed to investigate these pathways and biomarkers with larger cohort.

Efficacy of prostaglandin E2 versus prostaglandin F2 alpha assisted with narrowband-UVB in stable vitiligo.

In the recent decades, prostaglandins were recommended as a new therapeutic modality of stable vitiligo with promising efficacy. Therefore, we designed the current work to compare the significance of two different subtypes of prostaglandins [prostaglandin E2 (PGE2) versus prostaglandin F2 alpha (PGF2α)], assisted with NB-UVB phototherapy, in treatment of stable vitiligo. This study was conducted on 30 patients with stable non-segmental vitiligo. Three approximately similar vitiliginous areas were chosen in each patient and assigned into 3 groups. Each group treated with intradermal injection of either PGE2 (group I), PGF2α (group II), or saline as placebo (group III) at frequency once/week for 12 weeks. Concomitantly, all groups received NB-UVB phototherapy twice weekly for 3 months. The outcomes of this study discovered that the therapeutic efficacy of intradermal injection of either PGE2 or PGF2α assisted with NB-UVB phototherapy was comparable with non-significant difference between them in spite of being significantly higher than NB-UVB alone. However, there were a significantly earlier onset of repigmentation and higher degree of satisfaction regarding areas treated with PGE2 than those treated with PGF2α. In conclusion, both PGF2α and PGE2 intradermal injection could be considered as quite simple and affordable techniques in the treatment of stable vitiligo with no reported side effects and good patient satisfaction.

Comparison of Various Diagnostic Techniques for the Detection of Blastocystis Spp. and its Molecular Characterisation in Farm Animals in the United Arab Emirates.

Introduction: Blastocystis spp. is a common anaerobic intestinal parasite infecting humans and a diverse range of animals. The aim of the study was to compare different diagnostic methods for the detection of Blastocystis and survey the occurrence of its subtypes in farm animals, namely sheep, cows and camels, in Al-Ain, United Arab Emirates. Material and Methods: Ninety-seven faecal samples comprised of 69 from sheep, 12 from cows and 16 from camels were submitted to DNA extraction, PCR and sequencing. Blastocystis was screened for microscopically in 65 samples using direct wet-mount, modified acid-fast staining, trichrome staining and in vitro culture techniques. Results: Fifteen (15.5%) samples were positive by PCR, twelve of which were confirmed by sequencing. Using PCR as a comparison standard, the sensitivity and specificity of the direct wet-mount, modified acid-fast staining, trichrome staining and in vitro culture methods were 40.0% and 78.3%, 40.0% and 83.3%, 80.0% and 80.0%, and 80.0% and 76.7% respectively. Only culture and trichrome tests were significantly associated with PCR (odds ratio (OR) = 13.14; 95% confidence interval (CI): 1.35-127.4; P = 0.007 and OR = 16; 95% CI: 1.63-156.5; P = 0.003, respectively) with trichrome detecting more positive cases than in vitro culture. The subtype (ST)10 was the only one found in all 12 sequenced sheep isolates. Conclusion: The study corroborated previous data indicating that sheep are the natural hosts for ST10. No zoonotic subtypes nor mixed-subtype colonisation were found. The report also confirmed the superiority of trichrome staining in detecting Blastocystis spp.

Circulating microRNAs as potential biomarkers of early vascular damage in vitamin D deficiency, obese, and diabetic patients.

Vitamin D3 deficiency, obesity, and diabetes mellitus (DM) have been shown to increase the risk of cardiovascular diseases (CVDs). However, the early detection of vascular damage in those patients is still difficult to ascertain. MicroRNAs (miRNAs) are recognized to play a critical role in initiation and pathogenesis of vascular dysfunction. Herein, we aimed to identify circulating miRNA biomarkers of vascular dysfunction as early predictors of CVDs. We have recruited 23 middle-aged Emiratis patients with the following criteria: A healthy control group with vitamin D ≥ 20ng, and BMI < 30 (C1 group = 11 individuals); A vitamin D deficiency (Vit D level ≤ 20 ng) and obese (BMI ≥ 30) group (A1 group = 9 patients); A vitamin D deficiency, obese, plus DM (A2 group = 3 patients). Arterial stiffness via pulse wave velocity (PWV) was measured and the whole transcriptome analysis with qPCR validation for miRNA in plasma samples were tested. PWV relative to age was significantly higher in A1 group 19.4 ± 4.7 m/s and A2 group 18.3 ± 1.3 m/s compared to controls 14.7 ± 2.1 m/s (p < 0.05). Similar patterns were also observed in the Augmentation pressure (AP) and Alx%. Whole RNA-Sequencing revealed miR-182-5p; miR-199a-5p; miR-193a-5p; and miR-155-5p were differentially over-expressed (logFC > 1.5) in high-risk patients for CVDs vs healthy controls. Collectively, our result indicates that four specific circulating miRNA signature, may be utilized as non-invasive, diagnostic and prognostic biomarkers for early vascular damage in patients suffering from vitamin D deficiency, obesity and DM.

Three-Dimensional Collagen Topology Shapes Cell Morphology, beyond Stiffness.

Cellular heterogeneity is associated with many physiological processes, including pathological ones, such as morphogenesis and tumorigenesis. The extracellular matrix (ECM) is a key player in the generation of cellular heterogeneity. Advances in our understanding rely on our ability to provide relevant in vitro models. This requires obtainment of the characteristics of the tissues that are essential for controlling cell fate. To do this, we must consider the diversity of tissues, the diversity of physiological contexts, and the constant remodeling of the ECM along these processes. To this aim, we have fabricated a library of ECM models for reproducing the scaffold of connective tissues and the basement membrane by using different biofabrication routes based on the electrospinning and drop casting of biopolymers from the ECM. Using a combination of electron microscopy, multiphoton imaging, and AFM nanoindentation, we show that we can vary independently protein composition, topology, and stiffness of ECM models. This in turns allows one to generate the in vivo complexity of the phenotypic landscape of ovarian cancer cells. We show that, while this phenotypic shift cannot be directly correlated with a unique ECM feature, the three-dimensional collagen fibril topology patterns cell shape, beyond protein composition and stiffness of the ECM. On this line, this work is a further step toward the development of ECM models recapitulating the constantly remodeled environment that cells face and thus provides new insights for cancer model engineering and drug testing.

Strengthening Public Health Scholarship in Sudan: The Role of Leadership and Mentorship Development.

A robust public health workforce in Sudan is essential for accelerating progress toward the Sustainable Development Goals, and strengthening public health education is a priority for the Ministries of Health and Higher Education. Faculty at public health training institutions are a critical resource. Globally, development programs for junior to midlevel public health faculty have been well documented. However, most involved direct partnership between a university from the Global North and only one or two universities from the Global South, only one included an explicit focus on creation of a leadership network, and none were launched as fully virtual collaborations. Therefore, we conducted a mixed-method evaluation of the fully virtual Yale-Sudan Program for Research Leadership in Public Health. We used program records, participant feedback, competency assessment, and network analysis to evaluate 1) participant engagement, 2) change in skill, and 3) change in collaboration. The program achieved a 93% graduation rate. All participants would "definitely" recommend the program and described the live virtual sessions as engaging, effective, and accessible. We observed progress toward learning objectives and significant increases in 13 of 14 leadership and mentorship competency domains. Collaboration across Sudanese institutions increased, including an almost doubling in the number of pairs reporting scholarly collaboration. Eight authorship teams are actively working toward peer-reviewed publications. The program engaged scholars and policymakers from across Sudan and the Sudanese diaspora achieved high levels of co-creation and continues despite significant political unrest in the country, serving as a promising model for strengthening of public health education in Sudan.

Hindlimb unloading induces time-dependent disruption of testicular histology in mice.

Mechanical unloading of the body in the hindlimb unloaded (HU) mice induces pathology in multiple organs, but the effects on testes are poorly characterized. We investigated the histology and Raman spectroscopy of the mouse testes following HU condition. We divided male, c57BL/6j mice into ground-based controls or experimental groups for two and four weeks of HU. The testes tissues were dissected after euthanasia to investigate histological and Raman spectroscopic analysis. We found an HU-induced atrophy of testes irrespective of the time duration (p < 0.05). Histological analysis revealed that the HU induced epithelial thinning, luminal widening, and spermatozoa decline in the seminiferous tubules of the mouse testes. In addition, we found a thickening of the epididymal epithelia and tunica albuginea. These changes were accompanied by a generalized depression in the Raman spectra, indicating an altered concentration and/or orientation of several molecules. We also report reduced signal intensities of hydroxyproline and tryptophan, potentially contributing to testicular pathology during HU. Taken together, our findings indicate that the two or four weeks of HU induce disruption of testicular architecture and molecular phenotypes. Our results may have implications for understanding and/or treating male infertility associated with prolonged bed rest and spaceflight.

Suppression of endoplasmic reticulum stress prevents disuse muscle atrophy in a mouse model of microgravity.

BACKGROUND: Hind-limb unloaded (HLU) mouse model exhibits skeletal muscle atrophy and weakness mimicking the conditions such as prolonged spaceflight. However, the molecular mechanisms and interventions of muscle loss during muscle unloading remain elusive. Dysfunction of protein folding by ednoplasmic reticulum (ER), a condition called ER stress, is implicated in diseases of various cell types, but its contribution to skeletal muscle detriment remains elusive. In this study, we investigated the contribution of ER stress to muscle atrophy. METHODS: Sixteen-week-old c57BL/6j male mice were grouped into ground-based controls and HLU group, which was subsequently injected with injected saline (HLU-sal.) or pan-ER stress inhibitor 4-PBA (100mg/kg/d; HLU- 4PBA) via intraperitoneal injections for three weeks. RESULTS: Three weeks of HLU resulted in reduction in muscle mass and strength, which were restored with 4PBA injections. We also report myofibers atrophy, myonuclear apoptosis, and aterations in the expressions of genes associated with ER stress, apoptosis, and calcium dysregulation. These findings were reversed by 4-PBA treatment. CONCLUSION: Altogether, our results indicate that ER stress contributes to muscle atrophy in HLU conditions. We suggest that blocking ER stress may be an effective pharmacological therapy to prevent muscle weakness and atrophy during prolonged muscle unloading.

Mitigating sarcoplasmic reticulum stress limits disuse-induced muscle loss in hindlimb unloaded mice.

Muscle disuse in the hindlimb unloaded (HU) mice causes significant atrophy and weakness. However, the cellular and molecular mechanisms driving disuse-muscle atrophy remain elusive. We investigated the potential contribution of proteins dysregulation by sarcoplasmic reticulum (SR), a condition called SR stress, to muscle loss during HU. Male, c57BL/6j mice were assigned to ground-based controls or HU groups treated with vehicle or 4-phenylbutyrate (4-PBA), a potent inhibitor of SR stress, once a day for three weeks. We report that the 4-PBA reduced the SR stress and partly reversed the muscle atrophy and weakness in the HU mice. Transcriptome analysis revealed that several genes were switched on (n = 3688) or differentially expressed (n = 1184) due to HU. GO, and KEGG term analysis revealed alterations in pathways associated with the assembly of cilia and microtubules, extracellular matrix proteins regulation, calcium homeostasis, and immune modulation during HU. The muscle restoration with 4-PBA partly reversed these changes along with differential and unique expression of several genes. The analysis of genes among the two comparisons (HU-v vs. control and HU-t vs. HU-v.) shows 841 genes were overlapped between the two comparisons and they may be regulated by 4-PBA. Altogether, our findings suggest that the pharmacological suppression of SR stress may be an effective strategy to prevent disuse-induced muscle weakness and atrophy.

Synergistic Anti-Angiogenic Effect of Combined VEGFR Kinase Inhibitors, Lenvatinib, and Regorafenib: A Therapeutic Potential for Breast Cancer.

Background: Breast cancer currently affects more than two million women worldwide, and its incidence is steadily increasing. One of the most essential factors of invasion and metastasis of breast cancer cells is angiogenesis and non-angiogenic vascularization. Lenvatinib and Regorafenib share the same anti-angiogenic effect by inhibiting vascular endothelial growth factor receptors (VEGFRs subtypes 1 to 3) and have been approved for treating different types of cancer. Methods: We investigated Lenvatinib and Regorafenib effects on a well-established in-vitro model of breast cancer using MCF-7 (estrogen, progesterone receptor-positive, and HER2-negative), MDA-MB-231 (triple negative), as well as Human Umbilical Vascular Endothelial Cell line (HUVEC) cell lines. We performed the cell viability assay on four groups of cells, which included a control group, a Lenvatinib treated only group, a Regorafenib treated only group, and a group treated with a combination of both drugs at 24, 48, and 72 h. Data were analyzed as means ± standard deviation, and the drug−drug interactions with Compusyn software. Cellular migration assay, tube formation assay, and Western blots were conducted to determine the functional and the protein expression of downstream signals such as Caspase-9, anti-apoptotic Survivin, P-ERK, and total-ERK in the control and treatment groups. Results: MCF-7 cells showed a reduction in cell survival rates with higher dosing and longer incubation periods with each drug and with the combination of drugs. A synergistic interaction was identified (CI < 1) with both drugs on MCF7 at different dose combinations and at a higher dose in MDA-MB-231 cells. Furthermore, there was a marked decrease in the anti-angiogenic effect of both drugs in tube formation assay using MDA-MB-231 cells and survivin protein expression in MCF-7, and those antitumor markers showed a better outcome in drug combination than the use of each drug alone. Conclusion: Our result is the first to report the synergistic anti-angiogenic potential of combination therapy of Lenvatinib and Regorafenib. Therefore, it shows their therapeutic potential in breast cancer, including the aggressive types. Further studies are warranted to confirm and explore this therapeutic approach.

Spontaneous Splenic Rupture in Malaria Patients: Two Case Reports.

Atraumatic splenic rupture is a rare and life-threatening condition, if not diagnosed. We present two cases with a history of travel to endemic areas, who came to the emergency department with abdominal pain and were diagnosed to have spontaneous splenic rupture as a complication of severe malaria. Both patients were treated surgically by splenectomy. A high level of clinical suspicion is critical in every malaria patient presenting with abdominal pain, even if it is mild. Clinical imaging modalities like ultrasonography and computed tomography (CT) are crucial diagnostic tools in managing such patients.

Evaluation of the effect of combined intralesional injection of prostaglandin F2α with narrow band UVB phototherapy in treatment of resistant cases of vitiligo.

BACKGROUND: Vitiligo is a chronic cutaneous disease characterized with hypopigmented patches that leave psychological impact on the patients. There is increasing need for new treatment modalities to shorten the duration of treatment of vitiligo with the least side effects. OBJECTIVE: To explore the effect of intralesional injection of prostaglandin F2α on the outcome of narrow band ultraviolet rays B (NBUVB) for patients with stable vitiligo. PATIENTS AND METHODS: The study included 27 stable vitiligo patients with overall symmetrical lesions. For each patient, one patch was treated with NBUVB alone (control side), while another symmetrical patch was treated with combined intralesional injection of prostaglandin F2α with NBUVB therapy, weekly for 3 months. RESULTS: There was statistically significant improvement in the repigmentation in the combination group compared with NBUVB group. Side effects were minimal. CONCLUSION: Intralesional injection of prostaglandin F2α in combination with NBUVB therapy could be considered as safe and tolerable technique for treatment of vitiligo, it shortens the duration of NBUVB therapy. Longer follow up is needed.

Rifampicin-Induced Pneumonitis Mimicking Severe COVID-19 Pneumonia Infection.

BACKGROUND Rifampicin-induced pneumonitis is an infrequent occurrence, with only a few cases reported in the literature. Furthermore, this condition constitutes a diagnostic challenge, particularly in the era of COVID-19 infection. Here, we report a case of rifampicin-induced pneumonitis with clinical, imaging, and histological features of acute respiratory distress syndrome (ARDS), which required severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to exclude a diagnosis of coronavirus disease 2019 (COVID-19) pneumonia. CASE REPORT A 43-year-old man on anti-TB treatment for TB meningitis developed new-onset fever, fatigue, hypoxemic respiratory failure, and bilateral pulmonary opacities. His clinical, chest X-ray, and CT thorax findings of ARDS were similar to both rifampicin-induced pneumonitis and severe COVID-19 pneumonia. However, reverse transcription polymerase chain reaction (RT-PCR) testing from a nasopharyngeal swab and bronchoalveolar lavage (BAL) via the GeneXpert system was negative for SARS-CoV-2. A detailed workup, including lung biopsy, revealed drug-induced pneumonitis as the cause of his presentation. His pneumonitis improved after discontinuation of rifampicin and recurred following the rifampicin challenge. CONCLUSIONS This case highlights the importance of early, rapid, and accurate testing for SARS-CoV-2 during the COVID-19 pandemic for patients presenting with acute respiratory symptoms, so that accurate diagnosis and early patient management are not delayed for patients with treatable causes of acute and severe lung diseases. Timely identification of rifampicin-induced pneumonitis via a high clinical suspicion, detailed workup, and histopathological analysis is required to avoid permanent damage to the lungs.

Cinnamic acid nanoparticles modulate redox signal and inflammatory response in gamma irradiated rats suffering from acute pancreatitis.

Acute Pancreatitis (AP) is a multifactorial disease. It was characterized by severe inflammation and acinar cell destruction. Thus, the present study was initiated to evaluate the role the of Cinnamic acid nanoparticles (CA-NPs) as a modulator for the redox signaling pathway involved in the development of pancreatitis. AP in rats was induced by L-arginine and exposure to gamma radiation. The pancreatic injury was evaluated using biochemical and histological parameters. Upon the oral administration of CA-NPs, both the severity of acute pancreatitis and the serum levels of amylase and lipase were decreased. Furthermore, the malondialdehyde (MDA) levels of the pancreatic tissue were significantly reduced and the depletion of glutathione was considerably restored. The injury and apoptosis of pancreatic tissues were markedly improved by the reduction of the caspase-3 levels. Additionally, the alleviation of pancreatic oxidative damage by CA-NPs was accompanied by a down-regulation of the NLRP3, NF-κB, and ASK1/MAPK signaling pathways. Collectively, the current findings showed that CA-NPs could protect the pancreatic acinar cell from injury not only by its antioxidant, anti-inflammatory effect but also by modulation of the redox-sensitive signal transduction pathways contributed to acute pancreatitis severity. Accordingly, cinnamic acid nanoparticles have therapeutic potential for the management of acute pancreatitis.

Intestinal Parasite Detection in Assorted Vegetables in the United Arab Emirates.

OBJECTIVES: Consuming raw vegetables presents a considerable risk to the public and is the chief mode of transmission of intestinal parasites. We sought to assess the degree of parasitic contaminations on selected vegetables in the UAE. METHODS: A total of 218 fresh vegetable samples were collected randomly from different farms and local supermarkets between February 2017 and January 2018. After washing and centrifugation, the sediment was examined microscopically for parasitic forms. RESULTS: Protozoa cysts and helminths eggs were detected in 15.1% (33/218) of samples. The most detected parasites were Entamoeba complex (E. histolytica/E. dispar/E. moshkovskii) (30.3%), Entamoeba coli (18.2%), Trichuris trichiura (12.1%), Strongyloides stercoralis (12.1%), Ascaris lumbricoides egg (9.1%), Endolimax nana cyst and Enterobius vermicularis egg (6.1% each), and Giardia lamblia and Hymenolepis nana (3.0% each). We found no significant association between the vegetable type and the parasite occurrence (p > 0.050). Moreover, parasite incidence was independent of the vegetable type (p > 0.050). CONCLUSIONS: The study highlights the potential of raw produce serving as a major source of foodborne disease outbreaks and its role in the transmission of intestinal parasitic infections. Public education on the safe handling of raw vegetables is recommended.

Immunohistochemical Expression of Calmodulin in Cutaneous Lichen Planus: A Case-Control Study.

BACKGROUND: Calmodulin (CaM) is a multifunctional intermediate messenger protein that plays important role in cell motility, proliferation, and apoptosis. Therefore, it is thought to be involved in various ways in the apoptotic processes which are implicated in the pathogenesis of lichen planus. OBJECTIVE: The aim of this study was to evaluate the immunohistochemical expression of CaM in lichen planus lesions in comparison to normal control skin to throw light on its possible role in disease pathogenesis. PATIENTS AND METHODS: This case-control study was conducted on 50 patients with lichen planus, in addition to 20 age- and sex-matched healthy individuals. Skin biopsy specimens were taken from lesional skin of lichen planus patients as well as normal skin of controls. All were examined for immunohistochemical expression of CaM antibody. RESULTS: There was statistically significant increase of the immunohistochemical expression of CaM in lesional skin of lichen planus patients compared with normal skin of controls (Chi-square test, P < 0.001). No significant correlation could be detected between CaM expression in lesional skin and the studied clinical parameters of lichen planus patients. LIMITATIONS: Tha main limitation of this study is its small sample size. CONCLUSION: CaM is upregulated in cutaneous lichen planus lesions suggesting a possible role in disease pathogenesis. Targeting CaM is expected to be a novel strategy for treatment of lichen planus.

Evaluation of PSP technique including dot peeling, subcision and intradermal injection of PRP in the treatment of atrophic post-acne scars.

BACKGROUND: Atrophic post-acne scars are common complications of acne. Many modalities are proposed, but each does not yield satisfactory clinical outcomes. To evaluate the therapeutic effect of PSP technique including dot peeling, subcision and intradermal injection of autologous platelet-rich plasma (PRP) for the treatment of atrophic post-acne scars. PATIENTS AND METHODS: Twenty patients with different types of atrophic acne scars on the face were included. All patients received PSP technique in the form of dot peeling, then after 2 weeks, subcision and intradermal PRP injection were done simultaneously. PSP technique was performed for each patient every month for 3 months. RESULTS: After 3 months of the last session, 30% of 20 patients had excellent improvement, 20% of patients had good improvement, 20% of patients had moderate improvement, and 30% of patients had mild improvement. There was statistically significant difference after treatment (p ≤ .001). Side effects were mild and tolerable and included erythema, ecchymosis, and hyperpigmentation. All types of scars showed significant improvement with no significant difference between them. CONCLUSION: PSP technique was found to be a safe and cost-effective treatment option for atrophic acne scars.

Evaluation of the efficacy of transdermal drug delivery of calcipotriol plus betamethasone versus tacrolimus in the treatment of vitiligo.

BACKGROUND: Vitiligo is a common pigmentary disorder affecting about 1% of the general population. There are numerous medical and surgical treatments. Microneedling is an evolving treatment technique for an expanding number of dermatologic conditions. It is used also to augment transdermal drug delivery through pores created in the stratum corneum. AIM: To evaluate the efficacy of microneedling with tacrolimus versus its efficacy with calcipotriol plus betamethasone in vitiligo treatment. METHODS: Twenty-five patients having vitiligo were selected and their symmetrical patches were divided into side A (right side) which received microneedling with dermapen and topical calcipotriol plus betamethasone and side B (left side) which received microneedling and topical tacrolimus. Every patient received a session every 2 weeks for a maximum 6 months (12 sessions) and follow-up for 3 months. Skin biopsies were taken before and after the treatment to evaluate the clinical results. RESULTS: On side A, 60% of the patients showed excellent improvement while 32% showed excellent response on side B. The mean percentage of improvement was significantly higher on side A than side B (P = 0.017* ). It was effective in the most resistant sites of vitiligo such as: elbows, knees, extremities, and acral area. Histopathological examination showed a significant expression of HMB45 on side A more than side B (P = 0.005* ). CONCLUSION: The combination of microneedling with calcipotriol plus betamethasone is more effective than its combination with tacrolimus. They are both effective in resistant sites. Both methods are safe, cheap, and good tolerated office techniques with minimal side effects.