Unravelling the immunobiology of innate lymphoid cells (ILCs): Implications in health and disease.

Innate lymphoid cells (ILCs), a growing class of immune cells, imitate the appearance and abilities of T cells. However, unlike T cells, ILCs lack acquired antigen receptors, and they also do not undergo clonal selection or proliferation in response to antigenic stimuli. Despite lacking antigen-specific receptors, ILCs respond quickly to signals from infected or damaged tissues and generate an array of cytokines that regulate the development of adaptive immune response. ILCs can be categorized into four types based on their signature cytokines and transcription factors: ILC1, ILC2, ILC3 (including Lymphoid Tissue inducer- LTi cells), and regulatory ILCs (ILCregs). ILCs play key functions in controlling and resolving inflammation, and variations in their proportion are linked to various pathological diseases including cancer, gastrointestinal, pulmonary, and skin diseases. We highlight current advancements in the biology and classification of ILCs in this review. Additionally, we provide a thorough overview of their contributions to several inflammatory bone-related pathologies, including osteoporosis, rheumatoid arthritis, periodontitis, and ankylosing spondylitis. Understanding the multiple functions of ILCs in both physiological and pathological conditions will further mobilize future research towards targeting ILCs for therapeutic purposes.

Morphology Transition with Temperature and its Effect on Optical Properties of Colloidal MoS2 Nanostructures.

Morphology plays a crucial role in determining the chemical and optical properties of nanomaterials due to confinement effects. We report the morphology transition of colloidal molybdenum disulfide (MoS2) nanostructures, synthesized by a one-pot heat-up method, from a mix of quantum dots (QDs) and nanosheets to predominantly nanorods by varying the synthesis reaction temperature from 90 to 160 °C. The stoichiometry and composition of the synthesized QDs, nanosheets, and nanorods were quantified to be MoS2 using energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy analyses. A nanostructure morphology transition due to variation in the reaction temperature resulted in a photoluminescence quantum yield enhancement from 0 to 4.4% on increasing the temperature from 90 to 120 °C. On further increase in the temperature to 160 °C, a decrease in the quantum yield to 3.06% is observed. Red-shifts of ≈18 and ≈140 nm in the emission maxima and absorption edge, respectively, are observed for the synthesized nanostructures with an increase in the reaction temperature from 90 to 160 °C. The change in the quantum yield is attributed to the change in shape and hence confinement of charge carriers. To the best of our knowledge, microscopic analysis of variation in shape and optical properties of colloidal MoS2 nanostructures with temperature, explained by a nonclassical growth mechanism is presented here for the first time.

One-Step Colloidal Synthesis of Non-Toxic Electroactive Carbon Dots with a Better Threshold Cytotoxicity and Cytocompatibility.

Carbon dots (CDs), because of their characteristic size (<10 nm) and highly fluorescent nature, can be internalized in biological cells or can be tagged to the key components of a living system. While these attributes can be potentially exploited for biomedical applications, the toxicity of CDs remains an important issue to be addressed. Both the synthesis approach and morphological attributes critically determine the dose-dependent toxicity and cytocompatibility of CDs. Against this perspective, we report herein a one-step colloidal synthesis of CDs using different reaction solvents that lead to the formation of three types of CDs (type I, type II, and type III CDs). The cytocompatibility and cellular uptake of CDs in human mesenchymal stem cells (hMSCs) are dependent on the nature of functionalization and concomitantly on the type of precursors. In particular, type I CDs are synthesized using citric acid, hexadecylamine, and octadecene that are immiscible in culture media. The type II CDs synthesized using citric acid and octadecene emit green fluorescence at a 488 nm excitation and were found to be agglomerated when internalized in hMSCs, whereas the type III CDs, synthesized using citric acid and deionized water, exhibit an agglomeration-free behavior. Further, type III CDs show a wide particle distribution, wide emission bandwidth range of 280-700 nm, threshold toxicity of 1 mg/mL, and good cytocompatibility with hMSCs, much better than those in the published reports. When benchmarked against commercial graphene quantum dots, the as-synthesized type III CDs have better electrical conductivity and cytocompatibility at a given dosage. Thus, the electroactive nature of synthesized type III CDs along with their inherent fluorescent property and less cytotoxicity would enable their potential applications in bio-imaging, directional lineage commitment, and cell-based therapy.

Bifidobacterium longum Ameliorates Ovariectomy-Induced Bone Loss via Enhancing Anti-Osteoclastogenic and Immunomodulatory Potential of Regulatory B Cells (Bregs).

Discoveries in the last few years have emphasized the existence of an enormous breadth of communication between osteo-immune systems. These discoveries fuel novel approaches for the treatment of several bone pathologies including osteoporosis. Bifidobacterium longum (BL) is a preferred probiotic of choice due to its varied immunomodulatory potential in alleviating various inflammatory diseases. Here, we evaluate the effect of BL in an ovariectomy (ovx)-induced post-menopausal osteoporotic mouse model. Our in vitro findings reveal that BL suppresses the differentiation and functional activity of RANKL-induced osteoclastogenesis in both mouse bone marrow cells and human PBMCs. Strikingly, BL-induced Bregs were found to be significantly more efficient in suppressing osteoclastogenesis and modulating Treg-Th17 cell balance with respect to control Bregs in vitro. Our in vivo µCT and bone mechanical strength data further confirm that BL supplementation significantly enhanced bone mass and bone strength, along with improving the bone microarchitecture in ovx mice. Remarkably, alterations in frequencies of CD19+CD1dhiCD5+IL-10+ Bregs, CD4+Foxp3+IL-10+ Tregs, and CD4+Rorγt+IL-17+ Th17 cells in distinct lymphoid organs along with serum-cytokine data (enhanced anti-osteoclastogenic cytokines IFN-γ and IL-10 and reduced osteoclastogenic-cytokines IL-6, IL-17, and TNF-α) strongly support the immunomodulatory potential of BL. Altogether, our findings establish a novel osteo-protective and immunomodulatory potential of BL in augmenting bone health under osteoporotic conditions.

Waste to white light: a sustainable method for converting biohazardous waste to broadband white LEDs.

The Covid-19 pandemic has generated a lot of non-degradable biohazardous plastic waste across the globe in the form of disposable surgical and N95 masks, gloves, face shields, syringes, bottles and plastic storage containers. In the present work we address this problem by recycling plastic waste to single system white light emitting carbon dots (CDs) using a pyrolytic method. The synthesized CDs have been embedded into a transparent polymer to form a carbon dot phosphor. This CD phosphor has a broad emission bandwidth of 205 nm and is stable against photo degradation for about a year. A white LED with CRI ∼70 and CIE co-ordinates of (0.25, 0.32) using the fabricated CD phosphor is reported. Further our phosphor is scalable and is environmentally sustainable, and will find wide application in next generation artificial lighting systems.

IL-21 plays an important role in modulating "Th17-Treg" cell axis in leprosy Type 1 reactions.

Leprosy type 1 reaction (T1R) is a cell-mediated inflammatory reaction which involves skin and peripheral nerves in leprosy. Lesions with T1R have higher production of IL-17 cytokine from CD4+ T cells along with lower TGF-ß producing FOXP3+ CD4+ Tregs. IL-21 is an important cytokine that promotes the development and stability of Th17 cells in an autocrine manner. It can play an important role in the pathogenesis of T1R in leprosy. However, the mechanism by which IL-21 influences the pathogenic progress of leprosy T1R remains poorly understood. In the present study, we evaluated the expression of IL-21 cytokine in skin lesions of both non-reactional (NR) and T1R via immuno-histochemistry and quantitative PCR (qPCR). Further, expression of various genes (IL-17A, IL-17F, TGF-ß, FOXP3, RORC and IL-21) was also measured by qPCR in cultured cells. We also analyzed the secretion of various cytokines such as of IL-21, IL-17A/F and TGF-ß in the culture supernatants by ELISA. In addition, differentiation of Th17 and Treg cells were studied in PBMC cultures after stimulation with Mycobacterium leprae sonicated antigens and rIL-21 for 48 hrs and the phenotypes of Th17 and Tregs were determined by flowcytometric analysis. Our results clearly indicate that IL-21+T cells were significantly higher in both peripheral blood and skin lesions of T1R as compared to NR patients. Moreover, we observed that recombinant IL-21 cytokine inhibited TGF-ß producing Treg cells differentiation along with up-regulating Th17 cells under in-vitro conditions. The gene expression of IL-21 was significantly negatively correlated with Treg and positively correlated with Th17 cell markers in T1R patients. Our results suggested that IL-21 promotes T1R mediated inflammation via modulating the balance of Th17 and Treg cell populations.

COVID-19: Immunology, Immunopathogenesis and Potential Therapies.

The Coronavirus Disease-2019 (COVID-19) imposed public health emergency and affected millions of people around the globe. As of January 2021, 100 million confirmed cases of COVID-19 along with more than 2 million deaths were reported worldwide. SARS-CoV-2 infection causes excessive production of pro-inflammatory cytokines thereby leading to the development of "Cytokine Storm Syndrome." This condition results in uncontrollable inflammation that further imposes multiple-organ-failure eventually leading to death. SARS-CoV-2 induces unrestrained innate immune response and impairs adaptive immune responses thereby causing tissue damage. Thus, understanding the foremost features and evolution of innate and adaptive immunity to SARS-CoV-2 is crucial in anticipating COVID-19 outcomes and in developing effective strategies to control the viral spread. In the present review, we exhaustively discuss the sequential key immunological events that occur during SARS-CoV-2 infection and are involved in the immunopathogenesis of COVID-19. In addition to this, we also highlight various therapeutic options already in use such as immunosuppressive drugs, plasma therapy and intravenous immunoglobulins along with various novel potent therapeutic options that should be considered in managing COVID-19 infection such as traditional medicines and probiotics.

Regulatory B Cells (Bregs) Inhibit Osteoclastogenesis and Play a Potential Role in Ameliorating Ovariectomy-Induced Bone Loss.

Increasing evidence in recent years has suggested that regulatory B cells (Bregs) are one of the crucial modulators in various inflammatory disease conditions. However, no study to date has investigated the significance of Bregs in modulating osteoclastogenesis. To the best of our knowledge, in the present study, we for the first time examined the anti-osteoclastogenic potential of Bregs under in vitro conditions and observed that Bregs suppress RANKL-induced osteoclastogenesis in a dose-dependent manner. We further elucidated the mechanism behind the observed suppression of osteoclasts differentiation via Bregs. Our results clearly suggested that the observed anti-osteoclastogenic property of Bregs is mediated via the production of IL-10 cytokine. Next, we explored whether Bregs have any role in mediating inflammatory bone loss under post-menopausal osteoporotic conditions in ovx mice. Remarkably, our in vivo data clearly suggest that the frequencies of both CD19+IL-10+ Bregs and CD19+CD1dhiCD5+IL-10+ "B10" Bregs were significantly reduced in case of osteoporotic mice model. Moreover, we also found a significant reduction in serum IL-10 cytokine levels in osteoporotic mice, thereby further supporting our observations. Taken together, the present study for the first time establishes the direct role of regulatory B cells in modulating osteoclastogenesis in vitro. Further, our in vivo data suggest that modulations in the percentage of Bregs population along with its reduced potential to produce IL-10 might further exacerbate the observed bone loss in ovx mice.

Excellent color rendering index single system white light emitting carbon dots for next generation lighting devices.

Recently, quantum dots (QDs) are finding enormous application in white light emitting diodes (WLEDs) and WLEDs with high color rendition are in high demand. QD-WLEDs use different color (Red, Blue, Green) emitting QDs to obtain white light. Use of different color emitting QDs affect purity of white light due to self-absorption losses and QD degradation, in the long run affecting color rendering index (CRI) of WLEDs. Herein, we report low cost, environment friendly, open air atmosphere synthesis of single system white light emitting carbon dots (CDs) with broad emission bandwidth ranging 116 -143 nm and quantum yields (QY) ~ 5 - 13 % in colloidal state by modifying CD surface. Furthermore, carbon dot polymer phosphor (CD-PDMS phosphor) is fabricated which emits white light under UV illumination with a record emission bandwidth of ~ 154 nm and QY ~ 16 % in solid state. Moreover, CD-PDMS phosphor exhibit excellent color rendering index (CRI) ~ 96, the highest reported so far with CIE co-ordinates (0.31, 0.33) that are quite akin to pure white light. Such high performances are achieved due to high quality of CDs and CD-PDMS polymer phosphors by precise control in passivation/functionalization of nanoparticle surface. This work will set platform for the application of CD-phosphor based WLEDs in lighting systems.

Phytotherapy for treatment of cytokine storm in COVID-19.

In 2020, a novel strain of coronavirus (COVID-19) has led to a significant morbidity and mortality worldwide. As of the date of this writing, a total of 116 M cases has been diagnosed worldwide leading to 2.5 M deaths. The number of mortalities is directly correlated with the rise of innate immune cells (especially macrophages) in the lungs that secrete inflammatory cytokines (IL-1ß and IL-6) leading to the development of "Cytokine Storm Syndrome" (CSS), multi-organ-failure and death. Given that currently the treatment of this condition is rare and release of effective vaccine might be months away, here, we review the plants and their pharmacologically active-compounds as potential phytopharmaceuticals for the virus induced inflammatory response. Experimental validation of the effectiveness of these natural compounds to prevent or reduce the cytokine storm might be beneficial as an adjunct treatment of SARS-CoV-2.

Lactobacillus rhamnosus attenuates bone loss and maintains bone health by skewing Treg-Th17 cell balance in Ovx mice.

Osteoporosis is a systemic-skeletal disorder characterized by enhanced fragility of bones leading to increased rates of fractures and morbidity in large number of populations. Probiotics are known to be involved in management of various-inflammatory diseases including osteoporosis. But no study till date had delineated the immunomodulatory potential of Lactobacillus rhamnosus (LR) in bone-health. In the present study, we examined the effect of probiotic-LR on bone-health in ovariectomy (Ovx) induced postmenopausal mice model. In the present study, we for the first time report that LR inhibits osteoclastogenesis and modulates differentiation of Treg-Th17 cells under in vitro conditions. We further observed that LR attenuates bone loss under in vivo conditions in Ovx mice. Both the cortical and trabecular bone-content of Ovx+LR treated group was significantly higher than Ovx-group. Remarkably, the percentage of osteoclastogenic CD4+Rorγt+Th17 cells at distinct immunological sites such as BM, spleen, LN and PP were significantly reduced, whereas the percentage of anti-osteoclastogenic CD4+Foxp3+Tregs and CD8+Foxp3+Tregs were significantly enhanced in LR-treated group thereby resulting in inhibition of bone loss. The osteoprotective role of LR was further supported by serum cytokine data with a significant reduction in osteoclastogenic cytokines (IL-6, IL-17 and TNF-α) along with enhancement in anti-osteoclastogenic cytokines (IL-4, IL-10, IFN-γ) in LR treated-group. Altogether, the present study for the first time establishes the osteoprotective role of LR on bone health, thus highlighting the immunomodulatory potential of LR in the treatment and management of various bone related diseases including osteoporosis.

"Osteomicrobiology": The Nexus Between Bone and Bugs.

A growing body of scientific evidence supports the notion that gut microbiota plays a key role in the regulation of various physiological and pathological processes related to human health. Recent findings have now established that gut microbiota also contributes to the regulation of bone homeostasis. Studies on animal models have unraveled various underlying mechanisms responsible for gut microbiota-mediated bone regulation. Normal gut microbiota is thus required for the maintenance of bone homeostasis. However, dysbiosis of gut microbiota communities is reported to be associated with several bone-related ailments such as osteoporosis, rheumatoid arthritis, osteoarthritis, and periodontitis. Dietary interventions in the form of probiotics, prebiotics, synbiotics, and postbiotics have been reported in restoring the dysbiotic gut microbiota composition and thus could provide various health benefits to the host including bone health. These dietary interventions prevent bone loss through several mechanisms and thus could act as potential therapies for the treatment of bone pathologies. In the present review, we summarize the current knowledge of how gut microbiota and its derived microbial compounds are associated with bone metabolism and their roles in ameliorating bone health. In addition to this, we also highlight the role of various dietary supplements like probiotics, prebiotics, synbiotics, and postbiotics as promising microbiota targeted interventions with the clinical application for leveraging treatment modalities in various inflammatory bone pathologies.

Highly Stable White-Light-Emitting Carbon Dot Synthesis Using a Non-coordinating Solvent.

In this article, synthesis of white-light-emitting, highly stable carbon dots (CDs) using a colloidal synthesis technique is reported. It has been observed that the use of a non-coordinating solvent plays a vital role in the successful fabrication of highly stable CDs. Dilution-independent emissive behavior in CDs is achieved. Excitation-energy-dependent emissive behavior is observed in CDs. However, by surface passivating the CD core by using hexadecylamine (HDA), excitation wavelength dependence of emission is successfully minimized. Surface-functionalized CDs (SFCDs) show blue to green light tunable emission with the change in synthesis conditions. HDA also plays an important role in achieving dilution-independent emission in SFCDs. Furthermore, the carbon dots synthesized are highly inert, and their emission spectra are unaffected on exposure to an open atmosphere for as long as 9 days. A new class of highly crystalline carbon dots called "carbon onion rings" is reported.

A model to aid in the prediction of discharge location for stroke rehabilitation patients.

OBJECTIVE: To determine which demographic and medical factors recorded on admission to a rehabilitation unit best predict discharge accommodation outcomes. DESIGN: Retrospective chart review. SETTING: Inpatient rehabilitation unit in an academic hospital in southwestern Ontario, Canada. PARTICIPANTS: One hundred four stroke patients (54 women, 50 men; mean age, 72.0y) admitted to the rehabilitation unit over a 4-year period. INTERVENTIONS: All patients underwent evaluations by the physical therapy, occupational therapy, social work, speech pathology, and psychology departments. Patients were divided into 2 groups: (1) no change in premorbid accommodation and (2) change in premorbid accommodation. MAIN OUTCOME MEASURES: Demographic, clinical, and housing information (premorbid, discharge) and functional data (FIM trade mark instrument, Chedoke-McMaster Stroke Assessment [CMSA] Impairment Inventory, Berg Balance Scale [BBS]) were recorded for each patient. RESULTS: Of 104 patients, 24 were discharged with a change in premorbid accommodation. Change in discharge location was significantly associated with age, gender, and the presence of premorbid social support (P<.01), but not with type of premorbid living arrangement. Statistically significant differences were noted between total FIM scores (P<.001), BBS scores (P<.001), and the postural component of the CMSA Impairment Inventory (P<.03). A logistic regression model, predicting 67% of the variance, was created to predict discharge accommodations. CONCLUSIONS: Patients admitted to the rehabilitation unit can be scored to obtain their predicted chance of being discharged with a change from their premorbid accommodations. The equation is relatively easy to calculate and is based on data that are commonly collected in rehabilitation.

The incidence and consequences of falls in stroke patients during inpatient rehabilitation: factors associated with high risk.

OBJECTIVES: To determine the incidence of falls on a stroke rehabilitation unit; to assess the frequency and nature of injuries; and to identify risk factors predictive of falls, functional outcomes, and impairments. DESIGN: Retrospective cohort study. SETTING: An inpatient stroke rehabilitation unit. PARTICIPANTS: Two hundred thirty-eight consecutive stroke patient admissions. INTERVENTIONS: Incident reports completed on patients who experienced a fall while on the unit were reviewed and resultant injuries categorized (abrasions, lacerations, fractures). MAIN OUTCOME MEASURES: Stroke impairments and admission functional assessments, FIM instrument, Berg Balance Scale (BBS), and Chedoke-McMaster (CM) Stroke Impairment Inventory of fallers were compared with nonfallers. RESULTS: Of the 238 patients, 88 (37%) experienced at least 1 fall, and almost half of these (45 patients [19%]) experienced at least 2 falls. A total of 180 falls were reported over the 5-year period. Of the 180 reported falls, 33% occurred when patients were using their wheelchairs. Injuries occurred in 22% of the reported falls. These consisted of contusions (49%) and abrasions (41%), primarily of the upper (30.8%) and lower (25.6%) extremities. Only 1 fracture was reported. Fallers tended to have lower admission BBS scores (50% of patients with a score <30 fell vs 18% with a score >30, P <.01) and a lower score on the admission arm, leg, and foot components of the CM (P <.05). Patients who fell were also more likely to be apraxic (P <.014) and suffer from cognitive deficits (P <.01). Repeat fallers had lower admission FIM scores (P <.01) when compared with nonfallers. CONCLUSION: Although patients undergoing stroke rehabilitation experienced a significant number of falls, the incidence of serious injury was small. Patients who experienced at least 1 fall had significantly lower BBS, FIM, and CM arm, leg, and foot scores compared with nonfallers. These data suggest that groups of stroke patients who are at risk for falls within the rehabilitation setting can be identified by using a variety of impairment and functional assessments. This information may be potentially useful for designing interventions directed at reducing fall frequency among stroke survivors.